Definition

An orally available selective inhibitor of the receptor tyrosine kinase c-ros oncogene 1 (ROS1), with potential antineoplastic activity. Upon oral administration, zidesamtinib targets, binds to and inhibits wild-type, point mutants and fusion proteins of ROS1. This inhibits proliferation of ROS-1-driven tumor cells, including in tumor cells harboring certain ROS1 resistance mutations, such as the solvent front mutation G2032R and the S1986Y/F, L2026M, and D2033N resistance mutations. Inhibition of ROS1 leads to the disruption of downstream signaling pathways and the inhibition of cell growth of tumors in which ROS1 overexpressed, rearranged or mutated. ROS1, overexpressed in certain cancer cells, plays a key role in cell growth and survival of cancer cells. NVL-520 is able to penetrate the blood-brain barrier (BBB).