XL888

XL888 is an orally available small molecule inhibitor of HSP90, a chaperone protein that promotes the activity and stability of a range of client proteins, including kinases, which play key regulatory roles in cells. The activity of HSP90 is particularly prominent in tumor cells, where it promotes the activity of proteins controlling proliferation and survival. XL888 is a potent and selective ATP-competitive inhibitor of HSP90, and binds to its target in a manner that is structurally distinct from other HSP90 inhibitors currently in the clinic.

XL888 is being evaluated in a phase 1 trial in patients with solid tumors.  This trial was initiated based on a substantial body of preclinical data demonstrating that XL888 induces marked degradation of HSP90 client proteins and inhibits the proliferation of a broad panel of human tumor cell lines that are dependent on client proteins. XL888 is highly active in multiple human tumor xenograft models and has a favorable pharmacokinetic profile. The preclinical activity profile of XL888 is highly supportive of its clinical development for the treatment of cancers that are driven by proteins regulated by HSP90.