The Pharmaceutical Journal
Vol 269 No 7205 p11
6 July 2002

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Cancer Cell (www.cancercell.org)

Two potential agents for acute myeloblastic leukaemia identified

Two new agents that might be useful for the treatment of patients with acute myeloblastic leukaemia (AML) have been identified, researchers report in Cancer Cell. Both agents, CT53518 and PKC412, inhibit tyrosine kinase FLT3 receptors, mutations of which have been found in over a third of patients with AML.

Dr Louise Kelly, Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues report that CT53518 has high oral bioavailability in animal studies and a good safety profile in chronic administration. Therapeutic efficacy of CT53518 was demonstrated in a nude mouse model and in a bone marrow transplant model of AML cell lines expressing the most common mutation of FLT3. The researchers say that apoptosis was induced by CT53518 in these AML cells, a result similar to that observed when BCR/ABL-positive leukaemia cells are treated with imatinib (Glivec).

The researchers conclude that based on similar reports of efficacy of imatinib in the treatment of chronic myeloid leukaemia blast crisis, CT53518 shows great promise for treating AML patients and clinical trials are under way (2002;1:421).

Dr Ellen Weisberg, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues have also identified a potent inhibitor of the tyrosine kinase FLT3 receptor. The inhibitor, PKC412, is cytotoxic to mutant and wild-type FLT3 tyrosine kinases, as well as primary cells expressing mutant FLT3 receptors, and has potential as an antileukaemia agent, they say (ibid, p433).