Jackson

Question 1

Lead Optimization

Answer 1

• Pharmacokinetics / dose linearity -drug levels
• Protein Binding
• Metabolite ID
• Metabolic stability -species
• Genotoxicity
• Selectivity screening
• Drug-drug interactions -HLM
• Blood brain barrier
• CV in vivo testing

Question 2

Safety: AMES Test

Answer 2

• Ability of a compound to cause mutations in DNA

- Potential for a compound to be carcinogenic

Question 3

Safety: HERG Channel Interactions

Answer 3

• Human Ether-a-go-go Related Gene
• Voltage gated K ion channel in heart
• Early indication of potential cardiovascular effects

Question 4

Lead Optimization Parameters: ADME

Answer 4

ADME: Absorption, Distribution, Metabolism, Excretion

• Oral bioavailability (solubility/permeability)
• Plasma half-life
• Plasma protein binding
• Cytochrome P450 enzymes
• P-glycoprotein (pgp) efflux