NEW YORK (Reuters Health) - A novel ABL kinase inhibitor, designated BMS-354825, is active against tumor cells resistant to imatinib and prolongs the survival of mice harboring such cells, US researchers report.
Imatinib, which is marketed by Novartis Pharmaceuticals under the trade name Gleevec or Glivec, has proven to be an effective agent for inducing remission in patients with chronic myeloid leukemia. However, resistance to the drug appears to be on the rise.
Resistance to imatinib occurs when tumor cells acquire BCR-ABL kinase domain mutations that prevent the drug from binding, according to the report published in the July 16th issue of Science.
Dr. Charles L. Sawyers, from the University of California in Los Angeles, and colleagues were interested in BMS-354825, a synthetic orally bioavailable agent, because it appeared to have less stringent binding requirements than imatinib. Therefore, the new drug might be relatively immune to the mutations that render imatinib ineffective.
In laboratory studies, BMS-354825 displayed two-log increased potency compared with imatinib, the researchers note. Moreover, the drug showed activity against 14 of 15 imatinib-resistant BCR-ABL mutants.
Treatment with BMS-354825 increased the survival of mice with BCR-ABL-driven disease. In addition, the drug blocked the proliferation of bone marrow progenitor cells obtained from patients with imatinib-sensitive and -resistant leukemia.
“On the basis of the preclinical results described here,” the investigators conclude, “the clinical safety and efficacy of BMS-354825 is currently being evaluated in a phase I clinical trial in chronic myeloid leukemia patients with imatinib resistance.”
BMS-354825 is being developed by Princeton, New Jersey-based Bristol-Myers Squibb.
Source: Science 2004;305:399-401. [ Google search on this article ]
Copyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
