Rational drug design

1. CONCEPT OF RATIONAL
DRUG DESIGN
BY VIKAS GUPTA
M.PHARM [PHARMACOLOGY]

2. CONTENTS
• Introduction
• Types of drug design
• Structure based drug design
• Ligand based drug design
• Concept of rational drug design
• Types of rational drug designing method
• Examples of the drug that are synthesized by using rational drug design method
• Drawbacks of drug design

3. INTRODUCTION
• Drug design is the inventive process of finding new
medications based on the knowledge of the biological
target.
• Modeling techniques for prediction of binding affinity
are reasonably successful.
• However there are many other properties such as
bioavailability, metabolic half-life, lack of side effects,
etc. that first must be optimized before a ligand can
become a safe and efficacious drug

4. TYPES OF DRUG DESIGN
Rational drug design can be broadly divided into two categories:
DRUG DESIGN
STRUCTURE BASED
DRUG DESIGN
LIGAND BASED DRUG
DESIGN

5. STRUCTURE BASED DRUG DESIGN
• Structure based drug design (direct drug design) relies on knowledge of the three
dimensional structure of biological target obtained through methods such as X-ray
crystallography or NMR Spectroscopy.
• Don’t know ligand.
• Know structure of ligand.
• 3D structure of receptor.

6. STEPS INVOLVED IN STRUCTURE BASED DRUG DESIGN

7. LIGAND BASED DRUG DESIGN
• Ligand-based drug design (or indirect drug design) relies on knowledge of
other molecules that bind to the biological target of interest.
• These other molecules may be used to derive a pharmacophore model which
defines the minimum necessary structural characteristics a molecule must
possess in order to bind to the target.

9. STEPS INVOLVED IN LIGAND BASED DRUG DESIGN

11. CONCEPT OF RATIONAL DRUG DESIGN
• Rational drug design refers to the development of medications based on the
study of the structures and functions of target molecules. That is to say, the
role of rational drug design is to use a methodological approach to coming up
with a new drug, as opposed to blindly hoping some stroke of luck helps
design a new drug, or instead of randomly testing hundreds of drug molecules
in hopes that one of them binds to a receptor and exerts a therapeutic effect.

12. BASIC REQUIREMENT
• Typically a drug target is a key molecule involved in a particular metabolic or signaling
pathway that is specific to a disease condition or pathology, or to the infectivity or survival of
a microbial pathogen. Some approaches attempt to inhibit the functioning of the pathway in
the diseased state by causing a key molecule to stop functioning. Drugs may be designed that
bind to the active region and inhibit this key molecule.
• Drug interactions with off-target molecules may lead to undesirable side effect. Sequence
homology is often used to identify such risks.

14. TYPES OF RATIONAL DRUG DESIGNING METHOD
• 3D structure of biological target [Receptor based drug design]
• Structure of known active small molecules [Pharmacophore based drug
design]
• Computer Assisted drug design [CAAD]
• Molecular graphics
• Pattern recognition

15. EXAMPLES OF THE DRUG THAT ARE SYNTHESIZED BY USING
RATIONAL DRUG DESIGN METHOD
• Antidotes
• Antimetabolites
• Enzyme inhibitor

16. DRAWBACK OF RATIONAL DRUG DESIGN
• Time consuming
• Costly
• Limited understanding of drug receptors
• Labour intensive
• Low hit rate generated