467426-54-6

Plecanatide is used in the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. It works as a laxative by drawing water in to the gastrointestinal tract thereby softening stool and encouraging its natural passage.

This uroguanylin analogue (FW = 1681.90 g/mol; CAS 467426-54-6), also known by the codename SP-304, binds to and activates guanylate cyclase-C (GC-C) receptors (EC50 ≈ 0.3 μM) expressed on the epithelial cells lining the gastrointestinal mucosa, stimulating cyclic GMP production, which in turn sequentially activates protein kinase G-II and the chloride channel known as the Cystic Fibrosis Transmembrane-conductance Regulator (CFTR) to regulate ion and fluid transport, to promote epithelial cell homeostasis, and to maintain barrier function in the GI mucosa. Plecanatide is a hexadecapeptide that is structurally identical to uroguanylin, except for an glutamate substitution at position-3. Oral treatment with plecanatide at a dose range between 0.05-2.5 mg/kg per day is as effective as once-daily treatment with 5-amino salicylic acid (100 mg/kg) or sulfasalazine (80 mg/kg). Amelioration of colitis by the treatment with plecanatide or dolcanatide was not dose-dependent, most likely due to saturation of available GC-C receptors.