XL888

Stage

IND Submitted

Indications

Various Tumor Types

Principal Targets

XL888 is an orally available small molecule inhibitor of HSP90, which is a chaperone protein that promotes the activity and stability of a range of key regulatory proteins, including kinases. The activity of HSP90 is particularly prominent in tumor cells where it promotes the activity of proteins controlling growth 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.

Preclinical Data

In preclinical studies, XL888 inhibits the proliferation of a broad panel of human tumor cell lines and induces marked degradation of HSP90 client proteins XL888 is highly active in multiple human tumor xenograft models. Pharmacokinetic studies in models demonstrate that XL888 is preferentially retained in tumors relative to plasma and liver. The activity profile of XL888 is highly supportive of its clinical development for the treatment of cancers driven by HSP90 client proteins.