druggability

Druggability is a concept in pharmacology that describes the likelihood that a biological target can be modulated by a drug-like molecule to achieve a therapeutic effect. It reflects both the biology of the target and the practical feasibility of discovering compounds with sufficient potency, selectivity, safety, and suitable pharmacokinetic properties to influence disease processes.

Most commonly druggable targets are proteins such as enzymes (for example kinases), receptors including G protein–coupled receptors and ion channels, and transporters. Extracellular proteins and secreted factors can be addressed with biologics, while intracellular targets require small molecules or alternative modalities. Structural and biophysical features that influence druggability include the presence of binding pockets or allosteric sites, tractable interaction surfaces, and the ability to reach the target within cells or tissues.

Assessment of druggability involves several steps. Target validation uses genetic and pharmacological evidence to show that modulating the target affects disease-relevant pathways. Tractability assessment examines whether the target has a modifiable binding site, whether ligands can be developed with sufficient affinity and selectivity, and whether modulation is likely to produce a therapeutic effect without unacceptable toxicity. In silico predictions, structure-based drug design, fragment-based screening, and high-throughput screening are common methods to probe druggability. Early considerations of pharmacokinetics and safety (ADME/Tox) also influence whether a target is pursued.

Some targets are regarded as undruggable, such as certain transcription factors or protein–protein interfaces. Advances in modalities like allosteric modulators, targeted protein degradation (for example PROTACs), peptide and RNA-based approaches, and other technologies have broadened the range of targets considered druggable.