1.
Bioorg Med Chem Lett
; 22(17): 5396-404, 2012 Sep 01.
Article
in English
| MEDLINE
| ID: mdl-22877636
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.