5'-OH-5-nitro-Indirubin oxime (AGM130), an Indirubin derivative, induces apoptosis of Imatinib-resistant chronic myeloid leukemia cells.

Abstract

Imatinib is a highly effective drug for the treatment of chronic myeloid leukemia (CML) that targets the BCR-ABL kinase. However, a number of patients have CML that is resistant to Imatinib treatment. In this report, we developed AGM130 as a potential therapeutic drug for Imatinib-resistant CML treatment. The AGM130 compound is derived from Indirubin, which is an ingredient of Danggui Longhui Wan and known as a cyclin-dependent kinase (CDK) inhibitor. The water solubility of AGM130 is more enhanced than that of the original form of Indirubin, which has very poor water solubility. Our data showed that the AGM130 compound efficiently decreased the viability of CML-derived K562 cells. Moreover, this compound also efficiently decreased the viability of Imatinib-resistant K562 cells in in vitro and in vivo systems. In addition, like Indirubin, AGM130 also inhibited phosphorylation of retinoblastoma protein (Rb), which is a major substrate of CDK. Conclusively, our data suggest that AGM130 is a strong candidate for treating Imatinib-resistant CML.

• Authors: Woo-Seok Kim, Min-Jung Lee, Do-Hyung Kim, Jung-Eun Lee, Jae-Il Kim, Yong-Chul Kim, Mi-Ryoung Song, Sung-Gyoo Park
• Journal: Leukemia research (Leuk Res) Vol. 37 Issue 4 Pg. 427-33 (Apr 2013) ISSN: 1873-5835 [Electronic] England
• PMID: 23337400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Benzamides
• Piperazines
• Pyrimidines
• Imatinib Mesylate
• Idarubicin

Topics

• Apoptosis (drug effects)
• Benzamides
• Humans
• Idarubicin (analogs & derivatives, pharmacology)
• Imatinib Mesylate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, pathology)
• Piperazines (pharmacology, therapeutic use)
• Pyrimidines (pharmacology, therapeutic use)