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Visit www.corning.com/lifesciences for additional product and technical information. A ADME/Tox Product Selection Guide Corning® Gentest TM Reagents and Corning Gentest SM Contract Research Services

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Page 1: ADME/Tox Product Selection Guide · 459011 BSEP vesicle assay kit N/A – Up to 200 assays Corning Gentest™ Transporter Kits Corning transporter membrane and vesicle kits provide

Visit www.corning.com/lifesciences for additional product and technical information.A

ADME/Tox Product Selection GuideCorning® GentestTM Reagents and Corning GentestSM Contract Research Services

Page 2: ADME/Tox Product Selection Guide · 459011 BSEP vesicle assay kit N/A – Up to 200 assays Corning Gentest™ Transporter Kits Corning transporter membrane and vesicle kits provide

Visit www.corning.com/lifesciences for additional product and technical information.

IntroductionCORN I NG® GENTEST™ ADME/ TOX PRODUCTS

Corning Life Sciences is dedicated to the development of novel assay solutions for ADME/Tox properties, including products and research services for drug metabolism, transport, solubility, protein binding, and toxicity. Our scientists are internationally recognized as leaders and innovators in developing drug metabolism and drug interaction assay tools. This demon strated commitment to research has been rewarded by the receipt of several competitive NIH grants. The results and applications of our research are reported in peer reviewed journals and at international symposia by our scientists, colleagues, and customers interested in xenobiotic metabolism.

Founded in 1983, Gentest products and services initially focused on the use of cultured human cells in GLP genotoxicity assays. In 1985, the company expanded research activities into the area of xenobiotic metabolism by developing cytochrome P450 cDNA-expression approaches. This led to the first commercial offering of cDNA-expressed human cytochrome P450 enzymes in 1990. Since that time, the range of Corning Gentest products, human cytochrome P450 forms and other xenobiotic-metabolizing enzymes, as well as the human and animal tissue products, has increased dramatically.

In addition to supplying cDNA-expressed cytochrome P450 and other drug metabolizing enzymes, Corning Life Sciences produces and distributes human and animal liver microsomes; cryopreserved hepatocytes; novel cytochrome P450 metabolites, substrates, and chemical inhibitors; ABC transporter vesicles and SLC transporter-expressing cells; and filter-permeable support systems for drug transport and permeability (i.e., Caco-2 and PAMPA).

CORN I NG GENTEST SM CONTRACT RESEARCH SERVICES

Corning Gentest Contract Research Services have been serving customers for more than 20 years, supporting drug discovery and development programs, from secondary screens to post-marketing commitment. Our Study Directors are highly skilled scientists with an in-depth knowledge of absorption, transport, metabolism, and toxicity. This expertise enables Corning Life Sciences Study Directors to partner with you to develop and deliver a broad range of in vitro ADME/Tox studies customized to meet your discovery and development project needs. We ensure the highest level of quality and adhere to current regulatory requirements and applicable regulatory agency guidance documents.

Utilizing state-of-the art materials, techniques, and equipment, Corning Life Sciences is ideally suited to assist you in screening for viable drug candidates during drug discovery or to prepare regulatory agency submission-quality reports for your drug development compounds. Let our team of experts take you to the next level with studies designed to predict drug-drug interactions and human pharmaco kinetics using the innovative Corning Gentest products, cell models, and methodologies.

Page 3: ADME/Tox Product Selection Guide · 459011 BSEP vesicle assay kit N/A – Up to 200 assays Corning Gentest™ Transporter Kits Corning transporter membrane and vesicle kits provide

1

Ordering and Contact Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2

Absorption/Transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3

ABC and SLC Transporter Model Systems . . . . . . . . . . . . . . . . . . . . . .3

Chemicals for Measuring Transporter Activity . . . . . . . . . . . . . . . . .5

Cell Culture and Multiwell Filter Permeable Support Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5

Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Recombinant Metabolic Enzymes, Cofactors, and Buffers . . . . . 8

Chemical Substrates, Inhibitors, Metabolite Standards, and Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Tissue Fractions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Corning Gentest Human Cryohepatocytes . . . . . . . . . . . . . . . . . . 15

Custom Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Contract Research Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

ADME/Tox

Page 4: ADME/Tox Product Selection Guide · 459011 BSEP vesicle assay kit N/A – Up to 200 assays Corning Gentest™ Transporter Kits Corning transporter membrane and vesicle kits provide

Visit www.corning.com/lifesciences for additional product and technical information.2

Ordering and Contact Information

Corning® ADME/Tox Products:

Customer Service

To place your order call Customer Service:

Francet 0800 916 882f 0800 918 636

Germanyt 0800 101 1153f 0800 101 2427

The Netherlandst +31 20 655 79 28f +31 20 659 76 73

United Kingdomt 0800 376 8660f 0800 279 1117

All Other European Countriest +31 20 659 60 51f +31 20 659 76 73

Email direct: [email protected] distribution: [email protected]: visit www.corning.com/lifesciences/media

Scientific Support

Email: [email protected]

Francet 0800 916 882

Germanyt 0800 101 1153

The Netherlandst +31 20 655 79 28

United Kingdomt 0800 376 8660

All Other European Countriest +31 20 659 60 51

Corning GentestSM Contract Research Services

To discuss and order Corning Gentest Contract Research Services, contact Corning Life Sciences at 781.938.2546 or e-mail: [email protected].

Online Shopping

Visit www.corning.com/lifesciences and open an account to order products online.

Delivery and Product Satisfaction on Direct Orders

◗◗ Products will be replaced at no cost, if the product does not conform to the accompanying analytical data report.

◗◗ Products will be replaced at no cost, if shipment is incomplete or damaged. Report incomplete shipments within 5 days, damaged shipments within 48 hours.

◗◗ Returned goods authorization (RGA) number, assigned by a Customer Service Representative, is required prior to all product returns.

◗◗ Appropriate shipping documents, cartons, and packing materials are required for all product returns.

◗◗ No product may be returned for credit or replacement after 20 days.

HepatoLink

HepatoLink® is the Corning Life Sciences immediate response system providing researchers with instant notification when Corning Gentest hepatocyte products are available. For your convenience, select a preferred contact method—email, phone, and/or SMS text alerts. Upon registration, you will be sent donor chara cteriza tion data when a new lot becomes available. You can register online at www.corning.com /lifesciences/hepatolink. Place your order directly through Corning's online system. If you have any questions regarding Corning's program or your participation, contact us at 978.442.2200 or email [email protected].

All Corning Gentest cryohepatocyte orders must be lot specific. Each lot number corresponds with a specific donor and must be included with your order. An up-to-date listing of Corning Gentest human cryohepatocyte donors with donor demographics, donor history, and characterization data is maintained at www.corning.com/lifesciences/admetox.

Use of Genetically Modified Microorganisms (GMMO)

Information for European Customers: Corning TransportoCells™ products are considered genetically modified microorganisms as described in Corning Life Sciences technical literature. As a condition of sale, use of these products must be in accordance with all applicable local guidelines on the contained use of genetically modified microorganisms, including the Directive 2009/41/EC of the European Parliament and of the Council.

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3 For more specific information on claims, visit the Certificates page at www.corning.com/lifesciences.

ABC AN D SLC TRANSPORTER MODEL SYSTEMS

Corning offers a range of products and assay solutions for the assessment of absorption properties and transporter studies.

Corning® Gentest™ transporter products are in vitro models designed for use in drug transport studies, and include ABC transporter inside-out vesicles and SLC transporter expressing cells. These recombinant products are designed for high throughput screening use in ADME studies. Corning also offers transporter-qualified primary hepatocytes that can be used in suspension or monolayer assays. These native cells models provide a more accurate prediction of in vivo activity than most standard recombinant models.

Corning TransportoCells™ Cryopreserved SLC Transporter Cells

Corning SLC TransportoCells products are high performance mammalian cells transiently over-expressing a single human SLC transporter protein. They are ideal cell-based models for studying transporter activities in reaction phenotyping, drug-drug interaction, and drug clearance studies.

◗◗ Cryopreserved, single-use HEK-293 cells expressing a single transporter

◗◗ High and robust signal-to-noise ratio (S:N ≥10)

◗◗ Direct measurement of transporter-mediated drug uptake

◗◗ Cells can be thawed, plated, and assayed in just 24 hours

◗◗ Use in drug uptake assays for radiolabeled or non-radiolabeled compounds

Absorption/Transport

OATP

PEPT

OAT/OCT

NTCP

H+

Na+ S

SS

S

Cat. No. Description Full Name Gene Accession Number Number of Cells

354851 OATP1B3/SLCO1B3 Organic anion-transporting polypeptide 1B3 NM_019844 ≥10 million

354852 OCT1/SLC22A1 Organic cation transporter 1 NM_003057 ≥10 million

354853 OCT2/SLC22A2 Organic cation transporter 2 NM_003058 ≥10 million

354854 Vector Control N/A N/A ≥10 million

354855 MATE1/SLC47A1 Multidrug and Toxin Extrusion transporter 1 NM_018242 ≥10 million

354856 MATE2-K/SLC47A2 Multidrug and Toxin Extrusion transporter 2-K NM_001099646 ≥10 million

354857 OAT1/SLC22A6 Organic anion transporter 1 NM_004790 ≥10 million

354858 OAT3/SLC22A8 Organic anion transporter 3 NM_004254 ≥10 million

354859 OATP1B1*1a/ Organic anion-transporting polypeptide 1B1, NM_006446.4 ≥10 million SLCO1B1*1a Wild Type (388A)

354860 PEPT1/SLC15A1 Peptide transporter 1 NM_005073 ≥10 million

354861 PEPT2/SLC15A2 Peptide transporter 2 NM_021082 ≥10 million

354862 OATP2B1/SLCO2B1 Organic anion-transporting polypeptide 2B1 NM_007256 ≥10 million

354863 OATP1A2/SLCO1A2 Organic anion-transporting polypeptide 1A2 NM_021094 ≥10 million

354864 NTCP/SLC10A1 Na+-taurocholate cotransporting polypeptide NM_003049 ≥10 million

354866 OCTN2 Organic cation/carnitine transporter 2 NM_003060 ≥10 million

354867 OAT2 Organic anion transporter 2 NM_006672 ≥10 million

354868 OAT4 Organic anion transporter 4 NM_018484 ≥10 million

354841 Rat Oatp1b2 Rat organic anion-transporting polypeptide 1b2 NM_031650 ≥10 million

354842 Dog Oatp1b4 Dog organic anion-transporting polypeptide 1b4 GQ497899 ≥10 million

354843 Monkey Oatp1b1 Monkey organic anion-transporting polypeptide 1b1 JX866725 ≥10 million

354878 OATP1B1*5 Organic anion-transporting polypeptide 1B1 SNP NM_006446.4 with ≥10 million (521T>C) 521T>C

354879 OATP1B1*15 Organic anion-transporting polypeptide 1B1 SNPs NM_006446.4 with ≥10 million (388A>G, 521T>C) 388A>G, 521T>C

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Visit www.corning.com/lifesciences for additional product and technical information.4

Corning® TransportoCells™ HEK293-derived ABC Transporter Vesicles

Corning TransportoCells HEK293-derived ABC transporter vesicles express more human-like transporter proteins within the human cellular membrane. These HEK membrane vesicles have demonstrated a significantly higher uptake activity and lower background as compared with traditional insect cell-derived vesicles. The validated vesicle model could potentially improve in vitro to in vivo prediction because of the more in vivo-like recombinant proteins and membrane composition. The products can be used for drug transporter phenotyping, drug-drug interaction and toxicity studies, drug clearance prediction, and mechanistic studies of drug transport.

◗◗ Contain more in vivo-like recombinant proteins and membrane composition, thus providing the potential for a better in vitro to in vivo correlation

◗◗ Demonstrate a robust dynamic range with significantly higher uptake activity and lower background than insect cell expression systems

◗◗ Has been fully validated for substrate specificity, transporter kinetics, and inhibition profiles

◗◗ Support the USFDA, EMA, and ITC recommendations for the identification of drug transporters and transporter drug-drug interaction studies

Gene Protein Cat. No. Description Accession No. Concentration Qty

453800 HEK293-derived negative control vesicle N/A 5 mg/mL 0.5 mL

453801 HEK293-derived Human MDR1/P-gp vesicles NM_000927 5 mg/mL 0.5 mL

453802 HEK293-derived human BSEP vesicles NM_003742 5 mg/mL 0.5 mL

453803 HEK293-derived human MRP2 vesicles NM_000392 5 mg/mL 0.5 mL

453804 HEK293-derived human BCRP vesicles NM_004827 5 mg/mL 0.5 mL

453805 HEK293-derived human MRP3 vesicles NM_003786 5 mg/mL 0.5 mL

453806 HEK293-derived human MRP4 vesicles NM_005845 5 mg/mL 0.5 mL

459010 MRP/BCRP vesicle assay kit N/A – Up to 200 assays

459011 BSEP vesicle assay kit N/A – Up to 200 assays

Corning Gentest™ Transporter Kits

Corning transporter membrane and vesicle kits provide convenience and reduce the time needed for reagent preparation. The ATPase kit contains all the necessary buffers and chemicals for performing five 96-well microplate assays. The BSEP and BCRP/MRP kits contain all necessary buffers and chemi-cals for performing 200 assays. However, these kits do not include vesical or membrane preps.

Cat. No. Description Qty

459010 Corning Gentest MRP/BCRP vesicle assay kit 1 kit Kit contains reagents for 200 assays (assay uptake buffer, 10X wash buffer, 200 mM ATP,

200 mM AMP, 300mM GSH, MRP3 substrate, BCRP substrate, MRP2/MRP3 fluorescent substrate, MRP1/MRP2 substrate).

459011 Corning Gentest BSEP vesicle assay kit 1 kit Kit contains reagents for 200 assays (assay uptake buffer, 10X wash buffer, 200 mM ATP,

200 mM AMP, BSEP substrate, blocking buffer [50X]).

Corning Gentest Transporter-qualified Human Cryohepatocytes

Corning Gentest transporter-qualified human cryopreserved hepatocytes are ideal for in vivo-like screening of drug compounds for hepatic transporter uptake activity, as well as for investigating transporter involved drug-drug interaction. Every lot is extensively tested, pre-qualified for transporter activity using 3H-Estrone-3-sulfate, 3H-TCA, and 3C-TEA as probe substrates for hOATP, hNTCP, and hOCT1, respectively. These hepatocytes can also be used in metabolic stability and drug clearance studies.

For SLC transporter-specific characterization, such as evaluating a drug candidate’s affinity to a specific SLC transporter, follow up your testing with Corning SLC TransportoCells™ products.

To view an up-to-date listing of Corning Gentest transporter-qualified human cryopreserved hepatocyte donors with donor demographics, donor history, and characterization data, contact [email protected].

Cat. No. Description Cells/Vial Qty/Pk

454541 Corning Gentest plateable transporter-qualified human cryohepatocytes ≥5 million cells 1.5 mL

Inside Out ATP

ADP + P

DrugS

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5 For more specific information on claims, visit the Certificates page at www.corning.com/lifesciences.

CH EMICALS FOR MEASU RI NG TRANSPORTER ACTIVITY

CLF is a fluorescein-labeled bile acid with biological behavior closely resembling naturally occurring cholyl glycine. CLF is secreted into bile canaliculi by the bile salt export pump (BSEP) transporter.

Cat. No. Description Qty/Pk

451041 CLF (Choly-lysyl-fluorescein) 1 mg

CELL CU LTU RE AN D MU LTIWELL FI LTER PERMEABLE SU PPORT SYSTEMS

Corning® Gentest™ Pre-coated PAMPA Plate SystemCat. No. Description Qty/Cs

353015 Corning Gentest PAMPA 96-well pre-coated filter plate, individually packaged 5 with a 96-well microassay receiver plate

Corning BioCoat™ HTS Caco-2 Assay System

System includes:

◗◗ Corning BioCoat 1.0 µm Fibrillar Collagen-coated 24 multiwell filter permeable support plate and single-well feeder tray

◗◗ Corning Intestinal epithelium seeding medium – 250 mL

◗◗ Corning Intestinal epithelium differentiation medium – 250 mL

◗◗ Corning Mito+ serum extender – 0.5 mL

◗◗ Complete protocol

Cat. No. Description Qty/Cs

354801 Corning BioCoat HTS Caco-2 assay system, 1 kit 1

354802 Corning BioCoat HTS Caco-2 assay system, 5 kits 5

Corning BioCoat Fibrillar Collagen 24 Multiwell Permeable Support System

Corning BioCoat 1.0 µm Fibrillar Collagen-coated 24 multiwell filter permeable support plate and single-well feeder tray

Cat. No. Description Qty/Cs

354803 Corning BioCoat Fibrillar Collagen 24 multiwell permeable support system, 1 kit 1

354804 Corning BioCoat Fibrillar Collagen 24 multiwell permeable support system, 5 kits 5

Falcon® 24 Multiwell Permeable Support System

System includes:

◗◗ Falcon 1.0 µm 24 multiwell filter permeable support plate and single-well feeder tray with lid

NOTE: Companion receiver plate for drug transport studies must be ordered separately (Cat. No. 353047 or 353935)

Cat. No. Description Qty/Cs

351180 Falcon 24 multiwell permeable support system, 1 kit 1

351181 Falcon 24 multiwell permeable support system, 5 kits 5

Companion Products for Falcon 24 Multiwell Permeable Support Systems

Cat. No. Description Qty/Cs

353047 Falcon 24-well receiver plates and lids 50 (For use as multiwell feeder trays or drug transport studies)

353935 Falcon 24-well receiver plates and lids 60 (RS*) (For use as multiwell feeder trays or drug transport studies)

351186 Falcon single-well feeder tray and lid 5 *RS = Packaged in ready-stack trays.

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Visit www.corning.com/lifesciences for additional product and technical information.6

HTS Transwell® 96-well Permeable Support System

System includes:

◗◗ HTS Transwell 96-well permeable support system, 1.0 µm polyester (PET) membrane, reservoir, and receiver plates with 2 lids

Cat. No. Description Qty/Cs

3380 HTS Transwell 96-well permeable support system, 1 kit 1

3392 HTS Transwell 96-well permeable support system, 5 kits 5

Falcon® 96 Multiwell Permeable Support Systems

System includes:

◗◗ Falcon 1.0 µm 96 multiwell filter permeable support plates and single-well feeder tray with baffle and lid

NOTE: Companion receiver plate for drug transport studies must be ordered separately (Cat. No. 353925).

Cat. No. Description Qty/Cs

351130 Falcon 96 multiwell permeable support system, single well, 1 kit 1

351131 Falcon 96 multiwell permeable support system, single well, 5 kits 5

System includes:

◗◗ Falcon 1.0 µm 96 multiwell filter permeable support plates and companion 96 square-well, angled-bottom plates and lids

NOTE: Companion feeder tray with baffle and lid for drug transport studies must be ordered separately (Cat. No. 353924).

Cat. No. Description Qty/Cs

353938 Falcon 96 multiwell permeable support system, square well, 5 kits 5

Companion Products for Falcon 96 Multiwell Permeable Support Systems

Cat. No. Description Qty/Cs

353925 Falcon 96 square-well, angled-bottom receiver plates and lids 5

353924 Falcon single-well feeder tray with baffle and lid 5

Transwell Individual Cell Culture Permeable Supports

Polycarbonate Membrane, 0.4 µm pore size, 1.0 x 108 pores/cm2 Cat. No. Description Qty/Pk Qty/Cs

3412 6-well 6 24

3401 12-well 12 48

3413 24-well 12 48

Polyester Membrane, 0.4 µm pore size, 4.0 x 106 pores/cm2

3450 6-well 1 48

3460 12-well 12 483470 24-well 12 48

Falcon Individual Cell Culture Permeable Supports

Transparent PET Membrane, 0.4 µm pore size, 1.6 x 106 pores/cm2

Cat. No. Description Qty/Pk Qty/Cs

353090 6-well 1 48

353180 12-well 1 48

353095 24-well 1 48

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7 For more specific information on claims, visit the Certificates page at www.corning.com/lifesciences.

Transparent PET Membrane, 1.0 µm pore size, 1.6 x 106 pores/cm2

Cat. No. Description Qty/Pk Qty/Cs

353102 6-well 1 48

353103 12-well 1 48

353104 24-well 1 48

High Density, Translucent PET Membrane, 0.4 µm pore size, 1.0 x 108 pores/cm2

353493 6-well 1 48

353494 12-well 1 48

353495 24-well 1 48

Corning® BioCoat™ Cell Culture Deep Well PlateCat. No. Description Qty/Pk Qty/Cs

355467 6-well 1 4

Falcon® Cell Culture Permeable Support Companion PlatesCat. No. Description Qty/Pk Qty/Cs

353502 6-well 1 50

353503 12-well 1 50

353504 24-well 1 50

For more information on Corning cell culture, Transwell® permeable support inserts, Falcon® cell culture and multiwell permeable support inserts, visit www.corning.com/lifesciences.

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RECOMBI NANT METABOLIC ENZYMES, COFACTORS, AN D BU FFERS

Corning® Supersomes™ Enzymes are recombinant enzyme products and recognized worldwide as the industry gold standard. These enzymes are prepared from baculovirus-transfected insect cells with very high levels of catalytic activities (typically 6-fold higher than an average HLM sample). This is ideal for screening high throughput drug interactions, studying slowly metabolized chemicals, or manufacturing large-scale production of metabolites for structural identification.

Corning offers more than 40 different human and animal P450 isoforms, many with or without NADPH reductase. Additionally, Corning offers wide range of non-P450 metabolic enzymes, including UDP-glucuronosyl transferases (UGTs), flavin-containing monooxygenases (FMOs), monoamine oxidases (MAOs), soluble N-Acetyltransferases (NATs), and carboxylesterases (CESs). For many of the recombinant enzyme products, side-by-side comparisons of the catalytic activity with pooled human liver microsomes (HLMs) have been performed and the data are available by email to [email protected].

Key Benefits

◗◗ Wide-range selection of high quality metabolism enzymes

◗◗ Higher catalytic activities than the native enzymes from human liver and other organs, with comparable Km

◗◗ Accepted industry gold standard recombinant enzyme system, with large number of peer-reviewed publications

◗◗ Preferred enzymes for generating data to use with the Simcyp computational model

◗◗ Supports essential assays such as reaction phenotyping, metabolic stability, and enzyme inhibition required for FDA new drug registration and other pharmacokinetic studies that are appropriate for evaluating pro-drugs and CYP or non-CYP pathways of elimination.

Corning® Supersomes™ Metabolic Enzymes

Human P450 EnzymesCat. No. Description P450 Content (nmol) Qty (mL)

456211 Human CYP1A1 + reductase 0.5 0.5

456203 Human CYP1A2 + reductase 0.5 0.5

456220 Human CYP1B1 + reductase 0.5 0.5

456204 Human CYP2A6 + reductase 1 0.5

456254 Human CYP2A6 + reductase + b5 0.5 0.5

456210 Human CYP2B6 + reductase 0.5 0.5

456255 Human CYP2B6 + reductase + b5 0.5 0.5

456222 Human CYP2C18 + reductase 0.5 0.5

456219 Human CYP2C19 + reductase 0.5 0.5

456259 Human CYP2C19 + reductase + b5 0.5 0.5

456212 Human CYP2C8 + reductase 1 0.5

456252 Human CYP2C8 + reductase + b5 0.5 0.5

456218 Human CYP2C9*1 (Arg144) + reductase 1 0.5

456258 Human CYP2C9*1 (Arg144) + reductase + b5 0.5 0.5

456209 Human CYP2C9*2 (Cys144) + reductase allelic variant 1 0.5

456242 Human CYP2C9*3 (Leu359) + reductase allelic variant 1 0.5

456217 Human CYP2D6*1 (Val374) + reductase 0.5 0.5

456206 Human CYP2E1 + reductase + b5 1 0.5

456264 Human CYP2J2 + reductase + b5 0.5 0.5

456207 Human CYP3A4 + reductase 1 0.5

456202 Human CYP3A4 + reductase + b5 0.5 0.5

456235 Human CYP3A5 + reductase 1 0.5

456256 Human CYP3A5 + reductase + b5 0.5 0.5

Metabolism

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9 For more specific information on claims, visit the Certificates page at www.corning.com/lifesciences.

Human P450 Enzymes (Continued)

Cat. No. Description P450 Content (nmol) Qty (mL)

456237 Human CYP3A7 + reductase + b5 0.5 0.5

456221 Human CYP4A11 + reductase 0.5 0.5

456272 Human CYP4F2 + reductase + b5 0.5 0.5

456273 Human CYP4F3A + reductase + b5 0.25 0.5

456274 Human CYP4F3B + reductase + b5 0.5 0.5

456275 Human CYP4F12 + reductase + b5 0.5 0.5

456260 Human CYP19 (aromatase) + reductase 0.5 0.5

Human UGT Enzymes Protein Concentration Cat. No. Description (mg/mL) Qty (mL)

456400 UGT control microsomes 5 0.5

456411 Human UGT 1A1 5 0.5

456413 Human UGT 1A3 5 0.5

456414 Human UGT 1A4 5 0.5

456416 Human UGT 1A6 5 0.5

456407 Human UGT 1A7 5 0.5

456418 Human UGT 1A8 5 0.5

456419 Human UGT 1A9 5 0.5

456410 Human UGT 1A10 5 0.5

456424 Human UGT 2B4 5 0.5

456427 Human UGT 2B7 5 0.5

453323 Human UGT 2B10 5 0.5

456435 Human UGT 2B15 5 0.5

456437 Human UGT 2B17 5 0.5 UGT = UDP-glucuronosyl transferases

Other Human Metabolic Enzymes Protein Concentration Cat. No. Description (mg/mL) Qty (mL)

453320 Human CES1b 5 0.5

453321 Human CES1c 5 0.5

453322 Human CES2 5 0.5

456241 Human FMO1 5 0.5

456233 Human FMO3 5 0.5

456245 Human FMO5 5 0.5

456280 Monoamine Oxidase (MAO) Control 5 0.5

456283 Human Monoamine Oxidase A (MAO-A) 5 0.5

456284 Human Monoamine Oxidase B (MAO-B) 5 0.5

456199 Insect cell Cytosol (for use with all NAT Corning® Supersomes™ 2.5 0.5 enzymes)

456281 Human NAT1 Cytosol 2.5 0.5

456282 Human NAT2 Cytosol 2.5 0.5 FMO = Flavin-containing monooxygenase, NAT = N-acetyltransferases.

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Rat P450 Enzymes Cat. No. Description P450 Content (nmol) Qty (mL)

456511 Rat CYP1A1 + reductase 1.0 nmol 0.5

456503 Rat CYP1A2 + reductase 0.5 nmol 0.5

456519 Rat CYP2A1 + reductase + b5 0.5 nmol 0.5

456505 Rat CYP2A2 + reductase + b5 0.5 nmol 0.5

456510 Rat CYP2B1 + reductase + b5 0.5 nmol 0.5

456536 Rat CYP2C6 + reductase + b5 0.5 nmol 0.5

456531 Rat CYP2C11 + reductase + b5 0.5 nmol 0.5

456532 Rat CYP2C12 + reductase + b5 0.5 nmol 0.5

456533 Rat CYP2C13 + reductase + b5 0.5 nmol 0.5

456517 Rat CYP2D1 + reductase 0.5 nmol 0.5

456513 Rat CYP2D2 + reductase 0.5 nmol 0.5

456521 Rat CYP2E1 + reductase + b5 0.5 nmol 0.5

456501 Rat CYP3A1 + reductase + b5 0.5 nmol 0.5

456502 Rat CYP3A2 + reductase + b5 0.5 nmol 0.5

Controls, Cofactors, and Buffers

Enzyme Controls

Analysis of cytochrome P450 isoform-specific metabolism requires use of the appropriate control preparation in order to eliminate the possibility of metabolism by enzymes native to the cell lines. Corning Life Sciences prepares control microsomes and cytosols using procedures identical to those used to prepare other microsomal products.

For P450 enzymes, control microsomes are available from both Sf9 and High Five (Hi5 or BTI-TN-5B1-4) insect cell preparations. All insect cell control microsomes are prepared from insect cells infected with wild-type baculovirus. Control preparations are also available for UGT, MAO, NAT, and CES Corning® Supersomes™ enzymes products.

Normalization of Protein Concentration

Differences in total protein concentration can affect the free concentration of substrate and hence enzyme kinetics. The available substrate concentration may be significantly lower than initially assumed for those substrates which have a large potential to bind nonspecifically to protein (J. Pharmacol. Exp. Ther. 283:46 [1997]; Drug Metab. Dispos. 25:1359 [1997]). Total protein concentra-tion can be controlled and normalized in each incubation by the addition of control microsomes.

NADPH Regenerating System

NADPH is a necessary cofactor in many xenobiotic metabolism reactions. NADPH is required for the measurement of oxidase activity catalyzed by P450s, FMOs, NADPH-P450 OR, and many other oxidase enzymes. A common source of NADPH in an oxidase enzyme assay is an NADPH regenerating system which generates NADPH in situ using an enzymatic reaction. For example, glucose-6-phosphate dehydrogenase (G6PDH) will convert NADP+ to NADPH in the presence of the substrate glucose- 6-phosphate (Glc-6-PO4).

The Corning Gentest™ NADPH regenerating system consists of two reagents, Solution A (NADP+ and Glc-6-PO4) and Solution B (G6PDH). Each reagent is sold separately. Combined, these two reagents form a NADPH regenerating system that can be used for all NADPH requiring oxidase assays (cDNA-expressed enzymes and liver fractions). At least 200 to 400 enzyme assays can be performed using one vial each of Solution A and B. The total number of assays that can be performed is dependent on a researcher’s experimental design.

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11 For more specific information on claims, visit the Certificates page at www.corning.com/lifesciences.

Corning® Supersomes™ Enzymes Controls Protein Concentration Cat. No. Description (mg/mL) Qty (mL)

456200 Insect cell control for Corning Supersomes enzymes 5 1.5 baculovirus-insect cell-expressed (BTI-TN-5B1-4 cells)

456201 Insect cell control for Corning Supersomes enzymes 5 0.5 baculovirus-insect cell-expressed (BTI-TN-5B1-4 cells)

456199 Insect cell cytosol control 2.5 0.5

456400 Human UGT Insect Control for Corning Supersomes enzymes 5 0.5

456280 MAO Insect Control for Corning Supersomes enzymes 5 0.5

456244 Human P450 reductase and b5 control for baculovirus 5 0.5 expressed (BTI-TN-5B1-4 cells)

Cofactors Cat. No. Description Qty (mL)

451220 NADPH Regenerating system – Solution A (NADP+ and Glc-6-PO4) 5

451200 NADPH Regenerating system – Solution B (G6PDH) 1

451300 UGT Reaction mix – Solution A 2

451320 UGT Reaction mix – Solution B 5

Buffers451201 Phosphate buffer (pH 7.4) 500

CHEMICAL SUBSTRATES, METABOLITE STANDARDS, AND INHIBITORS

Corning® Gentest™ chemicals are high quality products and are validated in ADME applications with Corning Supersomes™ enzymes, tissue fractions, and primary hepatocytes.

Stable Isotope Standards for use with Mass SpectrometryCat. No. Description CAS# CYP/UGT Application Qty (mg)

451006 4-Hydroxydiclofenac-[13C6] 64118-84-9 Internal metabolite standard CYP2C9 1

451009 6β-Hydroxytestosterone-[D7] 62-99-7 Internal metabolite standard CYP3A4 1

Fluorescent-labeled SubstrateCat. No. Description CAS# CYP/MFC/BFC/BQ Application Qty (mg)

451730 7-Benzyloxy-4-(trifluoromethyl)- coumarin (BFC) N/A Fluorescent CYP3A4 substrate 5

Unlabeled InhibitorCat. No. Description CAS# CYP Application Qty (mg)

451795 (S)-(+)-N-3-Benzylnirvanol N/A Competitive inhibitor CYP2C19 5

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TISSU E FRACTIONS

Tissue fractions from human and animal livers represent an important tool in preclinical metabolism studies for predicting the toxicity and pharmacokinetic properties of a drug compound. Liver micro-somes from humans and animal species play an important role in evaluating drug compounds for metabolic stability, reactive metabolites, drug-drug interactions, reaction phenotyping, and metabolite identification.

For years, Corning has been a trusted provider of a wide range of high quality tissue fractions, including liver and intestinal micro somes, as well as ancillary products (e.g., cofactors, chemical substrates, metabolites, and inhibitors) necessary to perform metabolism-based assays.

Corning Gentest microsomes, cytosol, and S9 subcellular fractions provide a convenient, cost-effective source of native enzymes responsible for phase I and phase II metabolism of drugs. These enzymes include cytochrome P450 enzymes (CYP), UDP-glucuronosyl transferases (UGT), and flavin-containing monooxygenase (FMO). As part of Corning Life Sciences’ on-going commitment to bringing innovative tools to life scientists and emerging areas of ADME/Tox research, Corning added a large donor pool of human liver microsomes (HLMs), the Corning UltraPool™ HLM 150, to the Corning portfolio of human liver microsomes. This large donor pool better represents the average patient population and known CYP polymorphisms, enabling consistent experimental results in multi-year programs, and offering a time savings by reducing the time required qualifying new lots of HLMs.

Corning Gentest allelic variant HLM panels are genotyped single donors designed to help address the growing concerns over drug safety for all patients including outlier population with polymorphorphic gene (CYPs, UGTs, etc.). Genetic polymorphisms exist for many drugs as most P450s have been shown to possess mutant alleles. Polymorphisms may also explain some idiosyncratic reactions. We have prepared panels where the 1% of the population has a genetic polymorphism with a CYP or UGT defect. Genotype allelic variant panels are available for CYP2C8, 2C9, 2C19, 2D6, 3A5, and UGT1A1.

Many steps are taken during the manufacture of all Corning Gentest tissue fraction products to reduce lot-to-lot variability and to ensure reproducibility. Complete assay results and donor information are provided on the product insert. Contact [email protected] to obtain up-to-date single donor information.

Note: All human tissues are prepared from donors who tested negative serologically for HIV-1, HIV-2, HTLV-1, HTLV-2, HBV, HCV, and syphilis. All tissues are subsequently tested for the same pathogens by PCR.

Overview of the manufacturing workflow

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13 For more specific information on claims, visit the Certificates page at www.corning.com/lifesciences.

Human Liver Microsome Tissue Fraction Products

Corning® Gentest™ Human Mixed Pooled Microsomes, Cytosol, and S9 Protein Concentration Cat. No. Description (mg/mL) Qty/Pk

452117 Mixed gender Corning UltraPool 150-donor HLM 20 0.5 mL (equal mix of male and female donors)

452118 Mixed gender Corning UltraPool 150-donor HLM 20 80 vials (80 vials of 452117 packaged in an easy-count box)

452116 Mixed gender Corning UltraPool 150-donor S9 20 1.0 mL

452115 Mixed gender Corning UltraPool 150-donor Cytosol 20 1.0 mL

452161 Mixed gender HLM mixed pooled (approx. 20 donors) 20 0.5 mL

452155 Mixed HLMs packaged in an easy-count box 20 80 vials (80 vials of 452161) (approx. 20 donors)

452961 Mixed gender pooled 20-donor S9 20 1 mL

Corning Gentest Human Pooled Specialty Products Cat. No. Description (mg/mL) Qty/Pk

452172 Pooled male HLM 20 0.5 mL

452183 Pooled female HLM 20 0.5 mL

452210 Mixed gender pooled intestinal microsomes 10 0.2 mL

Corning Gentest Human Individual Liver Microsomes Panel Protein Concentration Cat. No. Description (mg/mL) Qty/Pk

452138 P450 single donor HLM panel 20 0.5 mL High/low P450 single donor HLM panelThe most current list of donors can be found at www.corning.com/lifesciences/admetox.

Corning Gentest Individual Allelic Variant Donor Panels Protein Concentration Cat. No. Description (mg/mL) Qty/Pk

452142 CYP2C9(*2*2), (*2*3), and (*3*3) 20 0.5 mL

452144 CYP2C8(*3*3) 20 0.5 mL

452135 CYP3A5(*1*1) high expresser 20 0.5 mL

452137 CYP3A5(*3*3) wild-type low expresser 20 0.5 mL

452132 UGT1A1(*28*28) low expresser 20 0.5 mL

452133 UGT1A1(*1*28) moderate expresser 20 0.5 mL

452134 UGT1A1(*1*1) wild-type high expresser 20 0.5 mL‡Poor Metabolizer. Note: Orders must include donor lot number as well as catalog number. Each lot number corresponds with a specific donor. To view an up-to-date listing of donors with donor demographics, donor history, and characterization data, visit www.corning.com/lifesciences/admetox.

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Animal Liver Tissue Fraction ProductsCorning® Gentest™ Animal Pooled Liver Microsomes Rat Liver Microsomes

Cat. No. Description Protein Concentration (mg/mL) Qty (mL)

452501 Sprague-Dawley, male 20 0.5 mL

452502 Sprague-Dawley, female 20 0.5 mL

452511 Wistar Han, male 20 0.5 mL

Mouse Liver Microsomes 452220 B6C3F1, male 20 0.5 mL

452701 CD-1, male 20 0.5 mL

452702 CD-1, female 20 0.5 mL

Dog Liver Microsomes 452601 Beagle, male 20 0.5 mL

452602 Beagle, female 20 0.5 mL

Monkey Liver Microsomes 452413 Cynomolgus, male 20 0.5 mL

Mini-Pig Liver Microsomes 452322 Gottigen, male 20 0.5 mL

Rabbit Liver Microsomes 452201 New Zealand white, male 20 0.5 mLHazard Warning: Monkey tissue fractions are prepared from freshly frozen tissues. These materials are tested and found negative for Herpes B and SIV. It is recommended this material be considered a potential biohazard.

Corning Gentest Animal Pooled Liver S9Rat Liver S9 Cat. No. Description Protein Concentration (mg/mL) Qty (mL)

452591 Sprague-Dawley, male 20 1.0

Mouse Liver S9 452791 CD-1, male 20 1.0

Dog Liver S9 452693 Beagle, male 20 1.0

Monkey Liver S9 452494 Cynomolgus, male 20 1.0

Corning Gentest Animal Liver Cytosol Rat Liver CytosolCat. No. Description Protein Concentration (mg/mL) Qty (mL)

452581 (male) Sprague-Dawley, male 20 1.0

Monkey Liver Cytosol452461 (male) Cynomolgus, male 20 1.0 Hazard Warning: Monkey tissue fractions are prepared from freshly frozen tissues. These materials are tested and found negative for Herpes B and SIV. It is recommended this material be considered a potential biohazard.

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15 For more specific information on claims, visit the Certificates page at www.corning.com/lifesciences.

CORN I NG® GENTEST™ H UMAN CRYOH EPATOCYTES

Primary human hepatocytes are the “Gold Standard” for studying the metabolic fate of drugs and other foreign compounds, as they contain the full complement of drug metabolism enzymes and cofactors, transporter proteins, and nuclear receptor pathways for enzyme induction. These cells are also valuable tools for studying in vitro liver toxicity and liver disease modeling. Typical assays using primary hepatocytes include, but are not limited to metabolic stability, metabolite identification, hepatic uptake and efflux transport, drug-drug interaction studies such as CYP induction and toxicity studies.

Primary human hepatocytes are prepared from donor livers and are usually cryopreserved to provide the convenience of being readily available, supporting long-term studies with large quantities of cells from the same donor, and allowing for studying population variability with multiple donors simultaneously.

Corning Gentest Plateable Primary Human Hepatocytes

Assays using primary human hepatocytes can be conducted in either a suspension culture or plated culture on rat tail Collagen I-coated tissue cultureware such as Corning BioCoat™ plates. Hepatocytes in suspension culture can typically survive up to 4 hours and are generally used for shorter term metabolic stability, metabolite identification, or transporter uptake assays. In contrast to suspension hepatocytes, hepatocytes in plated culture can maintain hepatic morphology and function longer (up to 1-2 weeks), and are especially useful for assays requiring long-term culture such as CYP induction, metabolic stability for low turn-over compounds, and hepatic uptake and biliary efflux transporter activity study. Hepatocytes are typically cultured for several days in a Corning Matrigel® matrix/Collagen “Sandwich” culture to allow formation of bile canaliculi networks which are useful to study hepatic efflux transporter.

◗◗ Pre-screened and characterized for drug metabolism, CYP induction, and drug transport. Some lots may be suitable for multiple applications.

◗◗ These characterizations provide researchers with the data necessary to select lots which are well-suited to their research needs.

◗◗ Large selection of Corning tissue cultureware with extracellular matrix coatings are available for various applications using plateable primary human hepatocytes

For activities and donor demographic information, please contact [email protected].

Plateable Primary Human HepatocytesCat. No. Description Size Qty/Pk

454541 Corning Gentest plateable transporter-qualified human ≥5 million cells 1.5 mL cryohepatocytes

454543 Corning Gentest plateable metabolism-qualified human ≥5 million cells 1.5 mL cryohepatocytes

454551 Corning Gentest inducible-qualified human cryohepatocytes* ≥5 million cells 1.5 mL *Contact us about P450 induction study contract services at 888.334.5229 x2246 or 781.935.5115 x2246.

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Corning technologies to build a 3D PHH spheroid model. The bright field image and Haemotoxylin and Eosin (H&E) staining of a day 8 PHH spheroid are shown.

Spheroid-qualified PHHs and Corning Spheroid Microplates

3D PHH Spheroid

H&E Staining of Day 8 PHH Spheroid (1,000 cells/spheroid)

Corning® 3D Spheroid-qualified Primary Human Hepatocytes

3D liver spheroid culture has been shown to maintain the viability and functions of PHHs for several weeks (Bell, et al. 2016 and Lauschke, et al. 2016). Drug-induced liver injury (DILI) is a leading cause of drug development failures and post-marketing withdrawals. 3D PHH spheroids have been shown to significantly improve the sensitivity (2- to 3-fold) of in vitro hepatotoxicity assay in comparison to 2D PHH monolayer culture or spheroid cultures of hepatic cell lines such as HepaRG or stem cell-derived hepatocytes (Proctor, et al. 2017 and Bell, et al. 2017).

To support the increasing interest in applying the 3D liver spheroid model in drug discovery and development studies, we now offer 3D spheroid-qualified primary human hepatocytes using Corning spheroid microplates.

◗◗ Optimized spheroid culture procedures

◗◗ PHH spheroid formation in 6 to 7 days; stable morphology, viability, and hepatic functions in long-term culture

◗◗ Increased sensitivity in 3D hepatotoxicity assays

◗◗ Capable of co-culture with other liver cell types (e.g., Kupffer cells)

◗◗ Corning spheroid microplates available to support long-term 3D liver spheroid culture

Corning 3D Spheroid-qualified Primary Human Hepatocytes (PHHs)Cat. No. Description Qty

454552 Spheroid-qualified primary human hepatocytes ≥2 million cells/vial

Corning Spheroid Microplates Cat. No. Description Sterile Qty/Pk Qty/Cs

4515 96-well, black/clear round bottom, with lid, Yes 1 5 Ultra-Low Attachment surface

4520 96-well, black/clear round bottom, with lid, Yes 10 50 Ultra-Low Attachment surface

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17 For more specific information on claims, visit the Certificates page at www.corning.com/lifesciences.

Complementary Products for Hepatocyte Culture

Cat. No. Description Qty

355056 Corning® hepatocyte culture media kit 500 mL 500 mL plus EGF supplement. Use for serum-free medium to maintain hepatocyte cultures

in vitro; commonly used to culture plated human cryopreserved hepatocytes on Corning BioCoat™ rat tail Collagen I multiwell plates and flasks.

Other Related Products for Hepatocyte Culture

◗◗ Corning BioCoat Poly-D-Lysine cultureware

◗◗ Corning BioCoat Matrigel® matrix cultureware

◗◗ Corning BioCoat rat tail Collagen I cultureware

◗◗ Corning Matrigel basement membrane matrix

For more information on products for hepatocyte culture, visit www.corning.com/lifesciences.

CUSTOM PRODUCTS

In addition to the products listed in this guide, Corning has more than 20 years of experience offering custom special preparations from a wide range of species and tissues. Custom products include, but are not limited to, hepatocytes, tissue fractions, and recombinant enzymes. Our custom product team handles the complete process, including tissue ordering, preparation, concentration, packaging, characterization, and delivery. For additional information, please contact [email protected] or consult your Corning Drug Discovery Sales Specialist.

Important Ordering Information

HepatoLink® is the Corning Life Sciences immediate response system providing researchers with instant notification when Corning Gentest hepatocyte products are available. For your convenience, select a preferred contact method—email, phone, and/or SMS text alerts. Upon registration, you will be sent donor characterization data when a new lot becomes available. You can register online at www.corning.com/lifesciences/hepatolink. Place your order directly through Corning's online system. If you have any questions regarding Corning's program or your participation, please contact us at 978.442.2200 or email [email protected].

All Corning Gentest cryohepatocyte orders must be lot specific. Each lot number corresponds with a specific donor and must be included with your order. An up-to-date listing of Corning Gentest human cryohepatocyte donors with donor demo graphics, donor history, and characterization data is maintained at www.corning.com/lifesciences/admetox.

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Corning® GentestSM Contract Research Services have been serving customers for more than 20 years, supporting drug discovery and development programs, from secondary screens to post-marketing commitment. Our Study Directors are highly skilled scientists with an in-depth knowledge of enzyme induction, transporter interactions, metabolism, and toxicity. This expertise enables Corning Life Sciences Study Directors to partner with you to develop and deliver a broad range of in vitro ADME/Tox studies customized to meet your discovery and development project needs. We ensure the highest level of quality and adhere to current regulatory requirements and applicable regulatory agency guidance documents.

Utilizing state-of-the art materials, techniques, and equipment, Corning Life Sciences is ideally suited to assist you in screening for viable drug candidates during drug discovery or to prepare regulatory agency submission-quality reports for your drug development compounds. Let our team of experts take you to the next level with studies designed to predict drug-drug interactions and human pharmaco kinetics using the innovative Corning Gentest™ products, cell models, and methodologies.

Permeability and Transport Studies

ABC Transporters

A leader since 1998 in providing drug-transporter products and services, Corning offers diverse options with a comprehensive panel of ATP binding cassette (ABC) efflux transporters expressed in our transfected cell lines, vesicles, and membranes. From screening assays to comprehensive drug-drug interaction assessment studies, we can provide solutions to your efflux transporter assay needs. Corning’s bidirectional transport assays using Caco-2 and the Corning Gentest MDR1-LLC-PK1 cell lines comply with regulatory agency recommended approaches to determine test article apparent permeability (Papp) and assess P-glycoprotein (P-gp) mediated transport and inhibition. Screening and comprehensive interaction studies are also available for efflux transporters BCRP, BSEP, and MRPs, as recommended by regulatory agencies.

SLC Transporters

Using our solute carrier (SLC) over-expressing Corning TransportoCells™ product line, we conduct screening and step-wise approach drug-drug interaction assays to assess whether your test article is a substrate and/or inhibitor of uptake transporters in alignment with the latest FDA, EMA, and ITC recommendations for development of investigational drugs. Uptake assays can be performed with OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, MATE2-K, and additional transporters.

Metabolic Stability and Intrinsic Clearance

Corning provides rapid in vitro metabolic stability and intrinsic clearance testing using several different enzyme sources. Most often, this test utilizes hepatocytes or liver microsomes. Corning’s metabolic stability testing using hepatocytes features carefully selected, single-freeze donor pools with results provided for human and preclinical species to maintain data consistency from assay to assay. The use of Corning UltraPool™ HLM 150 microsomes ensures minimal inter-assay variability.

Enzyme Inhibition Studies

As the in vitro ADME market leader in cytochrome P450 (CYP) products and services, Corning provides CYP inhibition services with high quality data analysis. Assays are conducted using industry leading Corning UltraPool HLM 150 pooled human liver microsomes, drug probe substrates, and validated LC/MS/MS analysis methods using stable-labeled isotope internal standards. Capabilities include direct and time-dependent inhibition. Multiple endpoints are possible, including IC50, IC50 shift (dilution and non-dilution methodology), as well as Ki and kinact. Corning also provides a comprehensive suite of UGT inhibition assays that includes UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B4, 2B7, 2B15, and 2B17.

Contract Research Services

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19 For more specific information on claims, visit the Certificates page at www.corning.com/lifesciences.

Enzyme Induction Studies

Since 2002, Corning has been providing regulatory agency-driven cytochrome P450 (CYP) induction services using cryopreserved isolated human hepatocytes. The use of pre-qualified Corning® Gentest™ inducible cryopreserved hepatocytes ensures a predictable response and accelerated data availability. Testing options include enzyme activity and mRNA endpoints for CYP1A2, CYP2B6, CYP3A4, CYP2C8, CYP2C9, CYP2C19, UGTs, transporters, and more. Follow-up the conventional 3 donor, 3 CYP assays with relative induction scoring (RIS correlation method) in our panel of specially qualified human hepatocyte donors. Also available are rapid screening assays to determine induction of cytochrome P450 enzymes CYP1A2, CYP2B6, and CYP3A4. Standard screening assay determines induction of mRNA, and options include cytotoxicity and enzyme activity. Ask about our customized assays that can closely align with your in-house methods.

Reaction Phenotyping Studies

Reaction phenotyping studies help identify enzyme-mediated pathways of elimination for a compound — key information that affects population variability in metabolism and the risk of it becoming a victim drug in a drug-drug interaction event. Assays are performed using Corning Supersomes™ enzymes, human liver microsomes, chemical inhibitors, and/or immunoinhibitory antibodies. We can identify metabolic pathways catalyzed by multiple enzymes including CYPs, FMOs, UGTs, CES, SULT, and AO enzymes, to help identify the enzymology of metabolic pathways.

Custom Studies

Corning has expertise in adapting clients’ protocols to facilitate comparison with in-house databases of results. Customizations can include the choice of enzyme source, extracellular matrix, treatment media, positive control-inducing chemical/concentration, and delivery solvent, as well as many other client requirements. In addition, over many years we have built several assays to meet our customers' unique and diverse drug metabolism and drug transporter needs, and have provided hundreds of drug-metabolism in vitro ADME needs.

For more information on Corning GentestSM Contract Research Services, contact Corning Life Sciences at 888.334.5229 x2546, 781.938.2546, e-mail [email protected], or contact your local Corning Drug Discovery Sales Specialist or Account Manager.

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Visit www.corning.com/lifesciences for additional product and technical information.20

3380 . . . . . . . . . . . . . . . . . . . . . . . 63392 . . . . . . . . . . . . . . . . . . . . . . . 63401 . . . . . . . . . . . . . . . . . . . . . . . 63412 . . . . . . . . . . . . . . . . . . . . . . . 63413 . . . . . . . . . . . . . . . . . . . . . . . 63450 . . . . . . . . . . . . . . . . . . . . . . . 63460 . . . . . . . . . . . . . . . . . . . . . . . 63470 . . . . . . . . . . . . . . . . . . . . . . . 64515 . . . . . . . . . . . . . . . . . . . . . . 164520 . . . . . . . . . . . . . . . . . . . . . . 16351130. . . . . . . . . . . . . . . . . . . . . 6351131. . . . . . . . . . . . . . . . . . . . . 6351180. . . . . . . . . . . . . . . . . . . . . 5351181. . . . . . . . . . . . . . . . . . . . . 5351186. . . . . . . . . . . . . . . . . . . . . 5353015. . . . . . . . . . . . . . . . . . . . . 5353047. . . . . . . . . . . . . . . . . . . . . 5353090. . . . . . . . . . . . . . . . . . . . . 6353095. . . . . . . . . . . . . . . . . . . . . 6353102. . . . . . . . . . . . . . . . . . . . . 7353103. . . . . . . . . . . . . . . . . . . . . 7353104. . . . . . . . . . . . . . . . . . . . . 7353180. . . . . . . . . . . . . . . . . . . . . 6353493. . . . . . . . . . . . . . . . . . . . . 7353494. . . . . . . . . . . . . . . . . . . . . 7353495. . . . . . . . . . . . . . . . . . . . . 7353502. . . . . . . . . . . . . . . . . . . . . 7353503. . . . . . . . . . . . . . . . . . . . . 7353504. . . . . . . . . . . . . . . . . . . . . 7353924. . . . . . . . . . . . . . . . . . . . . 6353925. . . . . . . . . . . . . . . . . . . . . 6353935. . . . . . . . . . . . . . . . . . . . . 5353938. . . . . . . . . . . . . . . . . . . . . 6354801. . . . . . . . . . . . . . . . . . . . . 5354802. . . . . . . . . . . . . . . . . . . . . 5354803. . . . . . . . . . . . . . . . . . . . . 5354804. . . . . . . . . . . . . . . . . . . . . 5354841 . . . . . . . . . . . . . . . . . . . . 3354842 . . . . . . . . . . . . . . . . . . . . 3354843 . . . . . . . . . . . . . . . . . . . . 3354851 . . . . . . . . . . . . . . . . . . . . 3354852 . . . . . . . . . . . . . . . . . . . . 3354853 . . . . . . . . . . . . . . . . . . . . 3354854 . . . . . . . . . . . . . . . . . . . . 3354855 . . . . . . . . . . . . . . . . . . . . 3354856 . . . . . . . . . . . . . . . . . . . . 3354857 . . . . . . . . . . . . . . . . . . . . 3354858 . . . . . . . . . . . . . . . . . . . . 3354859 . . . . . . . . . . . . . . . . . . . . 3

354860 . . . . . . . . . . . . . . . . . . . . 3354861 . . . . . . . . . . . . . . . . . . . . 3354862 . . . . . . . . . . . . . . . . . . . . 3354863 . . . . . . . . . . . . . . . . . . . . 3354864 . . . . . . . . . . . . . . . . . . . . 3354866 . . . . . . . . . . . . . . . . . . . . 3354867 . . . . . . . . . . . . . . . . . . . . 3354868 . . . . . . . . . . . . . . . . . . . . 3354878 . . . . . . . . . . . . . . . . . . . . 3354879 . . . . . . . . . . . . . . . . . . . . 3355056. . . . . . . . . . . . . . . . . . . . 17355467. . . . . . . . . . . . . . . . . . . . . 7451006. . . . . . . . . . . . . . . . . . . . 11451009. . . . . . . . . . . . . . . . . . . . 11451010. . . . . . . . . . . . . . . . . . . . 11451041. . . . . . . . . . . . . . . . . . . . . 5451200. . . . . . . . . . . . . . . . . . . . 11451201. . . . . . . . . . . . . . . . . . . . 11451220. . . . . . . . . . . . . . . . . . . . 11451300. . . . . . . . . . . . . . . . . . . . 11451320. . . . . . . . . . . . . . . . . . . . 11451730. . . . . . . . . . . . . . . . . . . . 11451795. . . . . . . . . . . . . . . . . . . . 11452115. . . . . . . . . . . . . . . . . . . . 13452116. . . . . . . . . . . . . . . . . . . . 13452117. . . . . . . . . . . . . . . . . . . . 13452118. . . . . . . . . . . . . . . . . . . . 13452132. . . . . . . . . . . . . . . . . . . . 13452133. . . . . . . . . . . . . . . . . . . . 13452134. . . . . . . . . . . . . . . . . . . . 13452135. . . . . . . . . . . . . . . . . . . . 13452137. . . . . . . . . . . . . . . . . . . . 13452138. . . . . . . . . . . . . . . . . . . . 13452142. . . . . . . . . . . . . . . . . . . . 13452144. . . . . . . . . . . . . . . . . . . . 13452155. . . . . . . . . . . . . . . . . . . . 13452161. . . . . . . . . . . . . . . . . . . . 13452172. . . . . . . . . . . . . . . . . . . . 13452183. . . . . . . . . . . . . . . . . . . . 13452201. . . . . . . . . . . . . . . . . . . . 14452210. . . . . . . . . . . . . . . . . . . . 13452220. . . . . . . . . . . . . . . . . . . . 14452322. . . . . . . . . . . . . . . . . . . . 14452413. . . . . . . . . . . . . . . . . . . . 14452461. . . . . . . . . . . . . . . . . . . . 14452494. . . . . . . . . . . . . . . . . . . . 14452501. . . . . . . . . . . . . . . . . . . . 14452502. . . . . . . . . . . . . . . . . . . . 14452511. . . . . . . . . . . . . . . . . . . . 14

452581. . . . . . . . . . . . . . . . . . . . 14452591. . . . . . . . . . . . . . . . . . . . 14452601. . . . . . . . . . . . . . . . . . . . 14452602. . . . . . . . . . . . . . . . . . . . 14452693. . . . . . . . . . . . . . . . . . . . 14452701. . . . . . . . . . . . . . . . . . . . 14452702. . . . . . . . . . . . . . . . . . . . 14452791. . . . . . . . . . . . . . . . . . . . 14452961. . . . . . . . . . . . . . . . . . . . 13453320. . . . . . . . . . . . . . . . . . . . . 9453321. . . . . . . . . . . . . . . . . . . . . 9453322. . . . . . . . . . . . . . . . . . . . . 9453323. . . . . . . . . . . . . . . . . . . . . 9453800. . . . . . . . . . . . . . . . . . . . . 4453801. . . . . . . . . . . . . . . . . . . . . 4453802. . . . . . . . . . . . . . . . . . . . . 4453803. . . . . . . . . . . . . . . . . . . . . 4453804. . . . . . . . . . . . . . . . . . . . . 4453805. . . . . . . . . . . . . . . . . . . . . 4453806. . . . . . . . . . . . . . . . . . . . . 4454541. . . . . . . . . . . . . . . . . . 4, 15454543. . . . . . . . . . . . . . . . . . . . 15454551. . . . . . . . . . . . . . . . . . . . 15454552. . . . . . . . . . . . . . . . . . . . 16456199. . . . . . . . . . . . . . . . . . 9, 11456200. . . . . . . . . . . . . . . . . . . . 11456201. . . . . . . . . . . . . . . . . . . . 11456202. . . . . . . . . . . . . . . . . . . . . 8456203. . . . . . . . . . . . . . . . . . . . . 8456204. . . . . . . . . . . . . . . . . . . . . 8456206. . . . . . . . . . . . . . . . . . . . . 8456207. . . . . . . . . . . . . . . . . . . . . 8456209. . . . . . . . . . . . . . . . . . . . . 8456210. . . . . . . . . . . . . . . . . . . . . 8456211. . . . . . . . . . . . . . . . . . . . . 8456212. . . . . . . . . . . . . . . . . . . . . 8456217. . . . . . . . . . . . . . . . . . . . . 8456218. . . . . . . . . . . . . . . . . . . . . 8456219. . . . . . . . . . . . . . . . . . . . . 8456220. . . . . . . . . . . . . . . . . . . . . 8456221. . . . . . . . . . . . . . . . . . . . . 9456222. . . . . . . . . . . . . . . . . . . . . 8456233. . . . . . . . . . . . . . . . . . . . . 9456235. . . . . . . . . . . . . . . . . . . . . 8456237. . . . . . . . . . . . . . . . . . . . . 9456241. . . . . . . . . . . . . . . . . . . . . 9456242. . . . . . . . . . . . . . . . . . . . . 8456244. . . . . . . . . . . . . . . . . . . . 11456245. . . . . . . . . . . . . . . . . . . . . 9

456252. . . . . . . . . . . . . . . . . . . . . 8456254. . . . . . . . . . . . . . . . . . . . . 8456255. . . . . . . . . . . . . . . . . . . . . 8456256. . . . . . . . . . . . . . . . . . . . . 8456258. . . . . . . . . . . . . . . . . . . . . 8456259. . . . . . . . . . . . . . . . . . . . . 8456260. . . . . . . . . . . . . . . . . . . . . 9456264. . . . . . . . . . . . . . . . . . . . . 8456272. . . . . . . . . . . . . . . . . . . . . 9456273. . . . . . . . . . . . . . . . . . . . . 9456274. . . . . . . . . . . . . . . . . . . . . 9456275. . . . . . . . . . . . . . . . . . . . . 9456280. . . . . . . . . . . . . . . . . . 9, 11456281. . . . . . . . . . . . . . . . . . . . . 9456282. . . . . . . . . . . . . . . . . . . . . 9456283. . . . . . . . . . . . . . . . . . . . . 9456284. . . . . . . . . . . . . . . . . . . . . 9456400. . . . . . . . . . . . . . . . . . 9, 11456407. . . . . . . . . . . . . . . . . . . . . 9456410. . . . . . . . . . . . . . . . . . . . . 9456411. . . . . . . . . . . . . . . . . . . . . 9456413. . . . . . . . . . . . . . . . . . . . . 9456414. . . . . . . . . . . . . . . . . . . . . 9456416. . . . . . . . . . . . . . . . . . . . . 9456418. . . . . . . . . . . . . . . . . . . . . 9456419. . . . . . . . . . . . . . . . . . . . . 9456424. . . . . . . . . . . . . . . . . . . . . 9456427. . . . . . . . . . . . . . . . . . . . . 9456435. . . . . . . . . . . . . . . . . . . . . 9456437. . . . . . . . . . . . . . . . . . . . . 9456501. . . . . . . . . . . . . . . . . . . . 10456502. . . . . . . . . . . . . . . . . . . . 10456503. . . . . . . . . . . . . . . . . . . . 10456505. . . . . . . . . . . . . . . . . . . . 10456510. . . . . . . . . . . . . . . . . . . . 10456511. . . . . . . . . . . . . . . . . . . . 10456513. . . . . . . . . . . . . . . . . . . . 10456517. . . . . . . . . . . . . . . . . . . . 10456519. . . . . . . . . . . . . . . . . . . . 10456521. . . . . . . . . . . . . . . . . . . . 10456531. . . . . . . . . . . . . . . . . . . . 10456532. . . . . . . . . . . . . . . . . . . . 10456533. . . . . . . . . . . . . . . . . . . . 10456536. . . . . . . . . . . . . . . . . . . . 10459010. . . . . . . . . . . . . . . . . . . . . 4459011. . . . . . . . . . . . . . . . . . . . . 4

Catalog Number Index

Cat. No. Page No. Cat. No. Page No. Cat. No. Page No. Cat. No. Page No.

Page 23: ADME/Tox Product Selection Guide · 459011 BSEP vesicle assay kit N/A – Up to 200 assays Corning Gentest™ Transporter Kits Corning transporter membrane and vesicle kits provide
Page 24: ADME/Tox Product Selection Guide · 459011 BSEP vesicle assay kit N/A – Up to 200 assays Corning Gentest™ Transporter Kits Corning transporter membrane and vesicle kits provide

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For more specific information on claims, visit the Certificates page at www.corning.com/lifesciences.

Warranty/Disclaimer: Unless otherwise specified, all products are for research use only. Not intended for use in diagnostic or therapeutic procedures. Not for use in humans. Corning Life Sciences makes no claims regarding the performance of these products for clinical or diagnostic applications.

Use of Genetically Modified Microorganisms (GMMO)Information for European Customers: Corning® TransportoCells™ products are genetically modified microorganisms as described in Corning Life Sciences technical literature. As a condition of sale, use of these products must be in accordance with all applicable local guidelines on the contained use of genetically modified microorganisms, including the Directive 2009/41/EC of the European Parliament and of the Council.

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For additional product or technical information, visit www.corning.com/lifesciences or call 800.492.1110. Outside the United States, call +1.978.442.2200 or contact your local Corning sales office.

Corning IncorporatedLife Sciences836 North St. Building 300, Suite 3401 Tewksbury, MA 01876t 800.492.1110 t 978.442.2200 f 978.442.2476www.corning.com/lifesciences

A S I A / P A C I F I C

Australia/New Zealandt 61 427286832Chinat 86 21 3338 4338f 86 21 3338 4300India t 91 124 4604000f 91 124 4604099

Japant 81 3-3586 1996 f 81 3-3586 1291Koreat 82 2-796-9500 f 82 2-796-9300Singaporet 65 6572-9740 f 65 6735-2913Taiwant 886 2-2716-0338 f 886 2-2516-7500

E U R O P [email protected] 0800 916 882f 0800 918 636Germanyt 0800 101 1153 f 0800 101 2427The Netherlands t 020 655 79 28f 020 659 76 73United Kingdomt 0800 376 8660f 0800 279 1117

All Other European Countriest +31 (0) 206 59 60 51 f +31 (0) 206 59 76 73

L A T I N A M E R I C [email protected]

Brasilt 55 (11) 3089-7400Mexicot (52-81) 8158-8400