TRPC6 inhibitor
(Synonyms: 4-[[(1R,2R)-2-[(3R)-3-氨基-1-哌啶基]-2,3-二氢-1H-茚-1-基]氧基]-3-氯苯甲腈二盐酸盐) 目录号 : GC13218
A TRPC6 channel blocker
Cas No.:1333207-63-8
Sample solution is provided at 25 µL, 10mM.
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SAR7334 hydrochloride is a potent and specific TRPC6 inhibitor, inhibiting TRPC6 currents with IC50 of 7.9 nM.
SAR7334 inhibits TRPC6, TRPC3 and TRPC7-mediated Ca2+ influx into cells with IC50s of 9.5, 282 and 226 nM[1][2][3], whereas TRPC4 and TRPC5-mediated Ca2+ entry is not affected. SAR7334 (1 μM) results in a major block of the Ang II-evoked calcium influx in the podocytes[1]. SAR7334 (1 μM) has negligible effect on SOCE[2]. SAR7334 dose-dependently reduces TRPC6 currents with an IC50 of 7.9 nM. SAR7334 (100 nM) substantially reduces TRPC6 currents[3].
SAR7334 (10 mg/kg, p.o.) suppresses TRPC6-dependent acute HPV in isolated perfused lungs from mice. SAR7334 demonstrates that it is suitable for chronic oral administration. In an initial short-term study, SAR7334 does not change mean arterial pressure in spontaneously hypertensive rats (SHR)[3].
[1]. Ilatovskaya DV, et al. The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling. Sci Rep. 2017 Mar 22;7(1):299.
[2]. Chauvet S, et al. Pharmacological Characterization of the Native Store-Operated Calcium Channels of Cortical Neurons from Embryonic Mouse Brain. Front Pharmacol. 2016 Dec 12;7:486.
[3]. Maier T, et al. Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol-sensitive TRPC cation channels. Br J Pharmacol. 2015 Jul;172(14):3650-60.
Animal experiment: | Adult male (6 months old) spontaneously hypertensive rats (SHR) are treated on two consecutive days. On day one, the animals receive 1 mL/kg vehicle by oral gavage. After 24 h, rats receive either vehicle alone or are treated with 10 mg/kg SAR7334. Telemetric measurement of BP is performed. In brief, a telemetric device (TL11M2-C50-PXT PMP) is placed between the aorta and the vena cava and the catheter tip of the transmitter is inserted into the aorta. Systolic BP, diastolic BP and heart rate are acquired continuously at a sampling rate of 500 Hz and data are stored as 5 min averages. Mean arterial pressure is calculated from systolic and diastolic pressure and low-pass filtered using the fast Fourier transform function of the vendor software for better visualization of time-dependent BP variations. For statistical analysis, raw data are averaged over a 6 h period starting 2 h after application of vehicle or SAR7334. This interval corresponds to the maximal plasma levels of SAR7334. Baseline data are sampled over the same time interval on the day before treatment. |
References: [1]. Ilatovskaya DV, et al. The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling. Sci Rep. 2017 Mar 22;7(1):299. | |
| Cas No. | 1333207-63-8 | SDF | |
| 别名 | 4-[[(1R,2R)-2-[(3R)-3-氨基-1-哌啶基]-2,3-二氢-1H-茚-1-基]氧基]-3-氯苯甲腈二盐酸盐 | ||
| 化学名 | 4-(((1R,2R)-2-((R)-3-aminopiperidin-1-yl)-2,3-dihydro-1H-inden-1-yl)oxy)-3-chlorobenzonitrile dihydrochloride | ||
| Canonical SMILES | ClC1=C(O[C@]2([H])C3=CC=CC=C3C[C@@]2([H])N4CCC[C@](N)([H])C4)C=CC(C#N)=C1.Cl.Cl | ||
| 分子式 | C21H24Cl3N3O | 分子量 | 440.79 |
| 溶解度 | DMF: 1 mg/mL,DMSO: 15 mg/mL,Ethanol: 25 mg/mL,Ethanol:PBS (pH 7.2) (1:5): 0.16mg/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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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2687 mL | 11.3433 mL | 22.6865 mL |
| 5 mM | 0.4537 mL | 2.2687 mL | 4.5373 mL |
| 10 mM | 0.2269 mL | 1.1343 mL | 2.2687 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
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet