Which term describes a method that starts from a receptor's natural ligand and modifies it to create analogues?

• A. A form of rational drug design using 3D structure.
• B. A high-throughput screening method.
• C. Analogues of natural ligands
• D. Target-centered design using a known target.

Answer: (C)

Starting from a receptor’s natural ligand and modifying it to create analogues is a ligand-based approach that uses the natural ligand as the starting point for exploration. By tweaking functional groups, stereochemistry, or other features of the endogenous molecule, researchers map structure–activity relationships to improve binding affinity, selectivity, and pharmacokinetic properties. This strategy centers on what is already known about the natural ligand's interaction with the receptor and builds analogues around that framework. It differs from structure-based rational design, which starts from the receptor’s 3D structure to design new binders; high-throughput screening, which searches large libraries without a known starting ligand; and target-centered design, which focuses on the target itself rather than modifying a ligand. Hence, the approach described is analogues of natural ligands.