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Cell DOI:10.1016/j.cell.2015.05.023

Advancing Biological Understanding and Therapeutics Discovery with Small-Molecule Probes.

Publication TypeJournal Article
Year of Publication2015
AuthorsSchreiber, SL, Kotz, JD, Li, M, Aubé, J, Austin, CP, Reed, JC, Rosen, H, E White, L, Sklar, LA, Lindsley, CW, Alexander, BR, Bittker, JA, Clemons, PA, de Souza, A, Foley, MA, Palmer, M, Shamji, AF, Wawer, MJ, McManus, O, Wu, M, Zou, B, Yu, H, Golden, JE, Schoenen, FJ, Simeonov, A, Jadhav, A, Jackson, MR, Pinkerton, AB, D Y Chung, T, Griffin, PR, Cravatt, BF, Hodder, PS, Roush, WR, Roberts, E, Chung, D-H, Jonsson, CB, Noah, JW, Severson, WE, Ananthan, S, Edwards, B, Oprea, TI, P Conn, J, Hopkins, CR, Wood, MR, Stauffer, SR, Emmitte, KA
Corporate AuthorsNIH Molecular Libraries Project Team
JournalCell
Volume161
Issue6
Pages1252-65
Date Published2015 Jun 04
ISSN1097-4172
KeywordsAnimals, Drug Discovery, Enzyme Inhibitors, High-Throughput Screening Assays, Humans, National Institutes of Health (U.S.), Small Molecule Libraries, United States
Abstract

Small-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 NIH 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.

DOI10.1016/j.cell.2015.05.023
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/26046436?dopt=Abstract

Alternate JournalCell
PubMed ID26046436
PubMed Central IDPMC4564295
Grant ListU54 HG005033 / HG / NHGRI NIH HHS / United States
U54 MH084691 / MH / NIMH NIH HHS / United States
U54 MH084512 / MH / NIMH NIH HHS / United States
U54 MH084659-01 / MH / NIMH NIH HHS / United States
U54 MH084659 / MH / NIMH NIH HHS / United States
1 U54 HG005034-01 / HG / NHGRI NIH HHS / United States
1 U54 HG005031-01 / HG / NHGRI NIH HHS / United States
U54 HG005032 / HG / NHGRI NIH HHS / United States
U54 MH084690-01 / MH / NIMH NIH HHS / United States
U54 MH084690 / MH / NIMH NIH HHS / United States
1 U54 HG005032-01 / HG / NHGRI NIH HHS / United States
U54 MH084681-01 / MH / NIMH NIH HHS / United States
U54 MH084691-01 / MH / NIMH NIH HHS / United States
U54 HG005031 / HG / NHGRI NIH HHS / United States
R13 NS084681 / NS / NINDS NIH HHS / United States
U54 MH084512-01 / MH / NIMH NIH HHS / United States
U54 HG005034 / HG / NHGRI NIH HHS / United States
1 U54 HG005033-01 / HG / NHGRI NIH HHS / United States