SR3677

SR3677 is an isoform-selective inhibitor of ROCK2 kinase activity.

Product information

CAS Number: 1072959-67-1

Molecular Weight: 408.45

Formula: C22H24N4O4

Chemical Name: N-[2-[2-(Dimethylamino)ethoxy]-4-(1H-pyrazol-4-yl)phenyl]-2,3-dihydro-1,4-benzodioxine-3-carboxamide

Smiles: CN(C)CCOC1=CC(=CC=C1NC(=O)C1COC2=CC=CC=C2O1)C1=CNN=C1

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)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

SR3677 has an IC50 of ~3 nM in enzyme and cell based assays and has an off-target hit rate of 1.4% against 353 kinases, and inhibits only 3 out of 70 nonkinase enzymes and receptors. The IC50 value of SR3677 for ROCK-I is 56±12 nM. The hydrophobic interaction of the benzodioxane phenyl ring with the hydrophobic surface of the pocket is the dominating factor that contributes to the high potency of SR3677.

In Vivo:

ExVivo: Pharmacology studies shows that SR3677 is efficacious in both, increasing ex vivo aqueous humor outflow in porcine eyes and inhibiting myosin light chain phosphorylation. Continuous exposure of 25 µM SR3677 increases the outflow facility by 60% at 1 h perfusion, increasing to 70–80% for the 2–5 h time points.

References:

1. Vieira GM, Roberto GM, Lira RC, Engel EE, Tone LG, Brassesco MS. Prognostic value and functional role of ROCK2 in pediatric Ewing sarcoma. Oncol Lett. 2018 Feb;15(2):2296-2304. doi: 10.3892/ol.2017.7571. Epub 2017 Dec 8. PubMed PMID: 29434937; PubMed Central PMCID: PMC5777092.
2. Kasahara DI, Mathews JA, Park CY, Cho Y, Hunt G, Wurmbrand AP, Liao JK, Shore SA. ROCK insufficiency attenuates ozone-induced airway hyperresponsiveness in mice. Am J Physiol Lung Cell Mol Physiol. 2015 Oct 1;309(7):L736-46. doi: 10.1152/ajplung.00372.2014. Epub 2015 Aug 14. PubMed PMID: 26276827; PubMed Central PMCID: PMC4593838.
3. Herskowitz JH, Feng Y, Mattheyses AL, Hales CM, Higginbotham LA, Duong DM, Montine TJ, Troncoso JC, Thambisetty M, Seyfried NT, Levey AI, Lah JJ. Pharmacologic inhibition of ROCK2 suppresses amyloid-β production in an Alzheimer's disease mouse model. J Neurosci. 2013 Dec 4;33(49):19086-98. doi: 10.1523/JNEUROSCI.2508-13.2013. PubMed PMID: 24305806; PubMed Central PMCID: PMC3850036.

Products are for research use only. Not for human use.