relevant to the mission of participating NIH Institutes with the intent to screen for small molecule compounds that show potential as probes for use in advancing knowledge about the known targets, identifying new targets, or as pre-therapeutic leads; 2) screen implementation high throughput target-focused approaches or moderate throughput phenotypic- and fragment-based approaches to identify initial screening hits; 3) hit validation, including implementation of secondary assays that are orthogonal to the primary assay, advanced cheminformatics analysis and initial medicinal chemistry inspection to prioritize the hit set, and follow-up assays to characterize mode and mechanism of action of the validated hits; 4) hit-to-lead optimization, including SAR to optimize target engagement, selectivity and to minimize chemical liabilities, ADME, PK and PD studies, and, if appropriate, in vivo modeling to test efficacy or biological effects.