Calhex 231 hydrochloride is a potent negative allosteric modulator that blocks (IC50 = 0.39 μM) increases in [ 3 H]inositol phosphates elicited by activating the human wild-type CaSR transiently Ca 2+ -sensing receptor. Calhex 231 hydrochloride can be used in the study of traumatic hemorrhagic shock (THS) and diabetic cardiomyopathy (DCM) [1].
In Vivo, 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[2]. Calhex-231 (Cal, 0.1-1 mg/kg) has a mitigating effect on traumatic hemorrhagic shock by improving vascular hyporesponsiveness and reducing mitochondrial dysfunction[3].
In Vitro, Calhex 231 dose-dependently inhibited the IP response induced by 10 mM Ca2+ with a potency in the T764A (IC50 = 0.28 ± 0.05 μM) and H766A (IC50 = 0.64 ± 0.03 μM) mutant receptors similar to that in the WT receptor[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[2]. 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[2].
References:
[1]. Christophe Petrel, 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.
[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.
[3]. Yan Lei, et al. The Calcilytic Drug Calhex-231 Ameliorates Vascular Hyporesponsiveness in Traumatic Hemorrhagic Shock by Inhibiting Oxidative Stress and miR-208a-Mediated Mitochondrial Fission. Oxid Med Cell Longev. 2020 Dec 3:2020:4132785.
In Vivo, 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[2]. Calhex-231 (Cal, 0.1-1 mg/kg) has a mitigating effect on traumatic hemorrhagic shock by improving vascular hyporesponsiveness and reducing mitochondrial dysfunction[3].
In Vitro, Calhex 231 dose-dependently inhibited the IP response induced by 10 mM Ca2+ with a potency in the T764A (IC50 = 0.28 ± 0.05 μM) and H766A (IC50 = 0.64 ± 0.03 μM) mutant receptors similar to that in the WT receptor[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[2]. 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[2].
References:
[1]. Christophe Petrel, 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.
[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.
[3]. Yan Lei, et al. The Calcilytic Drug Calhex-231 Ameliorates Vascular Hyporesponsiveness in Traumatic Hemorrhagic Shock by Inhibiting Oxidative Stress and miR-208a-Mediated Mitochondrial Fission. Oxid Med Cell Longev. 2020 Dec 3:2020:4132785.