Crenolanib (CP-868596) is a potent, specific, and orally available inhibitor of PDGFRα, PDGFRβ and FLT3 with inhibitor-binding constant (Kd) of 3.2, 2.1, and 0.74 nM, respectively [1].
It has been shown that crenolanib is more potent than quizartinib and sorafenib at blocking FLT3 autophosphorylation and causing cytotoxicity [2]. Crenolanib is confirmed to be100-fold more potent than imatinib at suppressing D842V mutation. In addition, it has been reported that crenolanib inhibits PDGFRα D842V mutation rather than V561D mutation, with IC50 value?of 10 nM [1]. In EOL-1 cells, crenolanib also inhibits the FIP1L1-PDGFRA fusion kinase activity (IC50=1 nM) and cell proliferation (IC50= 0.2 pM)[1].
References:
[1] Heinrich MC1,?Griffith D,?McKinley A,?Patterson J,?Presnell A,?Ramachandran A,?Debiec-Rychter M.
Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res.?2012 Aug 15;18(16):4375-84.
[2] Galanis A1,?Ma H,?Rajkhowa T,?Ramachandran A,?Small D,?Cortes J,?Levis M. Crenolanib?is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood.?2014 Jan 2;123(1):94-100.
