Druggability

Druggability is a term used in drug discovery to describe a biological target (such as a protein) that is known or predicted to bind with high affinity to a drug. Importantly, binding of the drug to the target must result in a functional change that provides a therapeutic benefit to the patient. In other words, the target must be disease-modifying. The concept of druggability is most commonly applied to the ability of drug targets to bind small molecules—low molecular weight organic compounds. However, the term has also been extended to encompass biologic medical products, such as therapeutic monoclonal antibodies.

The term “druggable genome” was originally coined by Hopkins et al. to describe proteins with genetic sequences similar to those of known drug targets and capable of binding "rule of five"-compliant small molecules. Related concepts include “ligandability”, “bindability”, and “(chemical) tractability”.

Drug discovery involves a series of stages that progress from a biological hypothesis to an approved drug. The process typically begins with target identification. Candidate targets may be selected based on various experimental criteria, including disease linkage (e.g. mutations in the protein are known to cause disease), mechanistic rationale (e.g. the protein is part of a pathway implicated in disease), or evidence from genetic screens in model organisms. However, disease relevance alone is not sufficient for a protein to serve as a drug target, the target must also be druggable.