Evidence map›Paper›PMID 27347680›Full record

ArticlePloS one2016

Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis.

Eric Lefebvre, Graeme Moyle, Ran Reshef, Lee P Richman, Melanie Thompson, Feng Hong, Hsin-L Chou, Taishi Hashiguchi, Craig Plato, Dominic Poulin and 5 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02217475 (CENTAUR), which is not on this map. Cited by 160 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 2 pooled it
27.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

NCT02217475 phase2completednot on this map

CENTAUR: Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Subjects With Liver Fibrosis

TypeinterventionalSponsorTobira Therapeutics, Inc.Ran2014 to 2017Enrolled289ConditionsNonalcoholic SteatohepatitisArmsCenicriviroc, Placebo
3 · Its place in the literature

Who cites it

160 citing papers in PubMed, 2 syntheses or guidelines pooled it, 308 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Improvement in Hepatic Fibrosis Biomarkers Associated With Chemokine Receptor Inactivation Through Mutation or Therapeutic Blockade.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019
    Trial
  5. Trial
  6. Trial
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Targeting macrophages in liver fibrosis.Frontiers in immunology · 2026
    Review
  16. Review
  17. Article
  18. Fibrogenic Gene Signature as Early Prediction for the Efficacy of Pharmacological Interventions for MASH-Associated Fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  19. Review
  20. Article

100 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 8 institutions in 3 countries.

Eric LefebvreTobira Therapeutics, Inc., South San Francisco, CA, United States of America.
Graeme MoyleChelsea and Westminster Hospital, London, United Kingdom.
Ran ReshefColumbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, United States of America.
Lee P RichmanDepartment of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States of America.
Melanie ThompsonAIDS Research Consortium of Atlanta, Atlanta, GA, United States of America.
Feng HongDivision of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Hsin-L ChouDivision of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Taishi HashiguchiStelic Institute & Co., Inc., Tokyo, Japan.
Craig PlatoPlato BioPharma, Inc., Westminster, CO, United States of America.
Dominic PoulinCharles River Laboratories Montreal ULC, Montreal, QC, Canada.
Toni RichardsPlato BioPharma, Inc., Westminster, CO, United States of America.
Hiroyuki YoneyamaStelic Institute & Co., Inc., Tokyo, Japan.
Helen JenkinsTobira Therapeutics, Inc., South San Francisco, CA, United States of America.
Grushenka WolfgangIndependent Consultant, Kailua-Kona, HI, United States of America.
Scott L FriedmanDivision of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Icahn School of Medicine at Mount Sinai · USARCA Biopharma (United States) · USNkarta Therapeutics (United States) · USStelic (Japan) · JPAIDS Research Consortium of Atlanta · USChelsea and Westminster Hospital · GBColumbia University Irving Medical Center · USUniversity of Pennsylvania · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007170 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BRASS, LAWRENCE F · 1985 to 2022
$54.0M
NIGMS NIH HHS T32 GM007170
6 · The paper itself

Abstract

BACKGROUND &

aimsInteractions between C-C chemokine receptor types 2 (CCR2) and 5 (CCR5) and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC) is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVC's anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis.

methodsMonocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVC's antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH) and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic gene and protein expression, and pharmacokinetic analyses.

resultsCVC significantly reduced monocyte/macrophage recruitment in vivo at doses ≥20 mg/kg/day (p < 0.05). At these doses, CVC showed antifibrotic effects, with significant reductions in collagen deposition (p < 0.05), and collagen type 1 protein and mRNA expression across the three animal models of fibrosis. In the NASH model, CVC significantly reduced the non-alcoholic fatty liver disease activity score (p < 0.05 vs. controls). CVC treatment had no notable effect on body or liver/kidney weight.

conclusionsCVC displayed potent anti-inflammatory and antifibrotic activity in a range of animal fibrosis models, supporting human testing for fibrotic diseases. Further experimental studies are needed to clarify the underlying mechanisms of CVC's antifibrotic effects. A Phase 2b study in adults with NASH and liver fibrosis is fully enrolled (CENTAUR Study 652-2-203; NCT02217475).

Indexed as

AnimalsCCR5 Receptor AntagonistsChemotaxisFibrosisImidazolesKidney DiseasesMacrophagesMaleMiceMice, Inbred C57BLMonocytesNon-alcoholic Fatty Liver DiseaseRatsRats, Sprague-DawleyReceptors, CCR2SulfoxidesCCR5 Receptor AntagonistscenicrivirocImidazolesReceptors, CCR2Sulfoxides

Identifiers

PMID27347680
PMCPMC4922569
OpenAlexW2467384826

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.