The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors

  • Bioorg Med Chem Lett. 2005 Jul 15;15(14):3338-43. doi: 10.1016/j.bmcl.2005.05.046.
Kwai-Ming J Cheung  1 ,  Thomas P Matthews ,  Karen James ,  Martin G Rowlands ,  Katherine J Boxall ,  Swee Y Sharp ,  Alison Maloney ,  S Mark Roe ,  Chrisostomos Prodromou ,  Laurence H Pearl ,  G Wynne Aherne ,  Edward McDonald ,  Paul Workman
Affiliations
  • 1. Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Cancer Research UK and Haddow Laboratories, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
PMID: 15955698 DOI: 10.1016/j.bmcl.2005.05.046
Abstract

High-throughput screening identified the 3,4-diarylpyrazole CCT018159 as a novel and potent (7.1 microM) inhibitor of HSP90 ATPase activity. Here, we describe the synthesis of CCT018159 and a number of close analogues together with data on their biochemical properties. Some initial structure-activity relationships are discussed, as well as the crystal structure of CCT018159 bound to HSP90.