What distinguishes target validation from hit identification?

Why

Start with a therapeutic hypothesis: changing target activity in a specific direction should alter disease biology without unacceptable harm. Use genetics, disease tissue expression, perturbation experiments and independent models to test it. Hit identification is a different task: screening finds chemical or biological matter that produces a desired assay signal.

A compound that inhibits a purified kinase is a preliminary hit, not proof that this kinase is causally important to disease. Conversely, a genetically compelling disease target may have no suitable small-molecule hits yet. An effective program combines the two paths by using orthogonal chemistry, cellular target-engagement assays and phenotype rescue experiments.

Drug exposure, tissue selectivity and safety remain major risks even after a target and an initial hit look promising. Avoid using the word validated for evidence that only shows correlation or one readout.