GSK429286A

Katalognr.S1474 Batch:S147402

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Tekniska data

Formel

C21H16F4N4O2
Molekylvikt 432.37 CAS-nr. 864082-47-3
Löslighet (25°C)* In vitro DMSO 86 mg/mL (198.9 mM)
Ethanol 5 mg/mL (11.56 mM)
Water Insoluble
In Vivo (Tillsätt lösningsmedel till produkten individuellt och i ordning.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml betyder svårlösligt eller olösligt.
* Vänligen notera att Selleck testar lösligheten för alla förbindelser internt, och den faktiska lösligheten kan skilja sig något från publicerade värden. Detta är normalt och beror på små variationer mellan olika partier.
* Rumstempererad frakt (Stabilitetstester visar att denna produkt kan fraktas utan några kylåtgärder.)

Beredning av stamlösningar

Biologisk aktivitet

Beskrivning GSK429286A (RHO-15) är en selektiv hämmare av ROCK1 och ROCK2 med IC50 på 14 nM respektive 63 nM.
Mål
ROCK1
(Cell-free assay)		 ROCK2
(Cell-free assay)
14 nM 63 nM
In vitro GSK429286A slightly inhibits RSK and p70S6K with IC50 of 0.78 μM and 1.94 μM, respectively. This compound significantly inhibits rat aortic ring dilation with IC50 of 190 nM. This chemical at 1 μM reduces ROCK2 activity over 20-fold, under conditions in which the only other kinase tested that is significantly inhibited is MSK1 whose activity is reduced ~5-fold. It is a more selective ROCK2 inhibitor than the widely utilized ROCK inhibitor Y-27632 as assessed on kinase-specificity panel, and does not significantly inhibit LRRK2 even at doses as high as 30 μM (500-fold higher than IC50 of inhibition of ROCK2). Like GSK269962A but not sunitinib, this compound treatment at 10 μM ablates basal or G14V-Rho mutant induced phosphorylation of MYPT at Thr850 in HEK-293 cells to a similar extent as H-1152 and Y-27632, consistent with ROCK mediating this phosphorylation, whereas it does not inhibit ERM protein phosphorylation either in the presence or absence of G14V-Rho.
In Vivo GSK429286A has 61% oral bioavailability in male Sprague-Dawley rats. Oral administration of this compound at single doses of 3-30 mg/kg dramatically reduces mean arterial pressure in the spontaneously hypertensive rats (SHRs) in a dose-dependent manner, with a maximum decrease of 50 mmHg after approximately 2 hours treatment at dose of 30 mg/kg.
Egenskaper Större selektivitet än Y-27632.

Protokoll (från referens)

Djurstudie:[1]
  • Djurmodeller

    Male spontaneously hypertensive rats (SHRs)

  • Doseringar

    ~30 mg/kg

  • Administrering

    Oral gavage

Referenser

  • https://pubmed.ncbi.nlm.nih.gov/17201405/
  • https://pubmed.ncbi.nlm.nih.gov/19740074/

Kundvalidering av produkt

<p>ROCK antagonists interfere with infection-induced changes in cell shape, but do not reduce HCMV yield. (<em>A</em>) ROCK antagonists block actin reorganization after infection. Fibroblasts were treated with solvent (DMSO) or drug (10 uM Y27632 or 140 nM GSK429286A) beginning 1 h after mock infection or infection with WT virus. Cells received fresh medium containing solvent or drug every 24 h. Cultures were assayed for actin using labeled phalloidin (red), pUL37 (green), and DNA (blue). (<em>B</em>) ROCK antagonist blocks cell rounding at 24 hpi. Fibroblasts were treated with solvent or drug beginning 1 h after mock infection or infection with WT virus. Cultures received fresh medium with drug every 24 h and were analyzed by treatment with 5 μM fluorophore calcein red-orange AM for 1 h, followed by spinning disk confocal Z-stack live cell imaging and reconstruction of 3D images. (<em>C</em>) ROCK activity does not influence virus yield. Fibroblasts were treated with solvent or ROCK antagonists beginning 1 h after infection with WT HCMV. Cultures received fresh medium with drug every 24 h, and extracellular virus yields were determined by plaque assay.</p>

Data från [ Proc Natl Acad Sci U S A , 2014 , 111(12), E1140-8 ]

HLMVECs grown to confluence in six-well plates were preincubated with vehicle (0.1% DMSO), Y27632 (10 uM), or GSK429286 (10 uM) for 2 hours, followed by treatment with 1 EU/ml LPS for 2 hours. Western blot analysis was performed for diphosphorylated myosin light chain (ppMLC) and β-actin.

Data från [ Am J Respir Cell Mol Biol , 2014 , 50(1), 170-9 ]

ROCK is required for ETAR-induced YAP/TAZ activation. Serum-starved HCT116 cells were pretreated with GSK429286 (0.5 μmol/L) or Y27632 (1 μmol/L) for 4 hours, followed by treatment with 100 nmol/L of ET-1 for 1 hour. Phosphorylation and protein levels of YAP/TAZ were determined by immunoblotting.

Data från [ , , Cancer Res, 2017, 77(9):2413-2423 ]

The location of E-cadherin and β-catenin was detected by immunofluorescence staining. Data are mean ± SD of four independent experiments

Data från [ , , Respir Res, 2017, 18(1):111 ]

Sellecks GSK429286A Har citerats av 23 Publikationer

Chemically induced revitalization of damaged hepatocytes for regenerative liver repair [ iScience, 2023, 26(12):108532] PubMed: 38144457
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7] PubMed: 34997030
Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment [ Cancer Sci, 2020, 112(1):133-143] PubMed: 33067904
Complementary roles of platelet αIIbβ3 integrin, phosphatidylserine exposure and cytoskeletal rearrangement in the release of extracellular vesicles [ Atherosclerosis, 2020, 310:17-25] PubMed: 32877806
The TGF-b/SOX4 axis and ROS-driven autophagy co-mediate CD39 expression in regulatory T-cells. [ FASEB J, 2020, 22] PubMed: 32319705
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004] PubMed: 31740922
A Combined Approach Reveals a Regulatory Mechanism Coupling Src's Kinase Activity, Localization, and Phosphotransferase-Independent Functions. [ Mol Cell, 2019, 74(2):393-408] PubMed: 30956043
DRUGPATH - a novel bioinformatic approach identifies DNA-damage pathway as a regulator of size maintenance in human ESCs and iPSCs [ Sci Rep, 2019, 9(1):1897] PubMed: 30760778
Rho-associated kinase and zipper-interacting protein kinase, but not myosin light chain kinase, are involved in the regulation of myosin phosphorylation in serum-stimulated human arterial smooth muscle cells [ PLoS One, 2019, 14(12):e0226406] PubMed: 31834925
Fibronectin regulates the self-renewal of rabbit limbal epithelial stem cells by stimulating the Wnt11/Fzd7/ROCK non-canonical Wnt pathway [ Exp Eye Res, 2019, 185:107681] PubMed: 31150636

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