XL888 is a potent small molecule inhibitor of HSP90 with IC50 of 24 nM, inhibits cell proliferation of multiple cancer cell types.
XL888 potently inhibited cell growth, induced apoptosis, and prevented the growth of vemurafenib-resistant melanoma cell lines in 3-dimensional cell culture, long-term colony formation assays, and human melanoma mouse xenografts.
XL888 treatment increased BIM expression, decreased Mcl-1 expression, and induced apoptosis.
XL888 is effective at reversing BRAF inhibitor resistance in melanoma, including that mediated through acquired NRAS mutations.
