Advancing biological understanding and therapeutics discovery with small-molecule probes

Stuart L. Schreiber; Joanne D. Kotz; Min Li; Jeffrey Aubé; Christopher P. Austin; John C. Reed; Hugh Rosen; E. Lucile White; Larry A. Sklar; Craig W. Lindsley; Benjamin R. Alexander; Joshua A. Bittker; Paul A. Clemons; Andrea De Souza; Michael A. Foley; Michelle Palmer; Alykhan F. Shamji; Mathias J. Wawer; Owen McManus; Meng Wu; Beiyan Zou; Haibo Yu; Jennifer E. Golden; Frank J. Schoenen; Anton Simeonov; Ajit Jadhav; Michael R. Jackson; Anthony B. Pinkerton; Thomas D.Y. Chung; Patrick R. Griffin; Benjamin F. Cravatt; Peter S. Hodder; William R. Roush; Edward Roberts; Dong Hoon Chung; Colleen B. Jonsson; James W. Noah; William E. Severson; Subramaniam Ananthan; Bruce Edwards; Tudor I. Oprea; P. Jeffrey Conn; Corey R. Hopkins; Michael R. Wood; Shaun R. Stauffer; Kyle A. Emmitte

doi:10.1016/j.cell.2015.05.023

Advancing biological understanding and therapeutics discovery with small-molecule probes

Stuart L. Schreiber, Joanne D. Kotz, Min Li, Jeffrey Aubé, Christopher P. Austin, John C. Reed, Hugh Rosen, E. Lucile White, Larry A. Sklar, Craig W. Lindsley, Benjamin R. Alexander, Joshua A. Bittker, Paul A. Clemons, Andrea De Souza, Michael A. Foley, Michelle Palmer, Alykhan F. Shamji, Mathias J. Wawer, Owen McManus, Meng WuBeiyan Zou, Haibo Yu, Jennifer E. Golden, Frank J. Schoenen, Anton Simeonov, Ajit Jadhav, Michael R. Jackson, Anthony B. Pinkerton, Thomas D.Y. Chung, Patrick R. Griffin, Benjamin F. Cravatt, Peter S. Hodder, William R. Roush, Edward Roberts, Dong Hoon Chung, Colleen B. Jonsson, James W. Noah, William E. Severson, Subramaniam Ananthan, Bruce Edwards, Tudor I. Oprea, P. Jeffrey Conn, Corey R. Hopkins, Michael R. Wood, Shaun R. Stauffer, Kyle A. Emmitte

School of Medicine

Research output: Contribution to journal › Review article › peer-review

95 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1252-1265
Number of pages	14
Journal	Cell
Volume	161
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2015.05.023
State	Published - 2015

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2015.05.023

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Schreiber, S. L., Kotz, J. D., Li, M., Aubé, J., Austin, C. P., Reed, J. C., Rosen, H., White, E. L., Sklar, L. A., Lindsley, C. W., Alexander, B. R., Bittker, J. A., Clemons, P. A., De Souza, A., Foley, M. A., Palmer, M., Shamji, A. F., Wawer, M. J., McManus, O., ... Emmitte, K. A. (2015). Advancing biological understanding and therapeutics discovery with small-molecule probes. Cell, 161(6), 1252-1265. https://doi.org/10.1016/j.cell.2015.05.023

Schreiber, SL, Kotz, JD, Li, M, Aubé, J, Austin, CP, Reed, JC, Rosen, H, White, EL, 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, Chung, TDY, Griffin, PR, Cravatt, BF, Hodder, PS, Roush, WR, Roberts, E, Chung, DH, Jonsson, CB, Noah, JW, Severson, WE, Ananthan, S, Edwards, B, Oprea, TI, Conn, PJ, Hopkins, CR, Wood, MR, Stauffer, SR & Emmitte, KA 2015, 'Advancing biological understanding and therapeutics discovery with small-molecule probes', Cell, vol. 161, no. 6, pp. 1252-1265. https://doi.org/10.1016/j.cell.2015.05.023

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title = "Advancing biological understanding and therapeutics discovery with small-molecule probes",

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.",

author = "Schreiber, {Stuart L.} and Kotz, {Joanne D.} and Min Li and Jeffrey Aub{\'e} and Austin, {Christopher P.} and Reed, {John C.} and Hugh Rosen and White, {E. Lucile} and Sklar, {Larry A.} and Lindsley, {Craig W.} and Alexander, {Benjamin R.} and Bittker, {Joshua A.} and Clemons, {Paul A.} and {De Souza}, Andrea and Foley, {Michael A.} and Michelle Palmer and Shamji, {Alykhan F.} and Wawer, {Mathias J.} and Owen McManus and Meng Wu and Beiyan Zou and Haibo Yu and Golden, {Jennifer E.} and Schoenen, {Frank J.} and Anton Simeonov and Ajit Jadhav and Jackson, {Michael R.} and Pinkerton, {Anthony B.} and Chung, {Thomas D.Y.} and Griffin, {Patrick R.} and Cravatt, {Benjamin F.} and Hodder, {Peter S.} and Roush, {William R.} and Edward Roberts and Chung, {Dong Hoon} and Jonsson, {Colleen B.} and Noah, {James W.} and Severson, {William E.} and Subramaniam Ananthan and Bruce Edwards and Oprea, {Tudor I.} and Conn, {P. Jeffrey} and Hopkins, {Corey R.} and Wood, {Michael R.} and Stauffer, {Shaun R.} and Emmitte, {Kyle A.}",

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year = "2015",

doi = "10.1016/j.cell.2015.05.023",

language = "English (US)",

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pages = "1252--1265",

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AU - Schreiber, Stuart L.

AU - Kotz, Joanne D.

AU - Li, Min

AU - Aubé, Jeffrey

AU - Austin, Christopher P.

AU - Reed, John C.

AU - Rosen, Hugh

AU - White, E. Lucile

AU - Sklar, Larry A.

AU - Lindsley, Craig W.

AU - Alexander, Benjamin R.

AU - Bittker, Joshua A.

AU - Clemons, Paul A.

AU - De Souza, Andrea

AU - Foley, Michael A.

AU - Palmer, Michelle

AU - Shamji, Alykhan F.

AU - Wawer, Mathias J.

AU - McManus, Owen

AU - Wu, Meng

AU - Zou, Beiyan

AU - Yu, Haibo

AU - Golden, Jennifer E.

AU - Schoenen, Frank J.

AU - Simeonov, Anton

AU - Jadhav, Ajit

AU - Jackson, Michael R.

AU - Pinkerton, Anthony B.

AU - Chung, Thomas D.Y.

AU - Griffin, Patrick R.

AU - Cravatt, Benjamin F.

AU - Hodder, Peter S.

AU - Roush, William R.

AU - Roberts, Edward

AU - Chung, Dong Hoon

AU - Jonsson, Colleen B.

AU - Noah, James W.

AU - Severson, William E.

AU - Ananthan, Subramaniam

AU - Edwards, Bruce

AU - Oprea, Tudor I.

AU - Conn, P. Jeffrey

AU - Hopkins, Corey R.

AU - Wood, Michael R.

AU - Stauffer, Shaun R.

AU - Emmitte, Kyle A.

PY - 2015

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AB - 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.

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SN - 0092-8674

VL - 161

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EP - 1265

JO - Cell

JF - Cell

IS - 6

ER -

Advancing biological understanding and therapeutics discovery with small-molecule probes

Abstract

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