Calhex 231

Calhex 231 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 can be used in the study of traumatic hemorrhagic shock (THS) and diabetic cardiomyopathy (DCM)^[1]. IC50 & Target:CaSR^[1]
IC50: 0.39 μM (Inositol phosphate)^[1] 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].
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].