Plecanatide

A peptide agonist of the guanylate cyclase C receptor

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5mg

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Background

Plecanatide is a peptide agonist of the guanylate cyclase C receptor.¹ It stimulates cGMP production in T84 colon cancer cells (EC₅₀ = 170 nM). Plecanatide (10 ppm in the diet) reduces increases in the number of neoplastic colon epithelial cells expressing Ki-67, a marker of cell proliferation, induced by dextran sulfate in cancer-prone Apc^+/Min-FCCC mice.² It suppresses trinitrobenzenesulfonic acid-induced increases in abdominal contractions in a rat model of visceral hypersensitivity when administered at doses of 0.01 and 0.05 mg/kg.³ Formulations containing plecanatide have been used in the treatment of chronic idiopathic constipation.

1.Shailubhai, K., Palejwala, V., Arjunan, K.P., et al.Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitisWorld J. Gastrointest. Pharmacol. Ther.6(4)213-222(2015) 2.Chang, W.-C.L., Masih, S., Thadi, A., et al.Plecanatide-mediated activation of guanylate cyclase-C suppresses inflammation-induced colorectal carcinogenesis in Apc+/Min-FCCC miceWorld J. Gastrointest. Pharmacol. Ther.8(1)47-59(2017) 3.Boulete, I.-M., Thai, A., Beaufrand, C., et al.Oral treatment with plecanatide or dolcanatide attenuates visceral hypersensitivity via activation of guanylate cyclase-C in rat modelsWorld J. Gastroenterol.24(17)1888-1900(2018)