RKI-1447

RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer. 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 suppressed phosphorylation of the ROCK substrates MLC-2 and MYPT-1 in human cancer cells.

Product information

CAS Number: 1342278-01-6

Molecular Weight: 326.37

Formula: C16H14N4O2S

Chemical Name: 1-(3-Hydroxybenzyl)-3-(4-(pyridin-4-yl)thiazol-2-yl)urea

Smiles: OC1C=CC=C(CNC(=O)NC2=NC(=CS2)C2C=CN=CC=2)C=1

InChiKey: GDVRVPIXWXOKQO-UHFFFAOYSA-N

InChi: InChI=1S/C16H14N4O2S/c21-13-3-1-2-11(8-13)9-18-15(22)20-16-19-14(10-23-16)12-4-6-17-7-5-12/h1-8,10,21H,9H2,(H2,18,19,20,22)

Technical Data

Appearance: Solid Power.

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

Solubility: 10 mM 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:

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 has 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. 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. RKI-1447 inhibits mammary tumor growth by 87% and on average the mammary tumors from RKI-1447 treated mice are 7.7 fold smaller compared to those tumors from mice treated with the vehicle control.

References:

1. Patel RA, et al. RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer. Cancer Res. 2012 Oct 1;72(19):5025-34.

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