Drug Discovery and Development Process

Drug Discovery and Development

• Drug discovery and development involve converting a lead compound to a more suitable drug by maintaining or augmenting favorable characteristics and abolishing drawbacks.

Lead Optimization

• Lead optimization involves improving pharmacodynamic and pharmacokinetic properties of a drug.
• This includes improving activity, reducing side effects, and enhancing pharmacokinetic properties.

Pharmacodynamics and Pharmacokinetics

• Pharmacodynamics is the study of what a drug does to the body.
• Pharmacokinetics is the study of what the body does to a drug.
• Pharmacokinetic properties include absorption, distribution, metabolism, and excretion (ADME) of a drug.

Metabolism of Drugs

• The body treats drugs as foreign substances, or xenobiotics, and tries to remove them by excretion in the urine.
• The kidney is set up to allow polar substances to escape in the urine, so the body tries to chemically transform the drugs into more polar structures.
• Phase 1 Metabolism involves the conversion of nonpolar bonds to more polar bonds, catalyzed by the cytochrome P450 system.

Traditional Drug Discovery

• Traditional drug discovery has disadvantages, including being irrational, based on serendipity and intuition, and being time-consuming with low output.
• It often involves a "Me Too Approach" with no de novo design.

Rational Drug Design

• Rational Drug Design is a process based on designing a drug upon the structure of its protein target.
• It starts with a validated biological target and ends up with a drug that optimally interacts with the target and triggers the desired biological action.
• It involves designing small molecules that are complementary in shape and charge to the biomolecular target.

Computer-Aided Drug Design (CADD)

• CADD is used for three major purposes: virtual screening, designing novel compounds, and guiding the optimization of lead compounds.
• CADD helps to filter large compound libraries, design novel compounds, and optimize lead compounds for affinity, metabolism, and pharmacokinetics properties.

Lead Compound Development

• Once a lead has been discovered, it is important to understand precisely which structural features are responsible for its biological activity.
• This involves identifying the "pharmacophore" - the structural features directly responsible for activity.

Pharmacophore

• The pharmacophore is the precise section of the molecule that is responsible for biological activity.
• Identifying the pharmacophore enables the preparation of a more active molecule by eliminating "excessive" functionality, thus reducing toxicity and cost of production.