Schreiber, StuartKotz, Joanne D.Li, MinAubé, JeffreyAustin, Christopher P.Reed, John C.Rosen, HughWhite, E. LucileSklar, Larry A.Lindsley, Craig W.Alexander, Benjamin R.Bittker, Joshua A.Clemons, Paul A.de Souza, AndreaFoley, MPalmer, MichelleShamji, AlykhanWawer, Mathias J.McManus, OwenWu, MengZou, BeiyanYu, HaiboGolden, Jennifer E.Schoenen, Frank J.Simeonov, AntonJadhav, AjitJackson, Michael R.Pinkerton, Anthony B.Chung, Thomas D.Y.Griffin, Patrick R.Cravatt, Benjamin F.Hodder, Peter S.Roush, William R.Roberts, EdwardChung, Dong-HoonJonsson, Colleen B.Noah, James W.Severson, William E.Ananthan, SubramaniamEdwards, BruceOprea, Tudor I.Conn, P. JeffreyHopkins, Corey R.Wood, Michael R.Stauffer, Shaun R.Emmitte, Kyle A.Brady, Linda S.Driscoll, JamieLi, Ingrid Y.Loomis, Carson R.Margolis, Ronald N.Michelotti, EnriquePerry, Mary E.Pillai, AjayYao, Yong2017-07-182015Schreiber, Stuart L., Joanne D. Kotz, Min Li, Jeffrey Aubé, Christopher P. Austin, John C. Reed, Hugh Rosen, et al. 2015. “Advancing Biological Understanding and Therapeutics Discovery with Small-Molecule Probes.” Cell 161 (6) (June): 1252–1265. doi:10.1016/j.cell.2015.05.023.0092-8674http://nrs.harvard.edu/urn-3:HUL.InstRepos:33464154Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the U.S. National Institutes of Health launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines, but also highlight the need to innovate the science of therapeutic discovery.en-USJournal Article2017-05-1620152017-07-1810.1016/j.cell.2015.05.023