drugtarget

A drug target is a molecule in the body whose activity can be modulated by a therapeutic agent to produce a beneficial effect. Most drug targets are biological macromolecules, such as proteins or nucleic acids. The most common targets are receptors, enzymes, transporters, and ion channels, though some therapies aim to modify gene expression or protein interactions at the level of nucleic acids or multi-protein complexes.

Target classes include G protein-coupled receptors (GPCRs), kinases and other enzymes, ion channels, transporters, transcription factors, and nuclear receptors. Drug targets are evaluated for their accessibility in diseased tissues, their role in disease pathways, and their potential to yield clinically meaningful effects when modulated with acceptable safety.

Identification and validation of targets involve integrating disease biology, genetics, and systems biology. Approaches include genetic association studies, transcriptomic and proteomic profiling, and phenotypic screens. Validation uses genetic knockdown or knockout models, selective chemical probes, and in vivo studies to demonstrate that target modulation produces the desired phenotype with manageable safety.

Drug discovery states that a target should be druggable, meaning it can be modulated by a small molecule or biologic with sufficient potency and selectivity. After target selection, researchers develop assays to measure engagement and effect, screen or design compounds, optimize pharmacokinetic and safety properties, and demonstrate target engagement in relevant models before advancing to clinical testing.

Challenges in targeting biology include pathway redundancy, compensatory mechanisms, tissue-specific expression, species differences, and potential off-target effects. Public databases such as DrugBank, ChEMBL, Therapeutic Target Database, and Pharos provide information on targets, ligands, and related pharmacology.