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Drug Design Chapter 2: Drug Discovery, Design, and Development (Part 1)
Descrição
Principles of Drug Design Chemistry 5332
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chemistry
drug design
drug discovery
drug development
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gibbons530
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Resumo de Recurso
Drug Design Chapter 2: Drug Discovery, Design, and Development (Part 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. 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. Lead Modifications
(continued in part 2 of Chapter 2)
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