<Suppliers Price>

SR-3677

Names

[ CAS No. ]:
1072959-67-1

[ Name ]:
SR-3677

[Synonym ]:
rs0088
hms3244c10
1,4-Benzodioxin-2-carboxamide, N-[2-[2-(dimethylamino)ethoxy]-4-(1H-pyrazol-4-yl)phenyl]-2,3-dihydro-
hms3244d09
N-{2-[2-(Dimethylamino)ethoxy]-4-(1H-pyrazol-4-yl)phenyl}-2,3-dihydro-1,4-benzodioxine-2-carboxamide
sr3677
hms3244c09
SR-3677

Biological Activity

[Description]:

SR-3677 is a potent and selective ROCK-II inhibitor with an IC50 of ~3 nM.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy
Signaling Pathways >> Cell Cycle/DNA Damage >> ROCK
Signaling Pathways >> Stem Cell/Wnt >> ROCK
Signaling Pathways >> TGF-beta/Smad >> ROCK
Research Areas >> Cancer

[Target]

ROCK-II:3 nM (IC50)

ROCK-I:56 nM (IC50)


[In Vitro]

SR-3677 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 SR-3677 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 SR-3677[1].

[In Vivo]

ExVivo: Pharmacology studies shows that SR-3677 is efficacious in both, increasing ex vivoaqueous humor outflow in porcine eyes and inhibiting myosin light chain phosphorylation. Continuous exposure of 25 µM SR-3677 increases the outflow facility by 60% at 1 h perfusion, increasing to 70–80% for the 2–5 h time points[1].

[Kinase Assay]

Assays are performed using the STK2 kinase system from Cisbio. 5 μL mixture of a 1 μM STK2 substrate and ATP (ROCK-I: 4 μM; ROCK-II: 20 μM) in STK-buffer is added to the wells. 20 nL of test compounds (SR-3677) is dispensed. Reaction is started by addition of 5 μL of 2.5 nM. ROCK-I or 0.5 nM ROCK-II in STK-buffer. After 4 h at RT the reaction is stopped by addition of 10 μL of 1x antibody and 62.5 nM Sa-XL in detection buffer[1].

[References]

[1]. Feng Y, et al. Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. J Med Chem. 2008 Nov 13;51(21):6642-5.


[Related Small Molecules]

Y-27632 2HCl | Fasudil Hydrochloride | KD025(SLx-2119) | Narciclasine | Y-39983 HCl | Thiazovivin | GSK429286A | GSK180736A | GSK 269962 | TC-S 7001 | K-115 | RKI-1447 | LX7101 | Chroman 1 | H-1152 (dihydrochloride)

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
646.9±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C22H24N4O4

[ Molecular Weight ]:
408.450

[ Flash Point ]:
345.0±31.5 °C

[ Exact Mass ]:
408.179749

[ PSA ]:
92.20000

[ LogP ]:
2.34

[ Vapour Pressure ]:
0.0±1.9 mmHg at 25°C

[ Index of Refraction ]:
1.632

[ Storage condition ]:
-20℃

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds