(quantitative) structure-activity relationships (q)sar
DESCRIPTION
(Quantitative) Structure-Activity Relationships (Q)SAR. Why QSAR. Safety evaluation Alternative testing methods High throughput, efficiency Predictive value. What is QSAR. In silico toxicity testing “Machine learning” method Pattern recognition. Applications. - PowerPoint PPT PresentationTRANSCRIPT
(Quantitative) Structure-Activity Relationships
(Q)SAR
Why QSAR
• Safety evaluation
• Alternative testing methods
• High throughput, efficiency
• Predictive value
What is QSAR
• In silico toxicity testing
• “Machine learning” method
• Pattern recognition
Applications
• Drug discovery - mechanism based design
• Drug development - efficacy/toxicity
• Environmental toxicity - human and wildlife
• Environmental fate - accumulation, biodegradation, photodegradation, etc
Categories of chemicals
• Drugs: agonists, antagonists, inhibitors of specific molecules
• POPs• Endocrine disruptors• Carcinogens• Narcotics in aquatic environment• Pesticides• Neurotoxins
Mutagenicity
Other in vitro tests
Mutagenicity in vivo
Carcinogenicity
FDA Cancer Male Rat CommercialCDER Proprietary MRFDA Cancer Female RatCDER Proprietary FRFDA Cancer Male MouseCDER Proprietary MMFDA Cancer Female MouseCDER Proprietary FM
CPDB Rat TD50 mg/kg DK-EPACPDB Mouse TD50 mg/kgCPDB Liver Specific (Rat or Mouse)
To open the database, visit http://ecbqsar.jrc.it
Tamura 2003 OP pesticides and androgen receptor
Structure analogues of non-steroidal antiandrogens
Testosterone antagonism by methylparathion and ethylfenitrothion
Structure alignment of DHT and fenitrothion in receptor binding site
Androgen receptor conformation and
critical residues for ligand interaction