Drug Design Chapter 2: Drug Discovery, Design, and Development (Part 1)

Drug Design Chapter 2: Drug Discovery, Design, and Development (Part 1)

1. 1. Drug Discovery

   • Before 19th century: drugs were mainly herbs and potions
     • Mid 19th century: scientists attempted to isolate and purify active components
   • A. Statistics
     • Average time to market: 12-15 years
     • Average cost: $600-800 billion
     • Cost to get on market today: $1.2 billion
   • B. Choosing a Disease
     • How are target disases chosen? Logical... Practical...
   • C. Clinical Trials
     • Before clinical trials...
       • 1) in vitro and in vivo testing on cell cultures or transgenic mice
         • 2) test on lab animals for several months
     • Four Phases of Clinical Trials
       • Phase 1: healthy volunteers
         • Phase 2: small group of volunteers
           • Phase 3: larger group of patients
             • Phase 4: never-ending
             • Drug can be licensed, marketed, and prescribed

2. 2. Finding a Lead Compound

   • Prototype Compound
     • Drug Candidate
       • Clinical Drug
   • A) No Lead Compound (Serendipity)
     • 1) Penicillins
       • bacteria culture accidentally contaminated with a mold
     • 2) Mustard Gas
       • led to first chemotherapy drug, mustine
     • 3) Cisplatin
       • inhibited bacterial cell division when electric field was applied
   • B) Lead Discovery
     • bioassay: test system
     • in vitro tests: cells, tissues, enzymes, receptors
     • in vivo tests: animals
   • C) Random Screening
     • all compounds tested in bioassay, regardless of structure
       • synthetic chemicals
       • natural products
       • "War on Cancer" allowed new compounds to be screened for free
   • D) Nonrandom Screening
     • targeted screening
     • budget concerns
     • looking for weak activity or similar structures
   • E) Metabolites
     • in vivo drug degradation products
       • often in active compound
   • F) Clinical Observations
     • observe side effects of drugs in clinical trials
       • Example: Dramamine
   • G) Rational Approaches
     • "computer-aided design"
     • 1) Identify cause of the disease
       • 2) Design molecules which correct an imbalance or stop cell growth

3. 3. Lead Modifications

   • (continued in part 2 of Chapter 2)