ArticleJournal of natural products2016
Natural-Based Indirubins Display Potent Cytotoxicity toward Wild-Type and T315I-Resistant Leukemia Cell Lines.
Article in Journal of natural products, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Synthetic progress and anti-leukemic research on indirubin analogues: a review since 2010.RSC advances · 2025Review
- Indirubin, an Active Component of Indigo Naturalis, Exhibits Inhibitory Effects on Leukemia CellsAnti-cancer agents in medicinal chemistry · 2024Article
- The Fundamental Role of Oxime and Oxime Ether Moieties in Improving the Physicochemical and Anticancer Properties of Structurally Diverse Scaffolds.International journal of molecular sciences · 2023Review
- Natural Products as Anticancer Agents: Current Status and Future Perspectives.Molecules (Basel, Switzerland) · 2022Review
- Mapping insoluble indole metabolites in the gastrointestinal environment of a murine colorectal cancer model using desorption/ionisation on porous silicon imaging.Scientific reports · 2019Article
- Bromoperoxidase ProducingMarine drugs · 2019Article
- Deciphering the mechanism of Indirubin and its derivatives in the inhibition of Imatinib resistance using a "drug target prediction-gene microarray analysis-protein network construction" strategy.BMC complementary and alternative medicine · 2019Article
- Deciphering Key Pharmacological Pathways of Qingdai Acting on Chronic Myeloid Leukemia Using a Network Pharmacology-Based Strategy.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- A Systems Biology-Based Approach to Uncovering Molecular Mechanisms Underlying Effects of Traditional Chinese Medicine Qingdai in Chronic Myelogenous Leukemia, Involving Integration of Network Pharmacology and Molecular Docking Technology.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Drug resistance in chronic myelogenous leukemia (CML) requires the development of new CML chemotherapeutic drugs. Indirubin, a well-known mutikinase inhibitor, is the major active component of "Danggui Longhui Wan", a Chinese traditional medicine used for the treatment of CML symptoms. An in-house collection of indirubin derivatives was screened at 1 μM on wild-type and imatinib-resistant T315I mutant CML cells. Herein are reported that only 15 analogues of the natural 6-bromoindirubin displayed potent cytotoxicity in the submicromolar range. Kinase assays in vitro show that eight out of the 15 active molecules strongly inhibited both c-Src and Abl oncogenic kinases in the nanomolar range. Most importantly, these eight molecules blocked the activity of T315I mutant Abl kinase at the submicromolar level and with analogue 22 exhibiting inhibitory activity at the low nanomolar range. Docking calculations suggested that active indirubins might inhibit T315I Abl kinase through an unprecedented binding to both active and Src-like inactive conformations. Analogue 22 is the first derivative of a natural product identified as an inhibitor of wild-type and imatinib-resistant T315I mutant Abl kinases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.