doi: 10.1016/j.bmcl.2012.07.052.
Epub 2012 Jul 21.
Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90
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- PMID: 22877636
- DOI: 10.1016/j.bmcl.2012.07.052
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Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90
Bioorg Med Chem Lett.
.
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.
Copyright © 2012 Elsevier Ltd. All rights reserved.
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