MO3 Drug Lead Discovery

Question 1

List the sources of drug leads

Answer 1

1. Natural sources/products (derived from plants and animals)
2. Screening of compounds ( potential drug candidates are identified from a large collection of chemical compounds (‘compound library’) to find ‘hits’- compounds that show desirable biological activity such as binding to a target protein).
3. Synthesis / Rational design (focused on creating new compounds or modifying existing ones based on a deep understanding of the biological target and the properties required for a successful drug. Not much is known about the protein target)
4. Direct (do know about the protein target)
   - From endogenous compounds (potential drug candidates are based on compounds naturally found within the body)
   - structure based drug design (relies on a detailed 3D structure of a biological target to guide the design of potential drugs candidates)
   - virtual screening (computational technique to identify drug candidates by virtually screening large libraries of compounds against a specific biological target. Uses computer simulations unlike traditional screening to predict how well a compound will bind to the target binding site).
5. Enhancing a side effect (unintended effect of a drug is intentionally amplified to create new drug and eliminate original effect of drug)
6. Serendipity (unexpected discovery while researching something else).
7. Drug Metabolism (bio transformation of a drug compound within the body involving chemical alteration of a drug by enzymes. Metabolism is assessed to help predict behaviour in the body).
8. Me Too drugs (analogues) (drugs that are sturcturally similar to an existing frug with minor modifications, developed to achieve the same therapeudic effect).

Question 2

Describe how salbutamol was developed

Answer 2

• From natural endogenous ligands. Adrenaline hits all adrenergic receptors (alpha and beta) but adding alkyl groups on N gave beta selectivity.

Question 3

How are drug leads identified and developed

Answer 3

• disease identified
• biological targets are identified that are involved in a disease process and when modulated (activated or inhibited) produce a therapeutic effect.
• Molecules are found which are ‘hits’ that interact with the target in a way that may lead to therapeutic effect.
• Hit compounds are modified to improve properties while reducing toxicity.
• Drug undergoes more detailed testing in lab and on animals to ashes safety, efficiency and toxicity in pre clinical trials
• clinical trials
• approval and circulation