CM-4620
(Synonyms: CM-4620) 目录号 : GC19107
CM-4620是一种选择性Orai通道抑制剂，对Orai1和Orai2的IC50值分别为0.119μM和0.895μM。
Cas No.:1713240-67-5
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
CM-4620 is a selective inhibitor of Orai channels, with IC50 = 0.119μM for Orai1 and 0.895μM for Orai2[1]. CM-4620 could inhibit the activation of the cell death pathway by inhibiting Store-operated Ca2+ entry (SOCE)[2]. CM-4620 has been widely used to alleviate acute pancreatitis in mouse models[3].
In vitro, CM-4620 (2μM) treatment for 72 hours resulted in upregulation of the expression of genes involved in gluconeogenesis, glycolysis, citric acid cycle, carbohydrate metabolism, respiratory electron transport, and endoplasmic reticulum stress within mouse cardiac fibroblasts (CFs), without affecting cell proliferation[4]. Pretreatment of pancreatic acinar cells (PAC) with 1µM CM-4620 for 30min resulted in a significant decrease in Ca2+ influx and prevented palmitic acid-induced cell necrosis[5]. Treatment of Duchenne muscular dystrophy (DMD) patient-derived induced pluripotent stem cells (iPSCs) with 1µM of CM-4620 for one hour inhibited Ca2+ overload and reduced peak Ca2+ levels[6].
In vivo, CM-4620 treatment via continuous intravenous infusion at a dose of 20mg/kg for 4 hours improved cerulein-induced acute pancreatitis and inhibited cell death signaling activation in rats[7]. Intraperitoneal injection of CM-4620 (20mg/kg) every 12 hours for a day reduced systemic inflammatory response in a mouse model of lipopolysaccharide-induced sepsis[8].
References:
[1] Rubaiy H N. ORAI Calcium channels: Regulation, function, pharmacology, and therapeutic targets[J]. Pharmaceuticals, 2023, 16(2): 162.
[2] Liang X, Zhang N, Pan H, et al. Development of store-operated calcium entry-targeted compounds in cancer[J]. Frontiers in pharmacology, 2021, 12: 688244.
[3] Bhardwaj R, Parekh A B. CRAC channels and patho-physiology of peripheral organ systems[J]. Biochemical Society Transactions, 2025: BST20253062.
[4] Pantoja Newman P S, Bajwa A, De Mario A, et al. Orai channel pharmacological manipulation reduces metabolic flexibility in cardiac fibroblasts[J]. American Journal of Physiology-Cell Physiology, 2025, 328(6): C1880-C1892.
[5] Lewis S, Evans D L, Tsugorka T T, et al. Combination of the CRAC channel inhibitor CM4620 and galactose as a potential therapy for acute pancreatitis[J]. Function, 2024, 5(4): zqae017.
[6] Skopin A Y, Glushankova L N, Gusev K O, et al. Vulnerability of Store-Operated Calcium Entry to Inhibitors and Microenvironment in Cells of Different Breast Cancer Subtypes[J]. Life, 2024, 14(3): 357.
[7] Waldron R T, Chen Y, Pham H, et al. The Orai Ca2+ channel inhibitor CM4620 targets both parenchymal and immune cells to reduce inflammation in experimental acute pancreatitis[J]. The Journal of physiology, 2019, 597(12): 3085-3105.
[8] Mei W, Zhang X, Niu M, et al. Deletion of myeloid-specific Orai1 calcium channel does not affect pancreatic tissue damage in experimental acute pancreatitis[J]. Pancreatology, 2024, 24(4): 528-537.
CM-4620是一种选择性Orai通道抑制剂，对Orai1和Orai2的IC50值分别为0.119μM和0.895μM[1]。CM-4620通过抑制Store-operated Ca2+ entry (SOCE)阻断细胞死亡通路的激活[2]。CM-4620已广泛应用于小鼠模型以缓解急性胰腺炎[3]。
在体外，2μM的CM-4620处理小鼠心脏成纤维细胞（CFs）72小时可上调糖异生、糖酵解、柠檬酸循环、碳水化合物代谢、呼吸电子传递及内质网应激相关基因的表达，且不影响细胞增殖[4]。1µM的CM-4620预处理胰腺腺泡细胞（PAC）30分钟能显著降低Ca2+内流并预防棕榈酸诱导的细胞坏死[5]。1µM的CM-4620处理杜氏肌营养不良症（DMD）患者来源的诱导多能干细胞（iPSCs）1小时可抑制Ca2+超载并降低峰值钙离子水平[6]。
在体内，大鼠持续静脉输注CM-4620（20mg/kg；4小时）可改cerulein诱导的急性胰腺炎并抑制细胞死亡信号激活[7]。小鼠每12小时腹腔注射CM-4620（20mg/kg）持续一天能减轻脂多糖诱导的脓毒症模型中的全身炎症反应[8]。
| Cell experiment [1]: | |
Cell lines | Mouse cardiac fibroblasts |
Preparation Method | Mouse cardiac fibroblast cultures were maintained at 37°C and 5% CO2 in complete Dulbecco’s modified Eagle’s medium (DMEM) containing 4.5g/L glucose, 10% FBS, 100U/mL penicillin, and 100μg/mL streptomycin. Mouse cardiac fibroblasts were seeded in Seahorse 24-well tissue culture plates at a density of 4.5×104 cells/well, adherent for 12h, and then treated with CM-4620 (2µM) for 48h. After treatment, the medium was replaced with unbuffered DMEM and the cells were equilibrated for 60min at 37°C in a CO2 -free incubator. After the basal respiration rate was measured, oligomycin (1.5μM), carbonyl cyano-4-(trifluoromethoxyl) phenylhydrazone (FCCP)(1μM), and rotenone/antimycin mixture (1μM) were injected sequentially. Oxygen consumption rate (OCR) was measured in 3-minute increments over a 2-hour period. Basal mitochondrial respiration, ATP-linked respiration, proton leak, maximal respiration, nonmitochondrial respiration, and reserve respiration capacities were determined in whole cells. |
Reaction Conditions | 2μM; 48h |
Applications | CM-4620 treatment reduced cellular oxygen consumption, resulting in a decreased relative utilization of mitochondrial oxidative phosphorylation (OXPHOS) capacity in cells under stress. |
| Animal experiment [2]: | |
Animal models | C57Bl/6 male mice |
Preparation Method | C57Bl/6 male mice (7 weeks old) were housed in groups with 3-5 mice per cage and maintained on a 12-h light-dark cycle with standard chow and sterile tap water ad libitum. Before the experiment, mice were acclimatized for 1 week and then randomly assigned to the following treatment groups: (1) saline group (n=3); (2) saline +20mg/kg CM-4620 group (n=3); (3) cerulein (50μg/kg) (n=4); (4) cerulein + 20mg/kg CM-4620 (n=4). Mice were intraperitoneally injected with 50μg/kg cerulein (or saline as a control) at 7-hour intervals, and CM-4620 (20mg/kg) was administered intraperitoneally at both time points. One hour after the last injection of bluerin/saline, mice were sacrificed by decannulation after carbon dioxide inhalation, and blood and pancreatic tissue were collected for analysis. |
Dosage form | 20mg/kg twice within 7h; i.p. |
Applications | CM-4620 treatment reduced pancreatitis responses and reduced cerulein-induced increases in blood amylase and lipase levels in mice. |
References: | |
| Cas No. | 1713240-67-5 | SDF | |
| 别名 | CM-4620 | ||
| Canonical SMILES | O=C(NC1=NC=C(C2=C(Cl)C=C(OC(F)(F)O3)C3=C2)N=C1)C4=C(C)C=CC=C4F | ||
| 分子式 | C19H11ClF3N3O3 | 分子量 | 421.76 |
| 溶解度 | DMSO : ≥ 100 mg/mL (237.10 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.371 mL | 11.8551 mL | 23.7102 mL |
| 5 mM | 474.2 μL | 2.371 mL | 4.742 mL |
| 10 mM | 237.1 μL | 1.1855 mL | 2.371 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet