| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Calcium-sensing receptor (CaSR) (negative allosteric modulator, NAM). Blocks CaSR activation without competing with calcium. IC50 = 0.39 microM for blocking increases in [3H]inositol phosphate (IP) elicited by activation of human wild-type CaSR in transiently transfected HEK293 cells.
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| ln Vitro |
Treatment with Calhex 231 dramatically lowers the proliferation of cardiac fibroblasts [1]. Treatment with Calhex 231 markedly reduced the expression of MMP2/9, Col-I/III, α-SMA, and CaSR. In cardiac fibroblasts, calhex231 attenuates high glucose-induced heart fibrosis [1]. Calhex 231 has the ability to suppress the Itch (atropin-1 interacting protein 4)-ubiquitin proteasome and TGF-β1/Smads pathways. This means that it can lessen the effects of glucose-induced myocardial fibrosis, reduce collagen deposition, and stop the growth of cardiac fibroblasts [1].
Dose-dependently inhibits IP response induced by 10 mM Ca2+ with IC50 = 0.39 microM in WT CaSR; potency similar in T764A (0.28 microM) and H766A (0.64 microM) mutant receptors. Downregulates CaSR, alpha-SMA, Col-I/III, MMP2/9 expression; inhibits Itch-ubiquitin proteasome and TGF-beta1/Smads pathways; suppresses cardiac fibroblast proliferation and collagen deposition. |
| ln Vivo |
In type 1 diabetes model (T1D) rats, intraperitoneal injection of Calhex 231 (4.07 mg/kg (10 µmol/kg) given daily for 12 weeks; male Wistar rats) ameliorates diabetic myocardium fibrosis [1].
Ameliorates diabetic myocardial fibrosis in type 1 diabetic (T1D) rats at 4.07 mg/kg (10 umol/kg; IP; daily for 12 weeks). Mitigates traumatic hemorrhagic shock (THS) at 0.1-1 mg/kg, improving vascular hyporesponsiveness and reducing mitochondrial dysfunction. Calhex 231 (dose range 0.1-10 mg/kg) shows protective effects in multiple in vivo models. |
| Enzyme Assay |
Not applicable. CaSR is a GPCR, not an enzyme. [3H]Inositol phosphate (IP) accumulation assay: HEK293 cells transiently transfected with human wild-type CaSR (or mutant variants) are labeled with myo-[3H]inositol (overnight). Cells are incubated with Calhex 231 (0.001-100 uM) for 15 min, then stimulated with 10 mM Ca2+ (agonist) for 30 min. Total [3H]IP is extracted by anion exchange chromatography (Dowex AG1-X8 resin) and quantified by liquid scintillation counting. IC50 calculated from inhibition of Ca2+-induced IP accumulation.
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| Cell Assay |
Cell proliferation assay[1]
Cell Types: Primary neonatal rat cardiac fibroblasts (CF) Tested Concentrations: 3 µM Incubation Duration: 24 hrs (hours) Experimental Results: Dramatically diminished cardiac fibroblast proliferation. Western Blot Analysis [1] Cell Types: primary neonatal rat cardiac fibroblasts (CFs) Tested Concentrations: 3 µM Incubation Duration: 48 hrs (hours) Experimental Results: CaSR, α-SMA, Col-I/III, and MMP2/9 were Dramatically expressed Downregulation. [3H]IP accumulation assay (as described above) is the primary in vitro assay. For cardiac fibroblasts: Primary rat cardiac fibroblasts are stimulated with high glucose (e.g., 25 mM) to induce fibrosis; Calhex 231 (0.1-10 uM) is added for 24-72h. Myocardial fibrosis markers (alpha-SMA, Col-I, Col-III, MMP2/9) measured by Western blot or qPCR; fibroblast proliferation by BrdU incorporation. |
| Animal Protocol |
Animal/Disease Models: Male Wistar rats (8 weeks old) injected with streptozotocin [1]
Doses: 4.07 mg/kg (10 µmol/kg) Route of Administration: intraperitoneal (ip) injection; daily; continued for 12 weeks Experimental Results: Type 1 Diabetic myocardial fibrosis is improved in diabetic rats. Diabetic cardiomyopathy (DCM) model: Male Wistar rats made diabetic with streptozotocin (STZ, 55 mg/kg IV) to induce type 1 diabetes (T1D). Calhex 231 HCl (4.07 mg/kg = 10 umol/kg; IP) administered once daily for 12 weeks starting 4 weeks post-STZ. Cardiac function assessed by echocardiography (ejection fraction, fractional shortening). Myocardial fibrosis evaluated by Masson‘s trichrome staining and collagen content (hydroxyproline); protein expression (CaSR, alpha-SMA, Col-I, Col-III, MMP2/9) by Western blot. Traumatic hemorrhagic shock (THS) model: Rats subjected to THS (pressure-controlled hemorrhage followed by resuscitation). Calhex 231 (0.1-1 mg/kg; IV or IP) administered before or after resuscitation; endpoints include vascular reactivity, mitochondrial function, tissue edema, and survival. |
| ADME/Pharmacokinetics |
Dedicated PK data for Calhex 231 HCl are not detailed in standard references. As a small molecule NAM (MW 443.41, ClogP ~5.5), it is predicted to have moderate oral bioavailability, high plasma protein binding, and a terminal half-life of several hours. IP administration (4.07 mg/kg) achieves adequate exposure for once-daily dosing in rats.
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| Toxicity/Toxicokinetics |
Very toxic to aquatic life with long lasting effects (H410). Not a hazardous substance or mixture under normal handling (MSDS for similar material). Under fire conditions, may decompose and emit toxic fumes. Standard laboratory precautions should be followed: P264 Wash skin thoroughly after handling; P270 Do not eat, drink or smoke when using this product. Aquatic toxicity is a concern; avoid environmental release.
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| References |
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| Additional Infomation |
Calhex 231 (also known as NPS 2143 analog) was originally developed as a negative allosteric modulator of CaSR. The hydrochloride salt improves solubility and handling. The compound is a valuable tool for studying CaSR-mediated signaling in calcium homeostasis, bone remodeling, and cardiovascular fibrosis. It enhances PTH release (via CaSR inhibition in the parathyroid gland), making it useful for studying calcium metabolism. Potential therapeutic applications include diabetic cardiomyopathy (DCM), traumatic hemorrhagic shock (THS), and asthma. Not FDA-approved; for research use only. Adverse effects in animals are not detailed; the compound appears well-tolerated at the tested doses (0.1-10 mg/kg range) in rodent models. The NAM mechanism distinguishes Calhex 231 from competitive antagonists (calcilytics) that bind the orthosteric site.
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| Molecular Formula |
C25H28CL2N2O
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|---|---|
| Molecular Weight |
443.4086
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| Exact Mass |
442.157
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| CAS # |
2387505-78-2
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| Related CAS # |
(1R,2R)-Calhex 231 hydrochloride
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| PubChem CID |
11849513
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
533
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| Defined Atom Stereocenter Count |
3
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| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1[H])C(N([H])[C@@]1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[C@]1([H])N([H])[C@]([H])(C([H])([H])[H])C1=C([H])C([H])=C([H])C2=C([H])C([H])=C([H])C([H])=C12)=O.Cl[H]
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| InChi Key |
KZPHZSFSFANQIS-GRFVZBLOSA-N
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| InChi Code |
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
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| Chemical Name |
4-chloro-N-[(1S,2S)-2-[[(1R)-1-naphthalen-1-ylethyl]amino]cyclohexyl]benzamide;hydrochloride
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| Synonyms |
Calhex231 HCl; Calhex-231 HCl
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~33.33 mg/mL (~75.17 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.64 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2552 mL | 11.2762 mL | 22.5525 mL | |
| 5 mM | 0.4510 mL | 2.2552 mL | 4.5105 mL | |
| 10 mM | 0.2255 mL | 1.1276 mL | 2.2552 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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