What Is Rencofilstat? Definition and What Research Reports

Rencofilstat (development code CRV431) is an orally administered cyclophilin inhibitor: a macrocyclic molecule chemically derived from cyclosporine A that binds cyclophilin proteins but was engineered to avoid the calcineurin-mediated immunosuppression associated with its parent compound. It has been studied mainly in liver disease — non-alcoholic steatohepatitis (NASH), now more commonly termed metabolic dysfunction-associated steatohepatitis (MASH) — and in virology and oncology models. Rencofilstat is an investigational agent; it is not an approved medicine in the United States or elsewhere, and this page describes only what published studies reported. This page is for educational purposes only and is not medical advice; consult a licensed physician about any medical question.

What class of molecule is it, and where does it come from?

Rencofilstat belongs to the cyclophilin inhibitor class. Cyclophilins are peptidyl-prolyl isomerases — enzymes that catalyse cis–trans isomerisation of proline bonds and act as chaperones in protein folding, immune signalling, mitochondrial permeability regulation, collagen processing and the replication of several viruses. Inhibiting them alters multiple downstream pathways at once, which is why the class has been explored across fibrosis, viral hepatitis and cancer biology.

Structurally, rencofilstat sits in the same family as cyclosporine A, which is itself a cyclic undecapeptide produced by a fungus. Rencofilstat is a synthetic, chemically modified analogue of that scaffold. For that reason it is often described as peptide-derived or as a macrocyclic peptidomimetic rather than as a conventional linear research peptide such as BPC-157 or a GLP-1 analogue. Unlike most injectable research peptides, rencofilstat has been evaluated as an oral agent, and a published human pharmacokinetic study specifically examined how a high-fat meal affected single-dose oral bioavailability in healthy human subjects (PMID 36251165).

How the term is used in the research literature

In papers and conference material the name appears in three consistent ways:

• As a compound name. "Rencofilstat" and the earlier code "CRV431" refer to the same molecule; older publications and preclinical work more often use CRV431.
• As a class exemplar. Authors frequently write "the cyclophilin inhibitor rencofilstat" to signal mechanism rather than to describe a specific product, as in the title of the hepatocellular carcinoma work (PMID 37896876).
• As an investigational comparator. In combination experiments it is paired with other agents to test whether cyclophilin inhibition adds to an existing mechanism, as in work combining it with the proteasome inhibitor ixazomib in prostate cancer cells (PMID 41153724).

Because it is not a growth-factor or hormone analogue, rencofilstat does not overlap with the metabolic or regenerative peptide categories that dominate consumer peptide discussion. Its appearance in peptide glossaries reflects its cyclosporine-derived macrocyclic origin and its mechanism at a protein-folding enzyme.

What the published literature reports

Liver disease: NASH/MASH with fibrosis

The clearest human data come from liver research. Researchers published a phase 2a, multicenter, single-blind, placebo-controlled study of rencofilstat in adults with F2/F3 NASH, which the authors framed as an evaluation of the cyclophilin inhibitor in a fibrotic liver population (PMID 36271849). A later report in Liver International described rencofilstat treatment as improving liver function in MASH with advanced fibrosis when quantified using the HepQuant DuO test, a dual-cholate method of measuring hepatic function and portal circulation (PMID 39982177). Both publications are the primary sources for any statement about rencofilstat in human liver disease; readers evaluating the compound are directed to the original abstracts for endpoint definitions, participant numbers and the magnitude of any changes reported.

Hepatitis C and liver cancer models

Cyclophilin A participates in hepatitis C virus (HCV) replication, so the class has a long history in virology. In a 2023 study, the researchers reported that rencofilstat decreased HCV-induced hepatocellular carcinoma independently of its antiviral activity, separating the anti-tumour observation from viral suppression (PMID 37896876). The same work was first posted as a preprint describing the same independence of antiviral effect (PMID 37645728). That distinction matters for interpretation: the study's framing implies a host-directed mechanism rather than simple viral clearance.

Oncology cell work

Outside the liver, a 2025 Biomedicines paper reported that rencofilstat combined with the proteasome inhibitor ixazomib increased proteotoxic cell death in advanced prostate cancer cells, with the authors describing minimal effects on non-cancer cells in the same experiments (PMID 41153724). This was cell-based laboratory work, not a clinical trial, and the study does not establish clinical benefit in people.

Pharmacokinetics and oral delivery

Because rencofilstat is taken orally, food effects are pharmacologically relevant. The study in Clinical Pharmacology in Drug Development examined the effect of a high-fat meal on single-dose rencofilstat (CRV431) oral bioavailability in healthy human subjects (PMID 36251165). Food-effect studies of this kind are standard in drug development and inform how later trials are designed; they are not instructions for individuals.

Published studies at a glance

Safety and Tolerability: What Studies Report

Tolerability information for rencofilstat comes from its human studies rather than from case reports. The phase 2a NASH publication was designed as a single-blind, placebo-controlled trial, a structure that allows adverse events in treated participants to be compared against placebo (PMID 36271849), and the food-effect study was conducted in healthy human subjects receiving a single oral dose (PMID 36251165). Event-level detail, laboratory findings and discontinuation data are contained in those source publications and are not reproduced or summarised numerically here. Preclinical and cell-culture findings — including the observation of minimal effects on non-cancer cells in prostate cancer experiments (PMID 41153724) — do not describe human safety.

Status and common points of confusion

• Not an approved drug. Rencofilstat is investigational. No regulator has approved it for any indication, and it is not available as a prescription medicine.
• Not a typical research peptide. It is an oral macrocycle derived from a cyclic peptide scaffold, not an injectable peptide analogue.
• CRV431 is the same molecule. The two names appear interchangeably in the literature, with CRV431 used in earlier publications (PMID 36251165).
• NASH and MASH refer to the same disease. Nomenclature changed during the period these studies were published, which is why both terms appear across the cited papers.

This entry is definitional. It does not describe dosing, administration, sourcing or any protocol, and nothing here should be interpreted as a suggestion to use rencofilstat. Anyone with questions about liver disease or investigational therapies is directed to a licensed physician.

References

• Rencofilstat, a cyclophilin inhibitor: A phase 2a, multicenter, single-blind, placebo-controlled study in F2/F3 NASH (Hepatology Communications, 2022)
• Effect of a High-Fat Meal on Single-Dose Rencofilstat (CRV431) Oral Bioavailability in Healthy Human Subjects (Clinical Pharmacology in Drug Development, 2023)
• The Cyclophilin Inhibitor Rencofilstat Decreases HCV-Induced Hepatocellular Carcinoma Independently of Its Antiviral Activity (Viruses, 2023)
• The Cyclophilin Inhibitor Rencofilstat Decreases HCV-induced Hepatocellular Carcinoma Independently of Its Antiviral Activity (bioRxiv, 2023)
• Rencofilstat Treatment Improves Liver Function in MASH With Advanced Fibrosis as Quantified by HepQuant DuO (Liver International, 2025)
• Cyclophilin Inhibitor Rencofilstat Combined with Proteasome Inhibitor Ixazomib Increases Proteotoxic Cell Death in Advanced Prostate Cancer Cells with Minimal Effects on Non-Cancer Cells (Biomedicines, 2025)