2. Academic Validation
  3. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML)

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

  • Blood. 2009 Oct 1;114(14):2984-92. doi: 10.1182/blood-2009-05-222034.
Patrick P Zarrinkar 1,  Ruwanthi N Gunawardane,  Merryl D Cramer,  Michael F Gardner,  Daniel Brigham,  Barbara Belli,  Mazen W Karaman,  Keith W Pratz,  Gabriel Pallares,  Qi Chao,  Kelly G Sprankle,  Hitesh K Patel,  Mark Levis,  Robert C Armstrong,  Joyce James,  Shripad S Bhagwat
Affiliations

Affiliation

  • 1 Ambit Biosciences, San Diego, CA 92121, USA. pzarrinkar@ambitbio.com
PMID: 19654408 DOI: 10.1182/blood-2009-05-222034
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 is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 Inhibitor.

Figures
Products