altiratinib

Description: Altiratinib (also known as DCC-2701 and DP-5164) is an orally active, highly potent and selective multi-kinase inhibitor with IC50 values of 2.7, 8, 9.2, 9.3, 0.85, 4.6, 0.83 nM for MET, TIE2, VEGFR2, FLT3, Trk1, Trk2, and Trk3. It was designed based on the rationale of engineering a single therapeutic agent able to address multiple hallmarks of cancer. Specifically, altiratinib inhibits not only mechanisms of tumor initiation and progression, but also drug resistance mechanisms in the tumor and microenvironment through balanced inhibition of MET, TIE2 (TEK), and VEGFR2 (KDR) kinases. Altiratinib potently inhibits cellular proliferation in MET-amplified EBC-1 and MKN-45 cells, as well as TPM3-TRKA fusion KM-12 cells. Altiratinib exhibits properties amenable to oral administration and exhibits substantial blood-brain barrier penetration, an attribute of significance for eventual treatment of brain cancers and brain metastases.

References: Mol Cancer Ther. 2015 Sep; 14(9):2023-34.