2. Academic Validation
  3. Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90

Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90

  • Bioorg Med Chem Lett. 2012 Sep 1;22(17):5396-404. doi: 10.1016/j.bmcl.2012.07.052.
Joerg Bussenius 1,  Charles M Blazey,  Naing Aay,  Neel K Anand,  Arlyn Arcalas,  TaeGon Baik,  Owen J Bowles,  Chris A Buhr,  Simona Costanzo,  Jeffrey K Curtis,  Steven C DeFina,  Larisa Dubenko,  Timothy S Heuer,  Ping Huang,  Christopher Jaeger,  Anagha Joshi,  Abigail R Kennedy,  Angie I Kim,  Katherine Lara,  Jae Lee,  Jonathan Li,  Julie C Lougheed,  Sunghoon Ma,  Shiva Malek,  Jean-Claire L Manalo,  Jean-Francois Martini,  Garth McGrath,  Monique Nicoll,  John M Nuss,  Michael Pack,  Csaba J Peto,  Tsze H Tsang,  Longcheng Wang,  Scott W Womble,  Michael Yakes,  Wentao Zhang,  Kenneth D Rice
Affiliations

Affiliation

  • 1 Exelixis, Inc., 220 East Grand Ave., South San Francisco, CA 94080, USA.
PMID: 22877636 DOI: 10.1016/j.bmcl.2012.07.052
Abstract

With structural guidance, tropane-derived HTS hits were modified to optimize for HSP90 inhibition and a desirable in vivo profile. Through an iterative SAR development process 12i (XL888) was discovered and shown to reduce HSP90 client protein content in PD studies. Furthermore, efficacy experiments performed in a NCI-N87 mouse xenograft model demonstrated tumor regression in some dosing regimens.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-13313
    99.39%, HSP Inhibitor
    HSP