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Tandutinib, an oral, small-molecule inhibitor of FLT3 for the treatment of AML and other cancer indications.

Abstract
An improved understanding of acute myelogenous leukemia (AML) over the past two decades has led to a characterization of associated recurring cytogenetic abnormalities. AML is often driven by the overexpression or constitutive activation of receptor tyrosine kinases such as Fms-like tyrosine kinase 3 (FLT3), which serves as a good therapeutic target. Millennium Pharmaceuticals Inc's tandutinib (MLN-518) is an orally active inhibitor of FLT3 kinase and family members PDGFR beta and c-Kit. Tandutinib inhibited FLT3 phosphorylation, downstream signaling and malignant growth in vitro and in animal models. The drug exhibited limited activity as a single agent in phase I and II clinical trials in patients with AML and myelodysplastic syndrome, but displayed promising antileukemic activity (90% complete remissions) in a phase I/II trial in patients with newly diagnosed AML when administered in combination with cytarabine and daunorubicin. Phase II clinical trials for tandutinib are ongoing in patients with AML or renal cell carcinoma.
AuthorsYuan Cheng, Keren Paz
JournalIDrugs : the investigational drugs journal (IDrugs) Vol. 11 Issue 1 Pg. 46-56 (Jan 2008) ISSN: 1369-7056 [Print] England
PMID18175263 (Publication Type: Journal Article, Review)
Chemical References
  • Piperazines
  • Quinazolines
  • tandutinib
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
Topics
  • Administration, Oral
  • Animals
  • Clinical Trials as Topic
  • Humans
  • Leukemia, Myeloid, Acute (drug therapy)
  • Piperazines (administration & dosage, therapeutic use)
  • Quinazolines (administration & dosage, therapeutic use)
  • fms-Like Tyrosine Kinase 3 (antagonists & inhibitors)

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