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(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.
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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
Other in vitro tests
Mutagenicity in vivo
Carcinogenicity FDA Cancer Male Rat Commercial CDER Proprietary MR FDA Cancer Female Rat CDER Proprietary FR FDA Cancer Male Mouse CDER Proprietary MM FDA Cancer Female Mouse CDER Proprietary FM CPDB Rat TD50 mg/kg DK-EPA CPDB Mouse TD50 mg/kg CPDB Liver Specific (Rat or Mouse) To open the database, visit http://ecbqsar.jrc.it
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