ArticleAntimicrobial agents and chemotherapy2006
Inhibition of human immunodeficiency virus type 1 replication in latently infected cells by a novel IkappaB kinase inhibitor.
Article in Antimicrobial agents and chemotherapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 38 citations in OpenAlex.
- Block-and-Lock Approaches for HIV Cure: Mechanistic Insights, Challenges, and Emerging Role of CPSF6.International journal of molecular sciences · 2026Review
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- Role of 5-HT1A-mediated upregulation of brain indoleamine 2,3 dioxygenase 1 in the reduced antidepressant and antihyperalgesic effects of fluoxetine during maintenance treatment.Frontiers in pharmacology · 2022Article
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- The landscape of alternative splicing in HIV-1 infected CD4 T-cells.BMC medical genomics · 2020Article
- Topical Application of a Dual ABC Transporter Substrate and NF-κB Inhibitor Blocks Multiple Sources of Cutaneous Inflammation in Mouse Skin.The Journal of investigative dermatology · 2019Article
- Targeting IKKβ in Cancer: Challenges and Opportunities for the Therapeutic Utilisation of IKKβ Inhibitors.Cells · 2018Review
- The IκB kinase inhibitor ACHP strongly attenuates TGFβ1-induced myofibroblast formation and collagen synthesis.Journal of cellular and molecular medicine · 2015Article
- The role of the IKK complex in viral infections.Pathogens and disease · 2014Review
- Reactivation of latent HIV-1 by a wide variety of butyric acid-producing bacteria.Cellular and molecular life sciences : CMLS · 2012Article
- MIP-1δ activates NFATc1 and enhances osteoclastogenesis: involvement of both PLCγ2 and NFκB signaling.PloS one · 2012Article
- Effects of β(2) Agonists, Corticosteroids, and Novel Therapies on Rhinovirus-Induced Cytokine Release and Rhinovirus Replication in Primary Airway Fibroblasts.Journal of allergy · 2011Article
- Involvement of histone H3 lysine 9 (H3K9) methyltransferase G9a in the maintenance of HIV-1 latency and its reactivation by BIX01294.The Journal of biological chemistry · 2010Article
- The roles of HIV-1 proteins and antiretroviral drug therapy in HIV-1-associated endothelial dysfunction.Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2008Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In human immunodeficiency virus type 1 (HIV-1) latently infected cells, NF-kappaB plays a major role in the transcriptional induction of HIV-1 replication. Hence, downregulation of NF-kappaB activation has long been sought for effective anti-HIV therapy. Tumor necrosis factor alpha (TNF-alpha) stimulates IkappaB kinase (IKK) complex, a critical regulator in the NF-kappaB signaling pathway. A novel IKK inhibitor, ACHP {2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl-nicotinonitrile}, was developed and evaluated as a potent and specific inhibitor for IKK-alpha and IKK-beta. In this study, we examined the ability of this compound to inhibit HIV-1 replication in OM10.1 cells latently infected with HIV. When these cells were pretreated with ACHP, TNF-alpha-induced HIV-1 replication was dramatically inhibited, as measured by the HIV p24 antigen levels in the culture supernatants. Its 50% effective concentration was approximately 0.56 microM, whereas its 50% cytotoxic concentration was about 15 microM. Western blot analysis revealed inhibition of IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 nuclear translocation, and p65 phosphorylation. ACHP was also found to suppress HIV-1 long terminal repeat (LTR)-driven gene expression through the inhibition of NF-kappaB activation. Furthermore, ACHP inhibited TNF-alpha-induced NF-kappaB (p65) recruitment to the HIV-1 LTR, as assessed by chromatin immunoprecipitation assay. These findings suggest that ACHP acts as a potent suppressor of TNF-alpha-induced HIV replication in latently infected cells and that this inhibition is mediated through suppression of IKK activity.
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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.