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Last update 08 May 2025

REG3A

Last update 08 May 2025

Basic Info

Synonyms

Hepatointestinal pancreatic protein, HIP, HIP/PAP

+ [17]

Introduction

Bactericidal C-type lectin which acts exclusively against Gram-positive bacteria and mediates bacterial killing by binding to surface-exposed carbohydrate moieties of peptidoglycan (PubMed:16931762). Binds membrane phospholipids and kills bacteria by forming a hexameric membrane-permeabilizing oligomeric pore (PubMed:24256734). Acts as a hormone in response to different stimuli like anti-inflammatory signals, such as IL17A, or gut microbiome. Secreted by different cell types to activate its receptor EXTL3 and induce cell specific signaling pathways (PubMed:19158046, PubMed:22727489, PubMed:27830702, PubMed:34099862). Induced by IL17A in keratinocytes, regulates keratinocyte proliferation and differentiation after skin injury via activation of EXTL3-PI3K-AKT signaling pathway (PubMed:22727489). In parallel, inhibits skin inflammation through the inhibition of inflammatory cytokines such as IL6 and TNF (PubMed:27830702). In pancreas, is able to permealize beta-cells membrane and stimulate their proliferation (PubMed:19158046). Has bacteriostatic activity.

Drugs associated with REG3A

Recombinant hepatocarcinoma-intestine-pancreas pancreatitis-associated protein(INSERM)

Target

REG3A

Mechanism

REG3A modulators

Active Org.-

Originator Org.

Atos SE

Active Indication-

Inactive Indication

Acute hepatitis [+7]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with REG3A

EUCTR2010-020657-14-DE

/ Not yet recruitingNot Applicable

A multicentre, double-blind, randomized, placebo-controlled study to evaluate the efficacy and the safety of ALF-5755 in patients with nonacetaminophen severe acute hepatitis and early stage acute liver failure

Start Date04 Jul 2011

Sponsor / Collaborator

Alfact Innovation SAS

NCT01318525

/ Unknown statusPhase 2

A Multicentre, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and the Safety of ALF-5755 in Patients With Nonacetaminophen Severe Acute Hepatitis and Early Stage Acute Liver Failure

Acute liver failure is a rare but dramatic disease, often affecting young people, marked by the sudden loss of liver function in a person without preexisting liver disease.
ALF-5755 has been shown to promote cell survival after apoptotic or oxidative stress, and liver cell regeneration in primary cultures and in vivo. ALF-5755 may become, in this dramatic disease with high unmet medical need, a future therapy for the treatment of patients suffering from severe acute hepatitis (SAH) and acute liver failure (ALF) not due to acetaminophen overdose, where liver transplantation is the sole treatment in the absence of spontaneous recovery.
The primary objective of the study is to evaluate the efficacy of ALF-5755 versus placebo.
A minimum of 60 patients will be recruited into the study in the following two treatment groups:
Group A: approximately 30 patients will receive ALF-5755
Group B: approximately 30 patients will receive placebo (physiological saline solution: 0.9% NaCl)
Patients will receive 10 mg (25 ml) of ALF5755 or placebo every 12 hours over 3 days in slow intravenous infusions over 10 minutes using automatic syringes.

Start Date01 Oct 2010

Sponsor / Collaborator

Alfact Innovation SAS

100 Clinical Results associated with REG3A

100 Translational Medicine associated with REG3A

0 Patents (Medical) associated with REG3A

242

Literatures (Medical) associated with REG3A

01 May 2025·Hepatology

Tumor suppressive role of the antimicrobial lectin REG3A targeting the O-GlcNAc glycosylation pathway

Article

Author: R Vivès, Romain ; Darnaud, Marion ; Geoffre, Nicolas ; Deshayes, Alice ; Lacoste, Claire ; Bréchot, Christian ; Purhonen, Janne ; Moniaux, Nicolas ; Amouyal, Paul ; Amouyal, Gilles ; Buendia, Marie Annick ; Friedel-Arboleas, Mélanie ; Faivre, Jamila ; Guettier, Catherine ; Nguyen, Tung-Son ; Dos Santos, Alexandre ; Kallijärvi, Jukka ; Job, Sylvie ; Issad, Tarik ; Vivès, Romain R.

Background and Aims:Antimicrobial proteins of the regenerating family member 3 alpha (REG3A) family provide a first line of protection against infections and transformed cells. Their expression is inducible by inflammation, which makes their role in cancer biology less clear since an immune-inflammatory context may preexist or coexist with cancer, as occurs in HCC. The aim of this study is to clarify the role of REG3A in liver carcinogenesis and to determine whether its carbohydrate-binding functions are involved.Approach and Results:This study provides evidence for a suppressive role of REG3A in HCC by reducing O-GlcNAcylation in 2 mouse models of HCC, in vitro cell studies, and clinical samples. REG3A expression in hepatocytes significantly reduced global O-GlcNAcylation and O-GlcNAcylation of c-MYC in preneoplastic and tumor livers and markedly inhibited HCC development in REG3A-c-MYC double transgenic mice and mice exposed to diethylnitrosamine. REG3A modified O-GlcNAcylation without altering the expression or activity of O-linked N-acetylglucosaminyltransferase, O-linked N-acetylglucosaminyl hydrolase, or glutamine fructose-6-phosphate amidotransferase. Reduced O-GlcNAcylation was consistent with decreased levels of UDP-GlcNAc in precancerous and cancerous livers. This effect was linked to the ability of REG3A to bind glucose and glucose-6 phosphate, suggested by a REG3A mutant unable to bind glucose and glucose-6 phosphate and alter O-GlcNAcylation. Importantly, patients with cirrhosis with high hepatic REG3A expression had lower levels of O-GlcNAcylation and longer cancer-free survival than REG3A-negative cirrhotic livers.Conclusions:REG3A helps fight liver cancer by reducing O-GlcNAcylation. This study suggests a new paradigm for the regulation of O-GlcNAc signaling in cancer-related pathways through interactions with the carbohydrate-binding function of REG3A.

01 Mar 2025·Cancer Letters

Lead time trajectory of blood-based protein biomarkers for detection of pancreatic cancer based on repeat testing

Article

Author: Schmidt, C Max ; Yip-Schneider, Michele ; Long, James P ; Zhang, Jianjun ; Fahrmann, Johannes F ; Maitra, Anirban ; Vykoukal, Jody ; Hanash, Samir ; Do, Kim-Anh ; Spencer, Rachelle ; Irajizad, Ehsan ; Dennison, Jennifer B

In the current study, we assessed whether repeated measurements of a panel of protein biomarkers with relevance to pancreatic ductal adenocarcinoma (PDAC) improves lead time performance for earlier detection over a single timepoint measurement. Specifically, CA125, CEA, LRG1, REG3A, THBS2, TIMP1, TNRFSF1A as well as CA19-9 were assayed in serially collected pre-diagnostic plasma from 242 PDAC cases and 242 age- and sex-matched non-case control participants in the PLCO cohort. We compared performance estimates of a parametric empirical Bayes (PEB) algorithm, which incorporates participant biomarker history, to that of a single-threshold (ST) method. We demonstrated improvements in AUC estimates (2-13 %) for all biomarkers when considering the PEB approach compared to ST. For CA19-9, the PEB^CA19-9 yielded an AUC of 0.88 when at least one repeat measurement was within 3 years of clinical diagnosis. At a specificity of 98.5 %, the PEB^CA19-9 identified 15 of the 41 PDAC cases and signaled positive at an average lead-time of 1.09 years whereas the ST approach captured 11 of the 41 PDAC cases with an average positive signal at 0.48 years. Among CA19-9 low individuals, a PEB algorithm based on repeat measurements of TIMP1 yielded an additional 14 % sensitivity at 98.5 % specificity. An adaptive algorithm that considers repeated CA19-9 measurements improves sensitivity and lead-time detection of PDAC compared to a single-threshold method. Additional protein biomarkers may improve sensitivity for earlier detection of PDAC among cases with low CA19-9.

01 Dec 2024·Clinical Gastroenterology and Hepatology

A Randomized Phase II Study of Efmarodocokin Alfa, an interleukin-22 Agonist, Versus Vedolizumab in Patients With Ulcerative Colitis

Article

Author: Peyrin-Biroulet, Laurent ; Chen, Yiling ; Rothenberg, Michael E ; Lim, Jeremy J ; McBride, Jacqueline M ; Keir, Mary ; Danese, Silvio ; Dash, Ajit ; Mar, Jordan S ; Ding, Han Ting ; Colombel, Jean-Frederic ; Panes, Julian ; Feagan, Brian ; Schreiber, Stefan ; Valentine, John F

BACKGROUND & AIMSEfmarodocokin alfa is an interleukin (IL)-22 agonist, with favorable pharmacokinetic properties and an acceptable safety profile. This study further explored the therapeutic potential of efmarodocokin alfa compared with vedolizumab in patients with ulcerative colitis (UC).METHODSThis randomized phase II trial evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of 3 doses of efmarodocokin alfa administered intravenously every 4 weeks (30 μg/kg [n = 43], 60 μg/kg [n = 44], and 90 μg/kg [n = 43]) compared with placebo (n = 22) and with vedolizumab (n = 43) in the treatment of moderate to severe UC. Key clinical outcomes were assessed through the modified Mayo Clinic Score, and endoscopic evaluations by a central reader.RESULTSEfmarodocokin alfa was adequately tolerated with an acceptable safety profile. Although efmarodocokin alfa did not show statistically significant improvement in clinical remission, clinical response, endoscopic healing, or endoscopic remission at week 8 compared with placebo, vedolizumab demonstrated some efficacy. Clinical remission was achieved by 12%, 9%, and 12% of patients in the 30, 60, and 90 μg/kg dose arms, respectively, compared with 9% and 26% of patients in the placebo and vedolizumab arms at week 8. Similarly, endoscopic healing at week 8 was achieved by 14%, 14%, and 12% of patients in the 30, 60, and 90 μg/kg dose arms, respectively, compared with 14% and 33% of patients in the placebo and vedolizumab arms. A dose-dependent increase in pharmacodynamic biomarkers was observed (regenerating islet-derived protein 3-alpha and C-reactive protein levels).CONCLUSIONEfmarodocokin alfa did not demonstrate efficacy compared with placebo, and this phase II study was ended early for futility; however, there was evidence of target engagement (skin adverse events, regenerating islet-derived protein 3-alpha levels).CLINICALTRIALSgov, Number: NCT03558152.

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