Dooku1
(Synonyms: 2-((2,6-二氯苄基)硫基)-5-(1H-吡咯-2-基)-1,3,4-恶二唑) 目录号 : GC38553
Dooku1,作为可逆的Yoda1拮抗剂,对 Yoda1诱导的Ca2+进入HUVEC中具有浓度依赖性抑制作用,IC50为1.49µM。
Cas No.:2253744-54-4
Sample solution is provided at 25 µL, 10mM.
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Dooku1, a reversible Yoda1 antagonist, has a concentration-dependent inhibitory effect against Yoda1-induced Ca2+ entry in HUVECs, acting with an IC50 of 1.49µM. Dooku1 can antagonize Yoda1‐evoked activation of Piezo1 and aortic relaxation and be used for research related to hypertensive nephropathy[1].
Dooku1 pretreatment (5µM) in rat cauda epididymal epithelial cells significantly suppressed the Yoda1-stimulated Ca2+ response. The Yoda1-stimulated Ca2+ response was abolished when ambient Ca2+ was removed [2]. Dooku1 inhibited 2µM Yoda1‐induced Ca2+‐entry with IC50 of 1.3µM in HEK 293 cells [1].
Dooku1 treatment (10 mg/kg) significantly increased the right turn percentage 72 hours after intracerebral hemorrhage (ICH) among Male adult C57BL/6 mice in the corner turn test. Compared with the ICH +vehicle group, Dooku1 treatment (10 mg/kg) significantly decreased the brain water content at 24 and 72 hours after ICH. A moderate dose (10 mg/kg) of the Piezo1 antagonist Dooku1 could relieve neurological impairment and myelin damage among C57BL/6 mice[3].
References:
[1]. Evans EL, Cuthbertson K, Endesh N, Rode B, Blythe NM, Hyman AJ, et al. Yoda1 analogue (Dooku1) which antagonizes Yoda1-evoked activation of Piezo1 and aortic relaxation. Br J Pharmacol. 2018;175(10):1744-59. Epub 20180406. doi: 10.1111/bph.14188. PubMed PMID: 29498036.
[2]. Gao DD, Huang JH, Ding N, Deng WJ, Li PL, Mai YN, et al. Mechanosensitive Piezo1 channel in rat epididymal epithelial cells promotes transepithelial K(+) secretion. Cell Calcium. 2022;104:102571. Epub 20220315. doi:10.1016/j.ceca.2022.102571. PubMed PMID: 35314382.
[3]. Qu J, Zong HF, Shan Y, Zhang SC, Guan WP, Yang Y, et al. Piezo1 suppression reduces demyelination after intracerebral hemorrhage. Neural Regen Res. 2023;18(8):1750-6. doi: 10.4103/1673-5374.361531.PubMed PMID: 36751801; PubMed Central PMCID: PMCPMC10154511.
Dooku1,作为可逆的Yoda1拮抗剂,对 Yoda1诱导的Ca2+进入HUVEC中具有浓度依赖性抑制作用,IC50为1.49µM。Dooku1可以拮抗Yoda1诱发的Piezo1激活和主动脉舒张并且可用于高血压肾病相关研究[1]。
Dooku1预处理(5µM)大鼠附睾上皮细胞显著抑制Yoda1刺激的Ca2+反应。当环境中Ca2+被去除时,Yoda1刺激的Ca2+反应被消除[2]。Dooku1在HEK 293细胞中抑制 2µM Yoda1 诱导的Ca2+ 内流,IC50为1.3µM[1]。
Dooku1治疗 (10 mg/kg) 显著增加了转弯试验中雄性成年 C57BL/6 小鼠脑出血(ICH) 后 72小时的右转率。与ICH +对照组相比,Dooku1治疗(10 mg/kg)显著降低了ICH后24小时和72小时的脑含水量。中等剂量(10 mg/kg)的 Piezo1 拮抗剂 Dooku1可以缓解C57BL/6 小鼠神经损伤和髓鞘损伤[3]。
| Cell experiment [1]: | |
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Cell lines |
Rat podocyte cell line C7 |
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Preparation Method |
Cells were pretreated with Dooku1(10µM) for 30min or Rac inhibitor EHT 1864 (50µM) for 2h, prior to Yoda1 (3µM) or vehicle stimulation. |
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Reaction Conditions |
10µM Dooku1 for 30min |
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Applications |
Yoda1-induced upregulation of Pai1, Sgk1, and Mcp1 was significantly inhibited by Dooku1 via Yoda1-Piezo1 signaling. |
| Animal experiment [2]: | |
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Animal models |
Male adult C57BL/6 mice (aged 8-10 weeks, weighing 22-30g) |
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Preparation Method |
Dooku1 was dissolved in dimethyl sulfoxide to a final concentration of less than 0.1%. Dooku1 (5, 10, 20mg/kg) was intraperitoneally administered at 24 and 72 hours after intracerebral hemorrhage (ICH) to evaluate the effects of Dooku1 on neurological function. |
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Dosage form |
5, 10, 20mg/kg twice, intraperitoneal injection |
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Applications |
In the modified Garcia test, treatment with 5mg/kg Dooku1 did not affect the score at 24 and 72 hours after ICH, treatment with 10 and 20 mg/kg Dooku1 significantly improved the score at 72 hours after ICH, but only 10 mg/kg Dooku1 significantly improved the score 24 hours after ICH. |
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References: [1]. Ogino S, Yoshikawa K, Nagase T, Mikami K, Nagase M. Roles of the mechanosensitive ion channel Piezo1 in the renal podocyte injury of experimental hypertensive nephropathy.Hypertens Res. 2024;47(3):747-59. Epub 20231225. doi: 10.1038/s41440-023-01536-z. PubMed PMID: 38145990. | |
| Cas No. | 2253744-54-4 | SDF | |
| 别名 | 2-((2,6-二氯苄基)硫基)-5-(1H-吡咯-2-基)-1,3,4-恶二唑 | ||
| Canonical SMILES | ClC1=C(C(Cl)=CC=C1)CSC2=NN=C(C3=CC=CN3)O2 | ||
| 分子式 | C13H9Cl2N3OS | 分子量 | 326.2 |
| 溶解度 | DMSO: 125 mg/mL (383.20 mM) | 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 | 3.0656 mL | 15.328 mL | 30.656 mL |
| 5 mM | 0.6131 mL | 3.0656 mL | 6.1312 mL |
| 10 mM | 0.3066 mL | 1.5328 mL | 3.0656 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 |
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| % 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。
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet