Indirubin derivatives and uses thereof in treating chronic myelogenous leukemia
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United States of America Patent
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Dec 6, 2016
Grant Date -
Aug 15, 2013
app pub date -
Feb 4, 2013
filing date -
Feb 3, 2012
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Abstract
Indirubin is the major active anti-tumor component of a traditional Chinese herbal medicine used for treatment of chronic myelogenous leukemia (CML). One aspect of the invention relates to a method of treating CML using at least one indirubin derivative compound or a pharmaceutical composition thereof. Indirubin derivatives (IRDs) potently inhibited Signal Transducer and Activator of Transcription 5 (Stat5) protein in CML cells. Compound IRD 810 inhibits Bcr-Abl/Stat5 or Src/Stat5 signaling in human KCL-22 CML and imatinib-resistant human KCL-22 CML cells expressing the T315I mutant Bcr-Abl. Previous studies indicate that SFKs cooperate with Bcr-Abl to activate downstream Stat5 signaling. Activation of Stat5 was strongly blocked by IRD 810 in CML cells. IRDs disclosed herein have been identified as potent inhibitors of Bcr-Abl/Stat5 or SFK/Stat5 signaling pathway. IRDs disclosed herein are new therapeutics for wild type or T315I mutant Bcr-Abl-positive CML patients, and may also treat other solid tumors, including prostate cancer and lymphoma.
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