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Chemical Structure| 2253744-54-4 Chemical Structure| 2253744-54-4

Structure of Dooku1
CAS No.: 2253744-54-4

Chemical Structure| 2253744-54-4

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Dooku1 is a reversible Yoda1 antagonist that effectively disrupts Yoda1-induced Piezo1 channel activity, making it potentially valuable in vascular physiology and related disease research.

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Product Details of Dooku1

CAS No. :2253744-54-4
Formula : C13H9Cl2N3OS
M.W : 326.20
SMILES Code : ClC1=C(C(Cl)=CC=C1)CSC2=NN=C(C3=CC=CN3)O2
MDL No. :MFCD32174346
InChI Key :MNPOBXLPCWFONX-UHFFFAOYSA-N
Pubchem ID :137321150

Safety of Dooku1

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Isoform Comparison

Biological Activity

Description
Dooku1 acts as a reversible antagonist of Yoda1, with IC50 values of 1.3 μM and 1.5 μM for Yoda1-induced Ca2+ entry in HEK 293 cells and HUVECs at a Yoda1 concentration of 2 μM, respectively. It interferes with Yoda1-induced Piezo1 channel activity and inhibits Yoda1-induced relaxation of the aorta. Dooku1 is applicable for research in vascular physiology and disease[1].

In Vitro:

Cell Line
Concentration Treated Time Description References
BRIN-BD11 cells 10 μM 15 minutes inhibited Yoda1-induced Ca2+ influx Sci Rep. 2019 Nov 14;9(1):16876
INS-1 cells 10 μM 15 minutes inhibited Yoda1-induced Ca2+ influx Sci Rep. 2019 Nov 14;9(1):16876
HUVECs 10 μM 30 minutes To test the inhibitory effect of Dooku1 on endogenous Piezo1 channels in HUVECs, results showed that Dooku1 inhibited Yoda1-induced Ca2+ entry Br J Pharmacol. 2018 May;175(10):1744-1759
MLO-Y4 cells 40 μM 30 minutes Dooku1 inhibited fluid flow shear stress (FFSS)-induced intracellular Ca2+ signaling and Cx43 hemichannels activation Cell Biosci. 2022 Dec 1;12(1):191
human red blood cells 1 µM to 100 µM immediately observed Study the dose-dependent effect of Dooku1, found that Dooku1 has a direct dose-dependent effect in the range of 1-10 µM, triggering calcium entry and activating the Gárdos channel. Front Physiol. 2023 Jul 10;14:1222983
human red blood cells 10 µM 15 minutes Investigate the inhibitory effect of Dooku1 on Yoda1-induced effects, found that Dooku1 itself can trigger calcium entry and activate the Gárdos channel. Front Physiol. 2023 Jul 10;14:1222983
human eosinophil cell line AML14.3D10 10 µM 3 minutes Inhibited Yoda1-induced Piezo1 activity, significantly reducing Ca2+ elevation Biomolecules. 2024 Sep 14;14(9):1157
Human aortic smooth muscle cells (HAoSMC) 5 μmol/L 7 days Dooku1 inhibited Yoda1-induced calcification in HAoSMCs, reducing calcium deposition in the extracellular matrix. Front Physiol. 2022 Nov 10;13:1037230
HEK 293 cells 10 μM 30 minutes To test the inhibitory effect of Dooku1 on Yoda1-induced Piezo1 channel activity, results showed that Dooku1 effectively inhibited Yoda1-induced Ca2+ entry Br J Pharmacol. 2018 May;175(10):1744-1759

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6 mice Mouse thoracic aorta rings In vitro culture 10 μM Single administration, lasting 20 minutes To test the inhibitory effect of Dooku1 on Yoda1-induced aortic relaxation, results showed that Dooku1 effectively inhibited Yoda1-induced aortic relaxation Br J Pharmacol. 2018 May;175(10):1744-1759
Sprague Dawley rats Thoracic aorta rings Tissue bath 10 μM 1-hour incubation Dooku1 caused direct contraction in thoracic aorta rings without PVAT but did not alter PE-induced contraction. Pharmacol Res. 2022 Jan;175:105995
C57BL/6 mice Intracerebral hemorrhage model Intraperitoneal injection 5, 10, and 20 mg/kg Four administrations at 0.5, 12, 24, and 48 hours post-operation Dooku1 significantly alleviated brain edema, myelin sheath loss, and degeneration in injured tissue, substantially reduced oligodendrocyte apoptosis, and significantly improved neurological function. Additionally, Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway. Neural Regen Res. 2023 Aug;18(8):1750-1756
C57BL/6J mice Tibial compression model Intraperitoneal injection 5 mg/kg Single injection, 4 hours before mechanical loading Dooku1 inhibited mechanical loading-induced opening of Cx43 hemichannels Cell Biosci. 2022 Dec 1;12(1):191
Mice Murine neocortex In vitro administration 10 µM and 20 µM Dooku1 significantly reduced the SIC frequency and activity induced by Yoda1, and when applied alone, it significantly decreased the rise time of SICs. Int J Mol Sci. 2024 Apr 3;25(7):3994

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

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3.07mL

0.61mL

0.31mL

15.33mL

3.07mL

1.53mL

30.66mL

6.13mL

3.07mL

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