JBI-1044 / Jubilant Pharmova - LARVOL DELTA

Peptidylarginine deiminase 4-mediated citrullination in human disease: molecular mechanisms and therapeutic targeting. (PubMed, Front Pharmacol) - "Drug development has progressed from early irreversible inhibitors, including Cl-amidine and F-amidine, to more selective reversible compounds such as GSK484 and GSK199, as well as newer orally available candidates such as JBI-589 and JBI-1044. Emerging approaches, including allosteric ligands, cyclic peptides, and functional antibodies, continue to broaden the PAD4-targeting landscape. In this review, we summarize the molecular basis of PAD4-mediated citrullination, examine its contributions to major disease settings, evaluate current and emerging PAD4-directed therapies, and discuss the key challenges that must be addressed for successful clinical translation."

Journal • Review • Atherosclerosis • Cardiovascular • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Oncology • Rheumatoid Arthritis • Rheumatology • Septic Shock • Systemic Lupus Erythematosus • Thrombosis

Chronic alcohol consumption promotes pancreatic cancer liver metastasis in mice through PAD4-mediated pre-metastatic niche formation (AACR 2025) - "By regulating neutrophil activity and collagen deposition, PAD4 contributes to the progression of liver metastases. Selective inhibition of PAD4 with JBI-1044 represents a promising therapeutic strategy for managing PDAC liver metastasis in the context of ALD."

Metastases • Preclinical • Liver Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • VIM

A patent review of peptidylarginine deiminase 4 (PAD4) inhibitors (2014-present). (PubMed, Expert Opin Ther Pat) - "Despite PAD4's clear involvement in multiple disease pathways, its detailed mechanism remains insufficiently understood. Selective and potent compounds with improved PK properties have been provided but most research on PAD4 is still at the experimental stage or preclinical development; the most promising is JBI-1044, at the IND stage, while some companies have turned to antibodies despite considerable previous investment in small molecules."

Journal • Review • Cardiovascular • CNS Disorders • Immunology • Oncology

SELECTIVE PAD4 INHIBITION DELAYS METASTATIC TUMOR GROWTH IN THE LIVER BY MODULATING THE HEPATIC TUMOR MICROENVIRONMENT (AASLD 2023) - "PAD4 expression is associated with the progression of PDAC and CRC liver metastasis. PAD4 plays pivotal roles in reshaping liver tumor microenvironment through the modulation of neutrophil functions and collagen deposition. PAD4 inhibition by JBI-1044 suppressed liver metastasis, providing new insight of potential therapies targeting PAD4 in PDAC and CRC liver metastasis."

Biomarker • Metastases • Tumor microenvironment • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Liver Failure • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Jubilant Therapeutics Inc. to Present Data on Isoform Selective PAD4 inhibitors in the Treatment of Cancer at the American Association of Cancer Research Annual (AACR) Meeting 2022 (PRNewswire) - "Jubilant Therapeutics Inc...announced...that it will present data on inhibitors of peptidyl arginine deiminase type-4 (PAD4), a potential therapeutic target to treat cancer and autoimmune diseases. The meeting will be held at the American Association of Cancer Research Annual (AACR) in New Orleans between April 8 to 13, 2022, both in person and virtually."

Preclinical • Oncology