articleBloodAug 5, 2009BRONZE OA

AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML)

PPPatrick P. ZarrinkarRNRuwanthi N. GunawardaneMCMerryl CramerMFMichael F. GardnerDBDaniel Brigham

Johns Hopkins University · Sidney Kimmel Comprehensive Cancer Center

PubMed
Indexed incrossrefdatacitepubmed

Abstract

Activating mutations in the receptor tyrosine kinase FLT3 are present in up to approximately 30% of acute myeloid leukemia (AML) patients, implicating FLT3 as a driver of the disease and therefore as a target for therapy. We report the characterization of AC220, a second-generation FLT3 inhibitor, and a comparison of AC220 with the first-generation FLT3 inhibitors CEP-701, MLN-518, PKC-412, sorafenib, and sunitinib. AC220 exhibits low nanomolar potency in biochemical and cellular assays and exceptional kinase selectivity, and in animal models is efficacious at doses as low as 1 mg/kg given orally once daily. The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties…

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Topics & keywords

Topics
Keywords
  • Potency
  • Myeloid leukemia
  • Fms-Like Tyrosine Kinase 3
  • Sorafenib
  • Pharmacology
  • Sunitinib
  • Chemistry
  • Tyrosine-kinase inhibitor
UN Sustainable Development Goals
  • Good health and well-being
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