CaCCinh-A01
(Synonyms: TMEM16 Blocker I) 目录号 : GC14768
CaCCinh-A01是一种钙激活氯通道（CaCC）TMEM16A抑制剂，对TMEM16A电流的IC50值为7.35 ± 0.86μM。
Cas No.:407587-33-1
Sample solution is provided at 25 µL, 10mM.
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CaCCinh-A01 is an inhibitor of calcium-activated chloride channel (CaCC) TMEM16A, with an IC50 value of 7.35 ± 0.86μM for TMEM16A current [1]. CaCCinh-A01, a potent blocker of Best1 channels, with no effect on intracellular Ca2+ and Ca2+-calmodulin kinase II or CFTR [2]. CaCCinh-A01 has been widely used in animal models to induce vasodilation in small resistance arteries under experimental conditions[3].
In vitro, CaCCinh-A01 treatment for 72 hours it significantly inhibited the proliferation of Te11 cells, FaDu cells, Te1 cells and HeLa cells, with IC50 values of 2.2, 5.8, 37 and 33μM respectively[4]. Treatment with 10μM CaCCinh-A01 for 72 hours significantly inhibited the viability of HT-29 cells, increased intracellular ROS levels, activated the mitochondrial apoptotic pathway, arrested the cell cycle at the S phase, and upregulated the expression of cell cycle-related proteins[5]. Treatment with 30μM CaCCinh-A01 for 24 hours enhanced the proliferation and wound healing ability of BEAS-2B cells, resulting in an increase in intracellular chloride ion content and an increase in FAK phosphorylation levels in cells[6].
In vivo, CaCCinh-A01 treatment via intraperitoneal injection (0.5mg/kg) twice daily for 14 consecutive days alleviated the intestinal damage in C57BL/6 mice caused by whole abdominal irradiation (WAI), accompanied by a decrease in the expression of Anoctamin 1 (ANO1)[7]. Male C57BL/6J mice were intraperitoneally injected with CaCCinh-A01 (17mg/kg/day) once daily for 7 consecutive days could prevent renal fibrosis caused by unilateral ureteral obstruction (UUO), and reduce the expression of fibronectin, α-SMA and collagen in the obstructed kidneys[8].
References:
[1] Shi S, Guo S, Chen Y, et al. Molecular mechanism of CaCCinh-A01 inhibiting TMEM16A channel[J]. Archives of Biochemistry and Biophysics, 2020, 695: 108650.
[2] Liu Y, Zhang H, Huang D, et al. Characterization of the effects of Cl− channel modulators on TMEM16A and bestrophin-1 Ca2+ activated Cl− channels[J]. Pflügers Archiv-European Journal of Physiology, 2015, 467(7): 1417-1430.
[3] Boedtkjer D M B, Kim S, Jensen A B, et al. New selective inhibitors of calcium‐activated chloride channels–T 16 A inh‐A 01, C a CC inh‐A 01 and MONNA–what do they inhibit?[J]. British journal of pharmacology, 2015, 172(16): 4158-4172.
[4] Bill A, Hall M L, Borawski J, et al. Small molecule-facilitated degradation of ANO1 protein[J]. Journal of Biological Chemistry, 2014, 289(16): 11029-11041.
[5] Guo S, Yan H, Wang L, et al. GlyH-101 and CaCCinh-A01 Inhibited HT-29 Proliferation by Activating the Mitochondrial Apoptosis Pathway and Arresting the Cell Cycle[J]. Anticancer Research, 2023, 43(8): 3471-3477.
[6] Wang J, Luo J, Huang W, et al. Increased intracellular Cl− concentration by activating FAK promotes airway epithelial BEAS-2B cells proliferation and wound healing[J]. Archives of Biochemistry and Biophysics, 2020, 680: 108225.
[7] Guo Y, Yuan T, Wang Y, et al. Blockade of calcium-activated chloride channel ANO1 ameliorates ionizing radiation-induced intestinal injury[J]. Journal of Advanced Research, 2025.
[8] Li X L, Liu J, Chen X S, et al. Blockade of TMEM16A protects against renal fibrosis by reducing intracellular Cl− concentration[J]. British Journal of Pharmacology, 2022, 179(12): 3043-3060.
CaCCinh-A01是一种钙激活氯通道（CaCC）TMEM16A抑制剂，对TMEM16A电流的IC50值为7.35 ± 0.86μM[1]。作为Best1通道的有效阻断剂，CaCCinh-A01不影响细胞内Ca²⁺、钙调蛋白激酶II或CFTR功能[2]。CaCCinh-A01已广泛应用于动物模型中诱导实验条件下小阻力动脉的血管舒张[3]。
在体外，CaCCinh-A01处理72小时可显著抑制Te11、FaDu、Te1和HeLa细胞增殖，IC50值分别为2.2μM、5.8μM、37μM和33μM[4]。10μM的CaCCinh-A01处理HT-29细胞72小时能抑制细胞活力，增加细胞内ROS水平，激活线粒体凋亡通路，使细胞周期阻滞于S期，并上调周期相关蛋白表达[5]。30μM的CaCCinh-A01处理BEAS-2B细胞24小时可yiz细胞增殖和伤口愈合能力，增加细胞内氯离子含量并提高FAK磷酸化水平[6]。
在体内，C57BL/6小鼠每日两次腹腔注射CaCCinh-A01（0.5mg/kg；持续14天）可减轻全腹部照射（WAI）引起的肠道损伤，并伴随Anoctamin 1（ANO1）表达下降[7]。雄性C57BL/6J小鼠每日腹腔注射17mg/kg CaCCinh-A01（持续7天）能预防单侧输尿管梗阻（UUO）引起的肾纤维化，并降低梗阻肾脏中纤连蛋白、α-SMA和胶原的表达[8]。
| Cell experiment [1]: | |
Cell lines | HT-29 cells |
Preparation Method | HT-29 cells were cultured in a McCoy’s 5A medium supplemented with 10% fetal bovine serum and penicillin-streptomycin (1%) at 37˚C in a humid environment composed of 5% CO2 and 95% air. Cells were treated with different concentrations of CaCCinh-A01 (1, 10, 100, and 1000μM) for 24, 48, or 72h. The absorbance value was measured on an enzyme standard meter. The number of apoptotic cells was quantified using flow cytometry. |
Reaction Conditions | 1, 10, 100, and 1000μM; 24, 48, or 72h |
Applications | CaCCinh-A01 treatment significantly inhibited cell proliferation of HT-29 cells and caused apoptosis in a dose- and time-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male C57BL/6 mice |
Preparation Method | Male C57BL/6 mice (19-21g) were randomly assigned to 2 groups, IR and IR+CaCCinh-A01. Mice received intraperitoneal (i.p.) injections of the CaCCinh-A01 at 0.5mg/kg, administered twice daily. The mice were irradiated with doses of 15Gy, and 17Gy. In the 15Gy cohort, a total of forty-eight mice were included, with twelve mice per group; In the 17Gy cohort, a total of sixty-four mice were included, with sixteen mice per group. On the 14th day post-irradiation, the colons of mice were collected, longitudinally opened, photographed, and the tumor numbers were recorded. |
Dosage form | 0.5mg/kg twice daily for 14 days; i.p. |
Applications | CaCCinh-A01 treatment significantly attenuated IR-induced intestinal damage in mice and improve survival rates. |
References: | |
| Cas No. | 407587-33-1 | SDF | |
| 别名 | TMEM16 Blocker I | ||
| 化学名 | (R)-6-(tert-butyl)-2-(furan-2-carboxamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid | ||
| Canonical SMILES | OC(C1=C(NC(C2=CC=CO2)=O)SC3=C1CC[C@H](C3)C(C)(C)C)=O | ||
| 分子式 | C18H21NO4S | 分子量 | 347.43 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml | 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。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8783 mL | 14.3914 mL | 28.7828 mL |
| 5 mM | 575.7 μL | 2.8783 mL | 5.7566 mL |
| 10 mM | 287.8 μL | 1.4391 mL | 2.8783 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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