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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • July 30, 2010

Published In

Volume / Issue

  • 17 / 7

Start / End Page

  • 686 - 694

PubMed ID

  • 20659681

Electronic International Standard Serial Number (EISSN)

  • 1879-1301

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2010.04.015


  • eng

Conference Location

  • United States