RBN-3143

RBN-3143 is a first-in-class, orally administered small molecule inhibitor of poly(ADP-ribose) polymerase 14 (PARP14), developed by Ribon Therapeutics for the treatment of inflammatory diseases. PARP14 is a NAD+-utilizing mono-ADP-ribosyltransferase that regulates cell signaling and protein function, with elevated expression in tissues affected by inflammatory conditions such as atopic dermatitis, asthma, and ulcerative colitis. By selectively inhibiting PARP14—over 300-fold selectivity compared to other PARPs—RBN-3143 suppresses disease markers in preclinical models of lung, skin, and gastrointestinal inflammation. Mechanistically, inhibition of PARP14 reduces Th2/Th17 cytokine signaling (including IL-4/13 and IL-17 pathways), leading to decreased eosinophil and neutrophil infiltration in inflamed tissues. Clinical studies have shown favorable safety and pharmacokinetic profiles in healthy volunteers; the drug is currently being evaluated for moderate-to-severe atopic dermatitis[1][2][3][4][5][6].