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Association details:
Evidence:
Evidence Level:
Sensitive: D – Preclinical
New
Title:

Potent Activity of Ponatinib (AP24534) in Models of FLT3-Driven Acute Myeloid Leukemia and Other Hematologic Malignancies

Excerpt:
Ponatinib inhibited phosphorylation of all 4 RTKs in a dose-dependent manner, with IC50 values between 0.3 to 20 nmol/L (Fig. 2A and Table 1)….ponatinib is a multitargeted kinase inhibitor that displays potent inhibition of FLT3 and is cytotoxic to AML cells harboring the FLT3-ITD mutation. Importantly, this agent exhibits activity against additional RTKs, FGFR1, KIT, and PDGFRα, which have also been shown to play roles in the pathogenesis of hematologic malignancies. Notably, the potency of ponatinib against these RTKs in vitro and plasma levels of ponatinib observed in humans suggest that ponatinib may have clinical activity against these targets.
DOI:
10.1158/1535-7163.MCT-10-1044