N-[2-[2-(Dimethylamino)ethoxy]-4-(1H-pyrazol-4-yl)phenyl]-2,3-dihydro-1,4-benzodioxin-2-carboxamide - CAS 1072959-67-1
Catalog number: 1072959-67-1
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C22H24N4O4
Molecular Weight:
408.45
COA:
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Targets:
ROCK
Description:
SR 3677 is an effective ROCK inhibitor, espectially against ROCK II and it could block the phosphorylation ofmyosin light chain and promote the outflow of aqueous humor in porcine eyes in ex-vivo study. And it was also found to have the potential use to p
Purity:
>98 %
Appearance:
Powder
Synonyms:
N-[2-[2-(Dimethylamino)ethoxy]-4-(1H-pyrazol-4-yl)phenyl]-2,3-dihydro-1,4-benzodioxin-2-carboxamide;SR 3677 hydrochloride;SR3677; SR-3677; SR 3677;
Solubility:
Soluble to 100 mM in water and to 100 mM in DMSO
Storage:
-20ºC Freeze
MSDS:
Inquire
Application:
SR 3677 is an effective ROCK inhibitor, espectially against ROCK II and it could block the phosphorylation ofmyosin light chain and promote the outflow of aqueous humor in porcine eyes in ex-vivo study.
Shelf Life:
As supplied, 2 years from the QC date provided on the Certificate of Analysis, when stored properly
Quantity:
Milligrams-Grams
Density:
1.298
InChIKey:
OQWZIAVXCYIZNN-UHFFFAOYSA-N
InChI:
InChI=1S/C22H24N4O4/c1-26(2)9-10-28-20-11-15(16-12-23-24-13-16)7-8-17(20)25-22(27)21-14-29-18-5-3-4-6-19(18)30-21/h3-8,11-13,21H,9-10,14H2,1-2H3,(H,23,24)(H,25,27)
Canonical SMILES:
CN(C)CCOC1=C(C=CC(=C1)C2=CNN=C2)NC(=O)C3COC4=CC=CC=C4O3
1.Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors.
Feng Y;Yin Y;Weiser A;Griffin E;Cameron MD;Lin L;Ruiz C;Schürer SC;Inoue T;Rao PV;Schröter T;Lograsso P J Med Chem. 2008 Nov 13;51(21):6642-5. doi: 10.1021/jm800986w. Epub 2008 Oct 4.
The identification of a new class of potent and selective ROCK-II inhibitors is presented. Compound 5 (SR-3677) had an IC 50 of approximately 3 nM in enzyme and cell based assays and had an off-target hit rate of 1.4% against 353 kinases, and inhibited only 3 out of 70 nonkinase enzymes and receptors. Pharmacology studies showed that 5 was efficacious in both, increasing ex vivo aqueous humor outflow in porcine eyes and inhibiting myosin light chain phosphorylation.
2.Prognostic value and functional role of ROCK2 in pediatric Ewing sarcoma.
Vieira GM;Roberto GM;Lira RC;Engel EE;Tone LG;Brassesco MS Oncol Lett. 2018 Feb;15(2):2296-2304. doi: 10.3892/ol.2017.7571. Epub 2017 Dec 8.
Ewing's sarcoma (EWS) is a highly aggressive bone cancer that affects children and adolescents. Despite advances in multimodal management, 5-year event-free survival rates for patients presenting with metastases at diagnosis remain at 25%. As key regulators of actin organization, the Rho-associated coiled-coil containing protein kinases, ROCK1 and ROCK2, have been associated with cancer dissemination and poorer prognosis. Recently, ;in vitro; data indicating ROCK2 as a molecular target for the treatment of EWS has been presented. Nonetheless, a deeper exploration of the contribution of this kinase dysregulation in EWS is still necessary. In this regard, the present study aimed to evaluate the expression of ROCK1 and ROCK2 in 23 pediatric tumor samples and to verify the prospect of using their pharmacological inhibition through functional assays. Our results showed positive immunostaining for ROCK1 and ROCK2 in the majority samples (75 and 65%, respectively). A significantly increased risk of incomplete remission in patients with positive immunostaining for ROCK2 was found (P=0.026), though no correlations with other prognostic features (huvos classification, ;FLI1/EWS; status, relapse, metastasis or death) were observed.
3.Pharmacologic inhibition of ROCK2 suppresses amyloid-β production in an Alzheimer's disease mouse model.
Herskowitz JH;Feng Y;Mattheyses AL;Hales CM;Higginbotham LA;Duong DM;Montine TJ;Troncoso JC;Thambisetty M;Seyfried NT;Levey AI;Lah JJ J Neurosci. 2013 Dec 4;33(49):19086-98. doi: 10.1523/JNEUROSCI.2508-13.2013.
Alzheimer's disease (AD) is the leading cause of dementia and has no cure. Genetic, cell biological, and biochemical studies suggest that reducing amyloid-β (Aβ) production may serve as a rational therapeutic avenue to delay or prevent AD progression. Inhibition of RhoA, a Rho GTPase family member, is proposed to curb Aβ production. However, a barrier to this hypothesis has been the limited understanding of how the principal downstream effectors of RhoA, Rho-associated, coiled-coil containing protein kinase (ROCK) 1 and ROCK2, modulate Aβ generation. Here, we report that ROCK1 knockdown increased endogenous human Aβ production, whereas ROCK2 knockdown decreased Aβ levels. Inhibition of ROCK2 kinase activity, using an isoform-selective small molecule (SR3677), suppressed β-site APP cleaving enzyme 1 (BACE1) enzymatic action and diminished production of Aβ in AD mouse brain. Immunofluorescence and confocal microscopy analyses revealed that SR3677 alters BACE1 endocytic distribution and promotes amyloid precursor protein (APP) traffic to lysosomes. Moreover, SR3677 blocked ROCK2 phosphorylation of APP at threonine 654 (T654); in neurons, T654 was critical for APP processing to Aβ. These observations suggest that ROCK2 inhibition reduces Aβ levels through independent mechanisms.
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Chemical Structure

CAS 1072959-67-1 N-[2-[2-(Dimethylamino)ethoxy]-4-(1H-pyrazol-4-yl)phenyl]-2,3-dihydro-1,4-benzodioxin-2-carboxamide

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