[CAS NO. 1342278-01-6] RKI-1447

Name: RKI-1447
Brand: Arctom Scientific
SKU: SLK-S7195

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PRODUCTS SPECIFICATIONS [1342278-01-6]

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Catalog

SLK-S7195

Brand

Selleck

CAS

1342278-01-6

DESCRIPTION [1342278-01-6]

Overview

MDL	MFCD26142658
Molecular Weight	326.37
Molecular Formula	C16H14N4O2S
SMILES	O=C(NC1=NC(C2=CC=NC=C2)=CS1)NCC3=CC=CC(O)=C3

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Concentration Volume Mass	1 mg	5 mg	10 mg
1 mM	3.0640 mL	15.3200 mL	30.6401 mL
5 mM	0.6128 mL	3.0640 mL	6.1280 mL
10 mM	0.3064 mL	1.5320 mL	3.0640 mL
50 mM	0.0613 mL	0.3064 mL	0.6128 mL

Description

RKI-1447 is a potent inhibitor of and , with of 14.5 nM and 6.2 nM, respectively, has anti-invasive and antitumor activities.

Targets

ROCK2 ^[1] (Cell-free assay)	ROCK1 ^[1] (Cell-free assay)
6.2 nM	14.5 nM

In vitro

RKI-1447 is a cell-permeable pyridylthiazolyl-urea that acts as a potent, ATP site-targeting Rho Kinase inhibitor, displaying much reduced potency against PKA, PKN1/PRK1, p70S6K/RPS6kB1, AKT1, MRCKa/CDC42BPA (85.5%, 80.5%, 61.9%, 56.0%, and 50.4% inhibition, respectively, by 1 µM RKI-1447) or 15 other kinases. Crystal structures of the RKI-1447/ROCK1 complex reveals that RKI-1447 is a Type I kinase inhibitor that binds the ATP binding site through interactions with the hinge region and the DFG motif. RKI-1447 suppresses phosphorylation of the ROCK substrates MLC-2 and MYPT-1 in human cancer cells, but had no effect on the phosphorylation levels of the AKT, MEK, and S6 kinase at concentrations as high as 10 μM. RKI-1447 is also highly selective at inhibiting ROCK-mediated cytoskeleton re-organization (actin stress fiber formation) following LPA stimulation, but does not affect PAK-meditated lamellipodia and filopodia formation following PDGF and Bradykinin stimulation. RKI-1447 inhibits migration, invasion and anchorage-independent tumor growth of breast cancer cells.

In vivo

RKI-1447 is highly effective at inhibiting the outgrowth of mammary tumors in a transgenic mouse model. Tumors from mice treated with the RKI-1447 increases in size with an average percent change in tumor volume of only 8.8%. Thus, RKI-1447 inhibited mammary tumor growth by 87%, and on average the mammary tumors from Compared with those tumors from mice treated with the vehicle control, RKI-1447 treated mice are 7.7-fold smaller. RKI-1447 treatments does not result in mouse weight loss.

References

[1] Patel RA, et al. Cancer Res, 2012, 72(19), 5025-5034.
[2] Pireddu R, et al. Medchemcomm, 2012, 3(6), 699-709.