Bosutinib.
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Bosutinib. / von Amsberg, Gunhild; Schafhausen, Philippe; Brümmendorf, Tim.
In: Recent Results Cancer Res, Vol. 184, 2010, p. 119-127.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Bosutinib.
AU - von Amsberg, Gunhild
AU - Schafhausen, Philippe
AU - Brümmendorf, Tim
PY - 2010
Y1 - 2010
N2 - Bosutinib (SKI-606) is a 7-alkoxy-3-quinolinecarbonitrile, which functions as a dual inhibitor of Src and Abl kinases. In biochemical and proliferation assays, the compound was shown to be active against src family kinases and Bcr-Abl at IC50s of 100 and 90 nM, respectively. The bcr-abl fusion gene product, a consecutively activated tyrosine kinase, which is crucial for the development of chronic myeloid leukaemia (CML), is highly sensitive to bosutinib. Interestingly, distinctly lower concentrations of the dual src/abl inhibitor are required to ablate Bcr-Abl phosphorylation when compared to first-generation tyrosine kinase inhibitor imatinib (IM). Bosutinib is a potent inhibitor of CML cell proliferation in vitro and in vivo experiments and has demonstrated promising harbouring results in CML patients resistance or intolerance to IM in ongoing phase I/II clinical trials. Remarkably, bosutinib has been found to be capable of overcoming the majority of IM-resistant bcr-abl mutations. A randomised open label phase III clinical study to compare the efficacy of bosutinib and IM in first-line therapy of Ph+ chronic phase (CP) CML has recently been initiated. In a phase I/II clinical study with subjects suffering from advanced stages of solid tumours, long-term responses have also been reported. In conclusion, Bosutinib is a promising novel small molecule inhibitor for targeted therapy of CML and solid tumours.
AB - Bosutinib (SKI-606) is a 7-alkoxy-3-quinolinecarbonitrile, which functions as a dual inhibitor of Src and Abl kinases. In biochemical and proliferation assays, the compound was shown to be active against src family kinases and Bcr-Abl at IC50s of 100 and 90 nM, respectively. The bcr-abl fusion gene product, a consecutively activated tyrosine kinase, which is crucial for the development of chronic myeloid leukaemia (CML), is highly sensitive to bosutinib. Interestingly, distinctly lower concentrations of the dual src/abl inhibitor are required to ablate Bcr-Abl phosphorylation when compared to first-generation tyrosine kinase inhibitor imatinib (IM). Bosutinib is a potent inhibitor of CML cell proliferation in vitro and in vivo experiments and has demonstrated promising harbouring results in CML patients resistance or intolerance to IM in ongoing phase I/II clinical trials. Remarkably, bosutinib has been found to be capable of overcoming the majority of IM-resistant bcr-abl mutations. A randomised open label phase III clinical study to compare the efficacy of bosutinib and IM in first-line therapy of Ph+ chronic phase (CP) CML has recently been initiated. In a phase I/II clinical study with subjects suffering from advanced stages of solid tumours, long-term responses have also been reported. In conclusion, Bosutinib is a promising novel small molecule inhibitor for targeted therapy of CML and solid tumours.
KW - Animals
KW - Humans
KW - Clinical Trials as Topic
KW - inhibitors
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
KW - Neoplasms drug therapy
KW - Aniline Compounds pharmacology
KW - Fusion Proteins, bcr-abl antagonists
KW - Nitriles pharmacology
KW - Oncogene Proteins v-abl antagonists
KW - Protein Kinase Inhibitors therapeutic use
KW - Quinolines pharmacology
KW - Animals
KW - Humans
KW - Clinical Trials as Topic
KW - inhibitors
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
KW - Neoplasms drug therapy
KW - Aniline Compounds pharmacology
KW - Fusion Proteins, bcr-abl antagonists
KW - Nitriles pharmacology
KW - Oncogene Proteins v-abl antagonists
KW - Protein Kinase Inhibitors therapeutic use
KW - Quinolines pharmacology
M3 - SCORING: Zeitschriftenaufsatz
VL - 184
SP - 119
EP - 127
JO - Recent Results Cancer Res
JF - Recent Results Cancer Res
SN - 0080-0015
ER -