PTH inverse agonist peptide

PTH inverse agonist peptide (PTH-IA) is a synthetic 30-amino-acid peptide analog of parathyroid hormone-related protein (PTHrP), specifically [Leu11,dTrp12,Trp23,Tyr36]-PTHrP(7-36)NH2. It is being developed as a targeted therapeutic for Jansen's metaphyseal chondrodysplasia (JMC), an ultra-rare autosomal dominant skeletal disorder caused by heterozygous activating mutations in the parathyroid hormone 1 receptor (PTH1R). PTH-IA acts as an inverse agonist at the PTH1R, suppressing the constitutively active mutant receptor's elevated basal levels of cyclic adenosine monophosphate (cAMP) signaling. This action helps normalize mineral ion homeostasis (reducing hypercalcemia and hypercalciuria) and correct skeletal development defects. The drug is being developed by Massachusetts General Hospital in collaboration with the National Center for Advancing Translational Sciences (NCATS) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and is currently in Phase 1/2 clinical trials.

Other names

[Leu11,dTrp12,Trp23,Tyr36]-PTHrP(7-36)NH2Parathyroid Hormone-Inverse AgonistPTH receptor inverse agonist