|
|||||
|
|
Discovery of XL888: A novel tropane-derived small molecule inhibitor of HSP90 |
|
| Authors: | Joerg Bussenius 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 |
| Institution: | Exelixis, Inc., 220 East Grand Ave., South San Francisco, CA 94080, USA. |
| 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. |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ | |