ArticleJournal of virology2004
Spirodiketopiperazine-based CCR5 inhibitor which preserves CC-chemokine/CCR5 interactions and exerts potent activity against R5 human immunodeficiency virus type 1 in vitro.
Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 221 citations in OpenAlex.
- Trial
- Virologic failure in first-line human immunodeficiency virus therapy with a CCR5 entry inhibitor, aplaviroc, plus a fixed-dose combination of lamivudine-zidovudine: nucleoside reverse transcriptase inhibitor resistance regardless of envelope tropism.Antimicrobial agents and chemotherapy · 2009Trial
- Hepatotoxicity observed in clinical trials of aplaviroc (GW873140).Antimicrobial agents and chemotherapy · 2008Trial
- Pharmacokinetics and short-term safety of 873140, a novel CCR5 antagonist, in healthy adult subjects.Antimicrobial agents and chemotherapy · 2005Trial
- Chemokine receptor type-5: a key regulator of immunity, disease pathogenesis, and emerging therapeutic target.Inflammopharmacology · 2025Review
- The chemokine receptor CCR5: multi-faceted hook for HIV-1.Retrovirology · 2024Review
- RETRACTED: The Discovery of Novel Antimicrobial Agents through the Application of Isocyanide-Based Multicomponent Reactions.Antibiotics (Basel, Switzerland) · 2023Review
- Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold.Biomolecules · 2021Review
- HIV-1 Entry and Membrane Fusion Inhibitors.Viruses · 2021Review
- Antibody Conjugates for Targeted Therapy Against HIV-1 as an Emerging Tool for HIV-1 Cure.Frontiers in immunology · 2021Review
- Activity and structural analysis of GRL-117C: a novel small molecule CCR5 inhibitor active against R5-tropic HIV-1s.Scientific reports · 2019Article
- Discovery and Development of Anti-HIV Therapeutic Agents: Progress Towards Improved HIV Medication.Current topics in medicinal chemistry · 2019Review
- CCR5 RNA Pseudoknots: Residue and Site-Specific Labeling correlate Internal Motions with microRNA Binding.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
- "Fusion and binding inhibition" key target for HIV-1 treatment and pre-exposure prophylaxis: targets, drug delivery and nanotechnology approaches.Drug delivery · 2017Review
- What Do Structures Tell Us About Chemokine Receptor Function and Antagonism?Annual review of biophysics · 2017Review
- Molecular Mechanism of Action for Allosteric Modulators and Agonists in CC-chemokine Receptor 5 (CCR5).The Journal of biological chemistry · 2016Article
- Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5.Pharmacology research & perspectives · 2016Article
- Rational and combinatorial tailoring of bioactive cyclic dipeptides.Frontiers in microbiology · 2015Review
- Gating function of isoleucine-116 in TM-3 (position III:16/3.40) for the activity state of the CC-chemokine receptor 5 (CCR5).British journal of pharmacology · 2014Article
- International Union of Basic and Clinical Pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors.Pharmacological reviews · 2014Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
We identified a novel spirodiketopiperazine (SDP) derivative, AK602/ONO4128/GW873140, which specifically blocked the binding of macrophage inflammatory protein 1alpha (MIP-1alpha) to CCR5 with a high affinity (K(d) of approximately 3 nM), potently blocked human immunodeficiency virus type 1 (HIV-1) gp120/CCR5 binding and exerted potent activity against a wide spectrum of laboratory and primary R5 HIV-1 isolates, including multidrug-resistant HIV-1 (HIV-1(MDR)) (50% inhibitory concentration values of 0.1 to 0.6 nM) in vitro. AK602 competitively blocked the binding to CCR5 expressed on Chinese hamster ovary cells of two monoclonal antibodies, 45523, directed against multidomain epitopes of CCR5, and 45531, specific against the C-terminal half of the second extracellular loop (ECL2B) of CCR5. AK602, despite its much greater anti-HIV-1 activity than other previously published CCR5 inhibitors, including TAK-779 and SCH-C, preserved RANTES (regulated on activation normal T-cell expressed and secreted) and MIP-1beta binding to CCR5(+) cells and their functions, including CC-chemokine-induced chemotaxis and CCR5 internalization, while TAK-779 and SCH-C fully blocked the CC-chemokine/CCR5 interactions. Pharmacokinetic studies revealed favorable oral bioavailability in rodents. These data warrant further development of AK602 as a potential therapeutic for HIV-1 infection.
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What OpenQuestion holds
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.