Undisclosed PAD inhibitor / BMS, Evotec - LARVOL DELTA

Crystal structure of human peptidylarginine deiminase type VI (PAD6) provides insights into its inactivity. (PubMed, IUCrJ) - "This observation is further supported by the lack of activity on the histone H3 and cytokeratin 5 substrates. These findings suggest a different mechanism for enzymatic activation compared with other PADs; alternatively, PAD6 may exert a non-enzymatic function in the cytoplasmic lattice of oocytes and early embryos."

Journal • KRT5

Detection of Citrullinated Proteins Recognized by a Novel Chimeric Antigen Receptor TregTherapy in Both Synovial Fluid and Serum from Patients with Rheumatoid Arthritis (ACR Convergence 2023) - "Protein citrullination is a post-translational modification in which arginine is converted to citrulline through a process mediated by the activity of peptidylarginine deiminase enzymes... In summary, we were able to detect CAR-reactive citrullinated antigens for SBT777101 in synovial fluid and serum and these levels correlated with ability to activate the CAR in a cell-based assay, and with several inflammatory markers both in synovial fluid and serum. The presence of these CAR-reactive citrullinated antigens and inflammatory markers will be further evaluated in an upcoming planned phase 1 study. S."

Clinical • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CCL3 • IL6 • TNFA

Anti-Citrullinated Protein Antibody Reactivity towards Neutrophil-Derived Antigens: Clonal Diversity and Inter-Individual Variation. (PubMed, Biomolecules) - "Neutrophils can be important sources of citrullinated antigens under conditions that lead to PAD4 activation, NETosis and the extrusion of intracellular material. A substantial clonal diversity in targeting neutrophils and a high variability among individuals in neutrophil binding and osteoclast stimulation suggest that ACPAs may influence RA-related symptoms with high patient-to-patient variability."

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CXCL8

A novel peptidylarginine deiminase 4 (PAD4) inhibitor BMS-P5 blocks formation of neutrophil extracellular traps and delays progression of multiple myeloma. (PubMed, Mol Cancer Ther) - "Administration of BMS-P5 to MM-bearing mice delays appearance of symptoms and disease progression. Taken together, our data demonstrate that targeting PAD4 may be beneficial for treatment of MM."

Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology