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 language | English (US) |
|---|---|
| Pages (from-to) | 7149-7153 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 62 |
| Issue number | 24 |
| State | Published - Dec 15 2002 |
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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 journal › Article
}
TY - JOUR
T1 - Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571)
AU - La Rosée, Paul
AU - Corbin, Amie S.
AU - Stoffregen, Eric P.
AU - Deininger, Michael W.
AU - Druker, Brian
PY - 2002/12/15
Y1 - 2002/12/15
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0037115644&partnerID=8YFLogxK
M3 - Article
C2 - 12499247
AN - SCOPUS:0037115644
VL - 62
SP - 7149
EP - 7153
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 24
ER -