126433-42-9Relevant articles and documents
Enhancing effect of indirubin derivatives on 1,25-dihydroxyvitamin D3- and all-trans retinoic acid-induced differentiation of HL-60 leukemia cells
Kim, Seung Hyun,Kim, Si-Wouk,Choi, Soo Jeong,Kim, Yong-Chul,Kim, Tae Sung
, p. 6752 - 6758 (2006)
The induction of differentiation represents a new and promising approach to cancer therapy, well illustrated by the treatment of acute promyelocytic leukemia (APL) with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (ATRA). Using combinations of low, nontoxic concentrations of either 1,25-(OH)2D3 or ATRA and differentiation-enhancing chemicals, adverse effects such as hypercalcemic effects have been ameliorated, and long-term survival has been improved. Indirubin has been demonstrated to exert anti-leukemic effects in cases of chronic myelocytic leukemia. Previously, we synthesized a series of indirubin derivatives and evaluated their anti-proliferative properties against cancer cells. In this study, we determined the enhancing activities of these derivatives on 1,25-(OH)2D3- and ATRA-induced differentiation of human promyelocytic leukemia HL-60 cells. Importantly, some of these derivatives were found to synergistically enhance the differentiation of HL-60 cells in a concentration-dependent manner when coupled with low doses of either 1,25-(OH)2D3 or ATRA. The ability of indirubin derivatives to enhance the differentiation potential of 1,25-(OH)2D3 or ATRA may improve the ultimate outcomes of APL therapy.
Synthesis and structure-activity relationships of novel indirubin derivatives as potent anti-proliferative agents with CDK2 inhibitory activities
Moon, Myoung Ju,Lee, Sang Kook,Lee, Jong-Won,Song, Woo Keun,Kim, Si Wouk,Kim, Jae Il,Cho, Chunghee,Choi, Soo Jeong,Kim, Yong-Chul
, p. 237 - 246 (2006)
Indirubin, an active ingredient of a traditional Chinese recipe Danggui Longhui Wan, has been known as a CDK inhibitor competing with ATP for binding to the catalytic site of cyclin-dependent kinases (CDKs). Since CDKs, a group of serine/threonine kinases forming active heterodimeric complexes with cyclins, are key regulators of the cell cycle regulation, therapeutic interventions targeting CDKs have been stimulated for the treatment of proliferative diseases, such as cancer, psoriasis, and for the prevention of chemotherapy-associated side effects, such as alopecia. A series of novel indirubin analogs was synthesized and evaluated for anti-proliferative and CDK2 inhibitory activities. Among the indirubin derivatives tested in the growth inhibitions against several human cancer cell lines, 5-nitro, halide, and bulky group containing acylamino substituted analogs showed high anti-proliferative effects. Selected analogs showing potent anti-proliferative activities were evaluated further in the CDK2 enzyme assay, which resulted in the discovery of potent CDK2 inhibitors.
Indirubin Derivatives as Dual Inhibitors Targeting Cyclin-Dependent Kinase and Histone Deacetylase for Treating Cancer
An, Jianxiong,Cao, Zhuoxian,Gu, Zhicheng,He, Bin,Li, Yan,Li, Yongjun,Lin, Hening,Lin, Shuxian,Liu, Ting,Wang, Jie,Wang, Pan,Yang, Fenfen,Zhao, Yonglong
, p. 15280 - 15296 (2021/10/25)
To utilize the unique scaffold of a natural product indirubin, we herein adopted the strategy of combined pharmacophores to design and synthesize a series of novel indirubin derivatives as dual inhibitors against cyclin-dependent kinase (CDK) and histone deacetylase (HDAC). Among them, the lead compound 8b with remarkable CDK2/4/6 and HDAC6 inhibitory activity of IC50 = 60.9 ± 2.9, 276 ± 22.3, 27.2 ± 4.2, and 128.6 ± 0.4 nM, respectively, can efficiently induce apoptosis and S-phase arrest in several cancer cell lines. In particular, compound 8b can prevent the proliferation of a non-small-cell lung cancer cell line (A549) through the Mcl-1/XIAP/PARP axis, in agreement with the unique modes of action of the combined agents of HDAC inhibitors and CDK inhibitors. In an A549 xerograph model, compound 8b showed significant antitumor efficacy correlated with its dual inhibition. Our data demonstrated that compound 8b as a single agent could be a promising drug candidate for cancer therapy in combination with CDK and HDAC inhibitors.
Composition for Inhibiting or Treating for Acute Myeloid Leukemia or Metastatic Breast Cancer
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Paragraph 0064; 0074-0078, (2021/05/11)
The present invention relates to a pharmaceutical composition for preventing or treating acute myeloid leukemia or metastatic breast cancer comprising an indirubin derivative as an active ingredient. Use of the composition of the invention effectively inhibits the activity of FLT3 kinase. A composition for preventing or treating acute myeloid leukemia or metastatic breast cancer is provided.
INDIRUBIN DERIVATIVES HAVING ANTICANCER PROPERTY AGAINST HUMAN CANCER CELL ME
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Page/Page column 16, (2008/06/13)
The present invention relates to an indirubin derivative having anticancer property by inhibiting cell proliferation as to human cancer cell line. More particularly, this invention provides the synthesis of indirubin derivative known as CDK(Cyclin-dependent kinase) inhibitor. Further, inhibition activity of proliferation as to human cancer cell line and apoptosis against induced-differentiation of said indirubin derivative are researched to develop a novel indirubin derivative having efficacious anticancer properties as to various human cell lines.
Use of cell membrane penetrating indigoid bisindole derivatives
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Page column 4, (2008/06/13)
The present invention relates to the use of cell membrane penetrating indigoid bisindole derivatives for the manufacture of a medicament for the treatment of human solid cancers.
