Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571)

Paul La Rosée, Amie S. Corbin, Eric P. Stoffregen, Michael W. Deininger, Brian Druker

Research output: Contribution to journalArticle

197 Citations (Scopus)

Abstract

Imatinib mesylate, a selective inhibitor of the Abl tyrosine kinase, is effective as a single-agent therapy for chronic myelogenous leukemia. However, resistance has been reported, particularly in patients with advanced-stage disease. Mutations within the Abl kinase domain are a major cause of resistance, demonstrating that Bcr-Abl remains a critical drug target. Recently, a novel pyrido[2,3-d]pyrimidine derivative, PD180970, has been shown to potently inhibit Bcr-Abl and induce apoptosis in Bcr-Abl-expressing leukemic cells. We analyzed the inhibitory activity of PD180970 against Abl kinase domain mutations and cells expressing clinically relevant mutations. Our data indicate that PD180970 is active against several Bcr-Abl mutations that are resistant to imatinib and support the notion that developing additional Abl kinase inhibitors would be useful as a treatment strategy for chronic myelogenous leukemia.

Original languageEnglish (US)
Pages (from-to)7149-7153
Number of pages5
JournalCancer Research
Volume62
Issue number24
StatePublished - Dec 15 2002

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Protein Isoforms
Phosphotransferases
Mutation
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Apoptosis
PD 180970
Imatinib Mesylate
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571). / La Rosée, Paul; Corbin, Amie S.; Stoffregen, Eric P.; Deininger, Michael W.; Druker, Brian.

In: Cancer Research, Vol. 62, No. 24, 15.12.2002, p. 7149-7153.

Research output: Contribution to journalArticle

La Rosée, Paul ; Corbin, Amie S. ; Stoffregen, Eric P. ; Deininger, Michael W. ; Druker, Brian. / Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571). In: Cancer Research. 2002 ; Vol. 62, No. 24. pp. 7149-7153.
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