PTH-IA

PTH-IA is a 30-amino acid peptide inverse agonist of the parathyroid hormone 1 receptor (PTH1R). It is specifically designed to treat Jansen's Metaphyseal Chondrodysplasia (JMC), an ultra-rare genetic disorder caused by constitutive activation of PTH1R due to specific mutations (such as H223R, T410P, and I458R). Unlike traditional antagonists that merely block ligand-induced activation, PTH-IA acts as an inverse agonist, meaning it actively suppresses the high basal, ligand-independent cAMP signaling characteristic of the mutant receptors. The peptide is a modified fragment of parathyroid hormone-related protein (PTHrP), specifically the (7-36) sequence with four amino acid substitutions. Developed through a collaboration involving the National Institute of Dental and Craniofacial Research (NIDCR) and researchers at Massachusetts General Hospital, PTH-IA aims to normalize mineral-ion abnormalities (hypercalcemia and hypercalciuria) and mitigate the severe skeletal deformities and kidney damage associated with JMC.

Other names

[Leu11,dTrp12,Trp23,Tyr36]-PTHrP(7-36)NH2parathyroid hormone inverse agonist