ArticleScientific reports2018
BI-2536 and BI-6727, dual Polo-like kinase/bromodomain inhibitors, effectively reactivate latent HIV-1.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Consensus Pharmacological Interactions for PLK2 Inhibitor Identification in Colorectal Cancer Treatment.Journal of chemical information and modeling · 2026Article
- Prognostic value and experimental validation of atherosclerosis-derived pathogenic genes in colorectal cancer.Frontiers in oncology · 2025Article
- Characteristics and mechanisms of latency-reversing agents in the activation of the human immunodeficiency virus 1 reservoir.Archives of virology · 2023Review
- Polo-like kinase inhibitor BI2536 induces eryptosis.Wiener medizinische Wochenschrift (1946) · 2023Article
- Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation.Molecules (Basel, Switzerland) · 2022Review
- Exploitation and Verification of a Stroma- and Metastasis-Associated Risk Prognostic Signature in Pancreatic Adenocarcinoma.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Insights Into Persistent HIV-1 Infection and Functional Cure: Novel Capabilities and Strategies.Frontiers in microbiology · 2022Review
- U1 and OM10.1. Myeloid Cell Lines as Surrogate Models of Reversible Proviral Latency.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Inhibition of polo-like kinase 1 (PLK1) facilitates reactivation of gamma-herpesviruses and their elimination.PLoS pathogens · 2021Article
- Knowledge From London and Berlin: Finding Threads to a Functional HIV Cure.Frontiers in immunology · 2021Review
- Diversity of small molecule HIV-1 latency reversing agents identified in low- and high-throughput small molecule screens.Medicinal research reviews · 2020Review
- In Depth Analysis of Kinase Cross Screening Data to Identify CAMKK2 Inhibitory Scaffolds.Molecules (Basel, Switzerland) · 2020Article
- HIV-1 DNA-capture-seq is a useful tool for the comprehensive characterization of HIV-1 provirus.Scientific reports · 2019Article
- Designing Dual Inhibitors of Anaplastic Lymphoma Kinase (ALK) and Bromodomain-4 (BRD4) by Tuning Kinase Selectivity.Journal of medicinal chemistry · 2019Article
- Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs.Frontiers in microbiology · 2019Review
- Discovery and Development of Anti-HIV Therapeutic Agents: Progress Towards Improved HIV Medication.Current topics in medicinal chemistry · 2019Review
- Harnessing host-virus evolution in antiviral therapy and immunotherapy.Clinical & translational immunology · 2019Review
- Barriers for HIV Cure: The Latent Reservoir.AIDS research and human retroviruses · 2018Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIV-1 latent reservoirs harbouring silenced but replication-competent proviruses are a major obstacle against viral eradication in infected patients. The "shock and kill" strategy aims to reactivate latent provirus with latency reversing agents (LRAs) in the presence of antiretroviral drugs, necessitating the development of effective and efficient LRAs. We screened a chemical library for potential LRAs and identified two dual Polo-like kinase (PLK)/bromodomain inhibitors, BI-2536 and BI-6727 (volasertib), which are currently undergoing clinical trials against various cancers. BI-2536 and BI-6727 significantly reactivated silenced HIV-1 provirus at both the mRNA and protein level in two latently infected model cell lines (ACH2 and U1). BI-2536 dramatically reactivated transcription of latent HIV-1 provirus in peripheral blood mononuclear cells derived from infected patients. Long terminal repeat activation by the inhibitors was associated with bromodomain rather than PLK inhibition. We also found that BI-2536 synergistically activates the latent provirus in combination with SAHA, a histone deacetylase inhibitor, or the non-tumour-promoting phorbol ester prostratin. Our findings strongly suggest that BI-2536 and BI-6727 are potent LRAs for the "shock and kill" HIV-1 eradication strategy.
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