6 drug design - rose-hulman institute of technologybrandt/chem430/6_drug_design.pdf · find or...
TRANSCRIPT
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Introduction to Drug Design
(Sex, drugs, and rock and roll . . . well,
drugs, anyway.)
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Drugs
Definition: articles intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease in man or
other animals, intended to affect the structure or any
function of the body of man or other animals.
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Biologically Active Species
Elements/Ions
Natural Products
Organic Compounds
Peptides
Proteins
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Types of Drugs
Hormone Agonists
Hormone Antagonists
Enzyme Modulators
Ion Channel Inhibitors
Antibodies
Enzymes
Vaccines
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Designing Drugs
1. Find a possible route for intervention
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Designing Drugs
2. Find or Design a compound
a. Brute force
b. Rational drug design
Pharmacophore
SAR
QSAR
Structure-based
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Designing Drugs
2. Find or Design a compound
c. Lead compound
d. Modified compounds
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Testing
1. Pre-clinical
2. Phase 0
3. Phase I
4. Phase II
5. Phase III
6. Phase IV
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Confounding Factors
Genetic variation
Life-style effects
Gender effects
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Circannual Variation
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Effect of Circannual Variations
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Technical Issues
Pharmacodynamics
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Technical Issues
Pharmacokinetics: ADME/Tox
Absorption
Distribution
Metabolism
Excretion
Toxicology
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Technical Issues
Lipinski’s Rule of Five:
Log P ! 5
Hydrogen bond donor ! 5
Hydrogen bond acceptor ! 10
Molecular weight ! 500
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Absorption
Oral
Inhaled
Injected
Intravenous
Sub-cutaneous
Intramuscular
Intraperitoneal
Transdermal
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Distribution
Mechanism
Topical
Blood
Blood-brain barrier
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Metabolism
How
Results
Location
Rate
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Excretion
Route
Mechanism
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Toxicology
Side-effects
IC50
ED50
TD50
LD50
Therapeutic index: TD50/ED50
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Production
“Particle Physics”
Consistency of dose
Stability
Size
Elegance