Pharmacology 4620A Lecture Notes - Lecture 1: Drug Discovery, Lead Compound, Transcription Activator-Like Effector Nuclease
15 Nov 2018
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Lecture 1: Molecular and Structural Basis of Drug Action
Overview of Drug Discovery Process
● Historical Source of Drugs
● Target based rational drug discovery
● Examples of HTS screening assays
● Identification of lead compounds
● Phases of clinical trials
Drugs from naturally occurring substances
● PHYTOCHEMICALS
○ Alkaloids
○ Non-Alkaloidal Plant Products
○ Plant Product Analogues
○ E.g. Opioids (poppy plant), Quinine
● BIOCHEMICALS
○ Hormones
○ Vitamines
○ Blood and blood products
○ E.g. Insulin, Growth Hormone
■ Naturally present in the body but can also be made exogenously
● DRUGS FROM MICROORGANISMS
○ Antibiotics
○ E.g. Penicillin, Streptomycin
Types of Drug Molecules
● Small Organic Molecules
○ MW < 500 Daltons
■ Kept small so that it is easily digestible and disturbed to its target in the
body
○ Usually administered oral
● Proteins
○ MW > 10,000 Daltons
○ Usually injectable
■ Can’t be admistiend orally because it will be digested
● Vaccines
● Engineered cells (“living drug”)
○ E.g. CAR-T cells
○ Take out and engineer the host’s T-cells to recognize cancer and reintroduced to
the host
● RNA based therapeutics (siRNA)
○ Suppress translation
● Gene Therapy (CRISPR/Cas9, TALENS)
○ Now: used for editing the the CAR-T cells after it is removed from the host
Document Summary
Lecture 1: molecular and structural basis of drug action. Naturally present in the body but can also be made exogenously. Kept small so that it is easily digestible and disturbed to its target in the body. Can"t be admistiend orally because it will be digested. Take out and engineer the host"s t-cells to recognize cancer and reintroduced to the host. Now: used for editing the the car-t cells after it is removed from the host. Finding a target that is important in a certain disease and can be modified by a chemical compound to treat that disease. Identify a lead compound that binds to the target of interest. Start to improve the compound (change the chemical structure) Change it so that it can be administered it orally, etc. Administer the drug to a small group healthy volunteers to test safety. Administer the drug to healthy volunteers to test long term toxicology.
