CP868596 (Crenolanib) is an orally-available, benzimidazole-based inhibitor of PDGFRa and PDGFRb with IC50 values of 0.9 and 1.8 nM, respectively. Furthermore, CP868596 is active against the D842V mutant of PDGFRa, inhibiting phosphorylation at an IC50 range of 10-30 nM (wild-type PDGFRa IC50 = 10 nM). [1] Whereas imatinib, sunitinib, sorafenib, and nilotinib have little to no activity vs. this D842V mutant, CP868596 offers a novel therapy to GIST patients with this resistance.

CP868596 also shows potency (IC50 = 80 nM) against the highly sensitive H1703 cell line, suggesting single-agent therapy potential for PDGFR-driven NSCLC tumors. [2]