Calhex 231 hydrochloride

• CAT Number: I015591
• CAS Number: 2387505-78-2
• Molecular Formula: C25H28Cl2N2O
• Molecular Weight: 443.41
• Purity: ≥95%
• Synonyms: 4-chloro-N-[(1S,2S)-2-[[(1R)-1-naphthalen-1-ylethyl]amino]cyclohexyl]benzamide;hydrochloride
• InChI: InChI=1S/C25H27ClN2O.ClH/c1-17(21-10-6-8-18-7-2-3-9-22(18)21)27-23-11-4-5-12-24(23)28-25(29)19-13-15-20(26)16-14-19;/h2-3,6-10,13-17,23-24,27H,4-5,11-12H2,1H3,(H,28,29);1H/t17-,23+,24+;/m1./s1
• InChIKey: KZPHZSFSFANQIS-GRFVZBLOSA-N
• SMILES: CC(C1=CC=CC2=CC=CC=C21)NC3CCCCC3NC(=O)C4=CC=C(C=C4)Cl.Cl

Calhex 231 hydrochloride is a potent negative allosteric modulator that blocks (IC50 = 0.39 μM) increases in [3H]inositol phosphates elicited by activating the human wild-type CaSR transiently Ca2+-sensing receptor. Calhex 231 hydrochloride can be used in the study of traumatic hemorrhagic shock (THS) and diabetic cardiomyopathy (DCM)[1].
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].
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].

Reference

[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.
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[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.
 [Content Brief]

[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.
 [Content Brief]