Definition

An orally bioavailable pan-inhibitor of the mutated forms of the tumor-associated antigen (TAA) receptor tyrosine kinase mast/stem cell factor receptor c-Kit (SCFR), with potential antineoplastic activity. Upon oral administration, pan-variant KIT inhibitor THE-630 targets, binds to and inhibits the activity of all known, clinically relevant KIT activating and resistance mutations in gastrointestinal stromal tumors (GIST). More specifically, THE-630 inhibits the primary activating mutations deletion in Ex11 (Ex11Del) and insertion in Ex9 (Ex9Ins); the secondary resistance mutations, including the ATP binding pocket mutants V654A and T670I and the activation loop mutants D816G/H, D820A/G, N822K, Y823D, and A829P. This inhibits KIT-mediated signaling and the proliferation of tumor cells that overexpress c-Kit mutations. c-Kit is mutated in various tumor cell types and plays a key role in the regulation of cellular proliferation and resistance to chemotherapy.