1149383-72-1Relevant articles and documents
Discovery of XL888: A novel tropane-derived small molecule inhibitor of HSP90
Bussenius, Joerg,Blazey, Charles M.,Aay, Naing,Anand, Neel K.,Arcalas, Arlyn,Baik, Taegon,Bowles, Owen J.,Buhr, Chris A.,Costanzo, Simona,Curtis, Jeffrey K.,Defina, Steven C.,Dubenko, Larisa,Heuer, Timothy S.,Huang, Ping,Jaeger, Christopher,Joshi, Anagha,Kennedy, Abigail R.,Kim, Angie I.,Lara, Katherine,Lee, Jae,Li, Jonathan,Lougheed, Julie C.,Ma, Sunghoon,Malek, Shiva,Manalo, Jean-Claire L.,Martini, Jean-Francois,McGrath, Garth,Nicoll, Monique,Nuss, John M.,Pack, Michael,Peto, Csaba J.,Tsang, Tsze H.,Wang, Longcheng,Womble, Scott W.,Yakes, Michael,Zhang, Wentao,Rice, Kenneth D.
, p. 5396 - 5404 (2012/09/22)
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.
