Calhex 231 hydrochloride

Calhex 231 hydrochloride is a CaSR inhibitor via negative allosteric modulation. Calhex 231 hydrochloride blocks Ca2+-induced accumulation of [3H]inositol phosphate with an IC50 of 0.39 μM in HEK293 cells. Calhex 231 hydrochloride has the potential for diabetic cardiomyopathy (DCM) treatment[1][2].

Research Areas >> Metabolic Disease

Signaling Pathways >> GPCR/G Protein >> CaSR

CaSR[1] IC50: 0.39 μM (Inositol phosphate)[2]

Calhex 231 treatment significantly decreases the proliferation of cardiac fibroblasts[1]. Calhex 231 treatment significantly downregulates the CaSR, α-SMA, Col-I/III, MMP2/9 expresses. Calhex231 alleviates high glucose-induced myocardial fibrosis in cardiac fibroblasts[1]. Calhex 231 could inhibit Itch (atrophin-1 interacting protein 4)-ubiquitin proteasome and TGF-β1/Smads pathways, and then depress the proliferation of cardiac fibroblasts, along with the reduction deposition of collagen, alleviate glucose-induced myocardial fibrosis[1]. Cell Proliferation Assay[1] Cell Line: Primary neonatal rat cardiac fibroblasts (CFs) Concentration: 3 µM Incubation Time: 24 hours Result: Significantly decreased the proliferation of cardiac fibroblasts. Western Blot Analysis[1] Cell Line: Primary neonatal rat cardiac fibroblasts (CFs) Concentration: 3 µM Incubation Time: 48 hours Result: The expression of CaSR, α-SMA, Col-I/III, MMP2/9 were significantly downregulated.

Calhex 231 (4.07 mg/kg (10 µmol/kg); intraperitoneal injection; daily; for 12 weeks; male Wistar rats) treatment ameliorates diabetic myocardial fibrosis in type 1 diabetic model (T1D) rats[1]. Animal Model: Male Wistar rats (8 weeks old) injected with Streptozotocin[1] Dosage: 4.07 mg/kg (10 µmol/kg) Administration: Intraperitoneal injection; daily; for 12 weeks Result: Ameliorated diabetic myocardial fibrosis in T1D rats.

[1]. Yuan H, et al. Calhex231 Alleviates High Glucose-Induced Myocardial Fibrosis via Inhibiting Itch-Ubiquitin Proteasome Pathway in Vitro. Biol Pharm Bull. 2019 Aug 1;42(8):1337-1344.

[2]. Petrel C1, et al. Modeling and mutagenesis of the binding site of Calhex 231, a novel negative allosteric modulator of the extracellular Ca(2+)-sensing receptor. J Biol Chem. 2003 Dec 5;278(49):49487-94.