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Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90.

Publication ,  Journal Article
Fadden, P; Huang, KH; Veal, JM; Steed, PM; Barabasz, AF; Foley, B; Hu, M; Partridge, JM; Rice, J; Scott, A; Dubois, LG; Freed, TA; Barta, TE ...
Published in: Chem Biol
July 30, 2010

A chemoproteomics-based drug discovery strategy is presented that utilizes a highly parallel screening platform, encompassing more than 1000 targets, with a focused chemical library prior to target selection. This chemoproteomics-based process enables a data-driven selection of both the biological target and chemical hit after the screen is complete. The methodology has been exemplified for the purine binding proteome (proteins utilizing ATP, NAD, FAD). Screening of an 8000 member library yielded over 1500 unique protein-ligand interactions, which included novel hits for the oncology target Hsp90. The approach, which also provides broad target selectivity information, was used to drive the identification of a potent and orally active Hsp90 inhibitor, SNX-5422, which is currently in phase 1 clinical studies.

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Published In

Chem Biol

DOI

EISSN

1879-1301

Publication Date

July 30, 2010

Volume

17

Issue

7

Start / End Page

686 / 694

Location

United States

Related Subject Headings

  • Substrate Specificity
  • Small Molecule Libraries
  • Proteomics
  • Organic Chemistry
  • Molecular Conformation
  • Models, Molecular
  • Mice
  • Humans
  • HSP90 Heat-Shock Proteins
  • Female
 

Citation

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ICMJE
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Fadden, P., Huang, K. H., Veal, J. M., Steed, P. M., Barabasz, A. F., Foley, B., … Hall, S. E. (2010). Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90. Chem Biol, 17(7), 686–694. https://doi.org/10.1016/j.chembiol.2010.04.015
Fadden, Patrick, Kenneth H. Huang, James M. Veal, Paul M. Steed, Amy F. Barabasz, Briana Foley, Mei Hu, et al. “Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90.Chem Biol 17, no. 7 (July 30, 2010): 686–94. https://doi.org/10.1016/j.chembiol.2010.04.015.
Fadden P, Huang KH, Veal JM, Steed PM, Barabasz AF, Foley B, et al. Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90. Chem Biol. 2010 Jul 30;17(7):686–94.
Fadden, Patrick, et al. “Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90.Chem Biol, vol. 17, no. 7, July 2010, pp. 686–94. Pubmed, doi:10.1016/j.chembiol.2010.04.015.
Fadden P, Huang KH, Veal JM, Steed PM, Barabasz AF, Foley B, Hu M, Partridge JM, Rice J, Scott A, Dubois LG, Freed TA, Silinski MAR, Barta TE, Hughes PF, Ommen A, Ma W, Smith ED, Spangenberg AW, Eaves J, Hanson GJ, Hinkley L, Jenks M, Lewis M, Otto J, Pronk GJ, Verleysen K, Haystead TA, Hall SE. Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90. Chem Biol. 2010 Jul 30;17(7):686–694.

Published In

Chem Biol

DOI

EISSN

1879-1301

Publication Date

July 30, 2010

Volume

17

Issue

7

Start / End Page

686 / 694

Location

United States

Related Subject Headings

  • Substrate Specificity
  • Small Molecule Libraries
  • Proteomics
  • Organic Chemistry
  • Molecular Conformation
  • Models, Molecular
  • Mice
  • Humans
  • HSP90 Heat-Shock Proteins
  • Female