Lecture 23 - Drug Discovery and Development Flashcards
Functional classification of Protein Theraputics
Group I: Enzymes and regulatory proteins - Ia
Replaces a protein that is deficient or abnormal (ex. insulin, growth hormone, factor VIII, factor IX)
Functional classification of Protein Theraputics
Group I: Enzymes and Regulatory Proteins - Ib
Augmenting a existing pathway (ex. EPO, G-CSF, IL-11, FSH, HCG, interferons)
Functional classification of Protein Theraputics
Group I: Enzymes and regulatory proteins - Ic
Providing a novel function or activity (ex. botulinum toxin, streptokinase)
Functional classification of Protein Theraputics
Group II: Targeted proteins - IIa
Interfering with a molecule or organism (ex. Avastin to treat colon cancer, anti-TNF antibodies, anti-CD20, anti-CD3)
Functional classification of Protein Theraputics
Group II: Targeted Proteins - IIb
Delivers other compounds or proteins (ex. Ontak: anti-IL2 antibody, cancer drug delivery)
Functional classification of Protein Theraputics
Group III: Protein vaccines - IIIa
Protecting against a deleterious foreign agent (e. HPV vaccine, Prevnar 13)
Functional classification of Protein Theraputics
Group III: Protein vaccines - IIIb
Treating an autoimmune disease (ex. Anti-Rh IgG)
Functional classification of Protein Theraputics
Group III - Protein vaccines - IIIc
Treats cancer (under development)
Functional classification of Protein Theraputics
Group IV: Protein diagnostics
Secretin (pancreatic exocrine dysfunction, gastinoma), HIV antigens, Hep C antigens, GHRH (abnormal growth hormone release), ACTH (adrenal insufficiency), glucagon (aid to slow GI motility)
What is a biomarker?
A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease
What is drug discovery?
Spans the period from the identification of a potential therapeutic target to the selection of molecules to be tested in humans (everything before preclinical trials)
What is drug development?
The period from the preclinical studies tat support clinical trials to te approval of the drug by regulatory authorities (Usually 3 phases of clinical trials)
What are the advantages to a compound-centered approach to drug discovery?
- Bioactive or natural products already have certain biological activity
- May be easier to isolate compound from natural source than synthesize
- May be feasible to use the natural compound as a starting point to form a semisynthetic product
Microorganisms, plants, animals, synthetic chemicals, natural ligands
What are the disadvantages to a compound-centered approach to drug discovery?
- It takes significant effort to isolate and synthesize a natural product
- In vivo mechanism of action is often unknown for many atural products at first
Examples of drugs made using a compound-centered approach
Cyclosporine, Digoxin, Morphine, Penicillin G, Streptokinase
What is the target-centered approach to drug discovery?
Uses a known molecule in the disease pathway as a target (ex. receptors, enzymes, transporters, kinases, and ion channels)
What are the advantages of Target-centered drug discovery?
- If the validated target has been associated wit a disease process, a hit has a relatively high likelyhood of useful pharmacologic activity
- It may be easier to devise assays capable of isolating the effect of potential hits on the known target
