lorpucitinib

Lorpucitinib (JNJ-64251330) is an oral, small molecule, gut-restricted pan-Janus kinase (JAK) inhibitor developed for the treatment of inflammatory diseases of the intestinal tract, particularly familial adenomatous polyposis (FAP). It selectively inhibits JAK1, JAK2, JAK3, and Tyk2 with high potency in colonic tissue while minimizing systemic exposure. Lorpucitinib blocks phosphorylation of Signal Transducer and Activator of Transcription (STAT) proteins in the gut mucosa, leading to reduced STAT-3 activation and decreased levels of serum inflammatory biomarkers such as C-reactive protein. Clinical studies have shown that lorpucitinib achieves much higher concentrations in gut tissues than plasma and is generally safe and well tolerated. However, no clinically significant reduction in polyp burden was observed in FAP patients during trials[2][3][5][6].