ArticlePloS one2017
Targeting of CDK9 with indirubin 3'-monoxime safely and durably reduces HIV viremia in chronically infected humanized mice.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Natural Alkaloids as Antiviral Agents Against RNA Viruses: A Comprehensive and Mechanistic Review.Molecules (Basel, Switzerland) · 2026Review
- Synergistic Sedative Activity of Indirubin on Diazepam in Thiopental Sodium-induced Sleeping Mice: A Potential GABAergic Transmission.Molecular neurobiology · 2025Article
- Harnessing antiviral RNAi therapeutics for pandemic viruses: SARS-CoV-2 and HIV.Drug delivery and translational research · 2025Review
- Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic Pathways.ChemistryOpen · 2025Article
- Humanized mouse models for preclinical evaluation of HIV cure strategies.AIDS reviews · 2022Review
- Human Hematopoietic Stem Cell (HSC)-Engrafted NSG Mice for HIV Latency Research.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Cure and Long-Term Remission Strategies.Methods in molecular biology (Clifton, N.J.) · 2022Review
- High activation and skewed T cell differentiation are associated with low IL-17A levels in a hu-PBL-NSG-SGM3 mouse model of HIV infection.Clinical and experimental immunology · 2020Article
- P-TEFb as A Promising Therapeutic Target.Molecules (Basel, Switzerland) · 2020Review
- Reduce and Control: A Combinatorial Strategy for Achieving Sustained HIV Remissions in the Absence of Antiretroviral Therapy.Viruses · 2020Review
- Specific ActivationJournal of virology · 2019Article
- HIV Replication in Humanized IL-3/GM-CSF-Transgenic NOG Mice.Pathogens (Basel, Switzerland) · 2019Article
- Indirubin modulates CD4Journal of cellular and molecular medicine · 2019Article
- Disparate effects of cytotoxic chemotherapy on the antiviral activity of antiretroviral therapy: implications for treatments of HIV-infected cancer patients.Antiviral therapy · 2019Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Successful propagation of HIV in the human host requires entry into a permissive cell, reverse transcription of viral RNA, integration into the human genome, transcription of the integrated provirus, and assembly/release of new virus particles. Currently, there are antiretrovirals against each of these viral steps, except for provirus transcription. An inhibitor of HIV transcription could both increase potency of treatment and suppress drug-resistant strains. Cellular cyclin-dependent kinase 9 (CDK9) serves as a cofactor for the HIV Tat protein and is required for effective transcription of the provirus. Previous studies have shown that the CDK9 inhibitor Indirubin 3'-monoxime (IM) inhibits HIV transcription in vitro and in short-term in vivo studies of HIV acute infection in humanized mice (PBMC-NSG model), suggesting a therapeutic potential. The objective of this study is to evaluate the toxicity, pharmacokinetics and long-term antiviral activity of IM during chronic HIV infection in humanized mice (HSC-NSG model). We show that IM concentrations above EC50 values are rapidly achieved and sustained for > 3 h in plasma, and that non-toxic concentrations durably reduce HIV RNA levels. In addition, IM enhanced the antiviral activity of antiretrovirals from the reverse transcriptase, protease and integrase inhibitor classes in in vitro infectivity assays. In summary, IM may enhance current antiretroviral treatments and could help achieve a "functional cure" in HIV patients by preventing expression of proviruses.
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Registered trials
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