Bosutinib: a dual SRC/ABL kinase inhibitor for the treatment of chronic myeloid leukemia
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Bosutinib: a dual SRC/ABL kinase inhibitor for the treatment of chronic myeloid leukemia. / Keller, Gunhild; Schafhausen, Philippe; Brummendorf, Tim H.
in: EXPERT REV HEMATOL, Jahrgang 2, Nr. 5, 01.10.2009, S. 489-97.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Bosutinib: a dual SRC/ABL kinase inhibitor for the treatment of chronic myeloid leukemia
AU - Keller, Gunhild
AU - Schafhausen, Philippe
AU - Brummendorf, Tim H
PY - 2009/10/1
Y1 - 2009/10/1
N2 - The tyrosine kinase inhibitor imatinib mesylate (IM) set new standards in the treatment of chronic myeloid leukemia (CML). However, emergence of resistance to IM became a major therapeutic challenge. Bosutinib (SKI-606), a 7-alkoxy-3-quinolinecarbonitrile, functions as a dual inhibitor of SRC and ABL kinases, and preclinical studies demonstrated a high antiproliferative activity in human and murine CML cell lines. In ongoing Phase I/II clinical trials, bosutinib yielded promising results revealing high clinical efficacy, good tolerability and reduced toxicity in IM-resistant or -intolerant CML patients. In this article, we provide an overview on the mechanism of action, and the preclinical and currently available clinical data for bosutinib. Owing to its favorable toxicity profile and its high antileukemic activity, bosutinib is a promising novel treatment option for patients with CML. A recently initiated, randomized open-label Phase III clinical study will clarify its role in first-line therapy of Philadelphia chromosome-positive chronic-phase CML.
AB - The tyrosine kinase inhibitor imatinib mesylate (IM) set new standards in the treatment of chronic myeloid leukemia (CML). However, emergence of resistance to IM became a major therapeutic challenge. Bosutinib (SKI-606), a 7-alkoxy-3-quinolinecarbonitrile, functions as a dual inhibitor of SRC and ABL kinases, and preclinical studies demonstrated a high antiproliferative activity in human and murine CML cell lines. In ongoing Phase I/II clinical trials, bosutinib yielded promising results revealing high clinical efficacy, good tolerability and reduced toxicity in IM-resistant or -intolerant CML patients. In this article, we provide an overview on the mechanism of action, and the preclinical and currently available clinical data for bosutinib. Owing to its favorable toxicity profile and its high antileukemic activity, bosutinib is a promising novel treatment option for patients with CML. A recently initiated, randomized open-label Phase III clinical study will clarify its role in first-line therapy of Philadelphia chromosome-positive chronic-phase CML.
KW - Aniline Compounds
KW - Animals
KW - Antineoplastic Agents
KW - Clinical Trials as Topic
KW - Drug Evaluation, Preclinical
KW - Fusion Proteins, bcr-abl
KW - Humans
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive
KW - Nitriles
KW - Protein Kinase Inhibitors
KW - Proto-Oncogene Proteins c-abl
KW - Quinolines
KW - src-Family Kinases
U2 - 10.1586/ehm.09.42
DO - 10.1586/ehm.09.42
M3 - SCORING: Journal article
C2 - 21083014
VL - 2
SP - 489
EP - 497
JO - EXPERT REV HEMATOL
JF - EXPERT REV HEMATOL
SN - 1747-4086
IS - 5
ER -