XL880

Status : investigational

Description

XL880 is an orally available small molecule compound designed to target multiple RTKs implicated in the development, progression and spread of cancer. It inhibits the activation of MET, RON, ERK and AKT, decreased proliferation and increased apoptosis.

Used

Investigated for use/treatment in gastric cancer, renal cell carcinoma, and solid tumors.

Mechanism Of Action

Activation of MET by mutation is the causative factor in an inherited kidney cancer syndrome, hereditary papilliary renal cell carcinaoma. Mutational activation of MET has also been found in sporadic kidney cancer, lung carcinomas and head and neck carcinomas. MET is a key driver of tumor cell growth, motility, invasion, metastasis and angiogenesis. XL880 has attractive pharmaceutical properties with high solubility and oral bioavailability and demonstrates nanomolar potency against its targets, VEGFR, MET, which translates to potent activity in cellular assays. In preclinical studies, XL880, deveopled as a balanced inhibitor of these receptor tyrosine kinases, potently inhibited both MET and VEGFR, including mutant activated forms of MET found in hereditary papillary renal carcinomas. The compound also demonstrated dose-dependent growth inhibition in tumor models of breast, colorectal, non-small cell lung cancer and glioblastoma and has been shown to cause substantial tumor regression in all models tested.

Chemical Classification

Calculated Property

kind Value Source

Target within organism

  • Hepatocyte growth factor : in Human
  • Vascular endothelial growth factor receptor 2 : in Human