A novel chemoreactive calcilytic for the potential treatment of autosomal dominant hypocalcemia.

ABSTRACT: Autosomal dominant hypocalcemia (ADH) type 1 and 2 are disorders of calcium homeostasis caused by gain of function variants. The calcium-sensing receptor (CaSR) is a class C GPCR that responds to elevated extracellular calcium (Ca²⁺ _o) by inhibiting parathyroid hormone (PTH) secretion and promoting renal excretion of Ca²⁺ and other salts to restore physiologically normal Ca²⁺ _o concentrations. CaSR negative allosteric modulators (NAMs) transiently raise PTH levels in individuals with ADH1, restoring Ca²⁺ _o concentration to a physiological normal range. Herein we disclose the discovery of a chemoreactive NAM (ATF936-NCS, 4) for the CaSR that (i) is wash-resistant indicative of irreversible receptor binding a

SUBMITTER: Dangerfield J 

PROVIDER: S-EPMC12541615 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature