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]。