RKI-1447

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H14N4O2S
Molecular Weight	326.373
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=CC(CNC(=O)NC2=NC(=CS2)C3=CC=NC=C3)=CC=C1

InChI

InChIKey=GDVRVPIXWXOKQO-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C16H14N4O2S
Molecular Weight	326.373
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22846914
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/?term=23275831 | https://www.ncbi.nlm.nih.gov/pubmed/27841867 | DOI:10.3781/j.issn.1000-7431.2015.11.578

RKI 1447 is a potent and selective ROCK inhibitor. It displays anti-invasive and antitumor activities in breast cancer cells. RKI-1447 can inhibit the proliferation, migration and invasion abilities of ovarian cancer cells. RKI 1447 exhibits cytotoxic and cytostatic effects on VHL-deficient clear cell renal cell carcinoma (CC-RCC), making them candidate novel therapeutics for CC-RCC. RKI-1447 significantly inhibited mammary tumor growth in animal models.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Rho-associated protein kinase 1 20 Target ID: CHEMBL3231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=23275831	Inhibitor 8297		8.0 nM [IC50]
Rho-associated protein kinase 2 25 Target ID: CHEMBL2973 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=23275831	Inhibitor 8297		6.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22846914	Primary	Preclinical	Unknown Approved Use Unknown
Clear cell renal cell carcinoma 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27841867	Primary	Basic research	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: DOI: 10.3781/j.issn.1000-7431.2015.11.578	Primary	Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2).	2012 Jun 1	23275831
RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer.	2012 Oct 1	22846914
Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma.	2017 Feb 23	27841867

Patents

Sample Use Guides

In Vivo Use Guide

200 mpk/day once a day for 14 days.

Route of Administration: Intraperitoneal

In Vitro Use Guide

Treatment of MDA-MB-231 cells with RKI-1447 hampered their ability to form soft agar colonies with an IC50 value of 709 nM/L.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 12:12:26 GMT 2023` Edited by `admin` on `Sat Dec 16 12:12:26 GMT 2023`
Record UNII	F8GZ6C9MKZ
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

RKI-1447

Code

English

UREA, N-((3-HYDROXYPHENYL)METHYL)-N'-(4-(4-PYRIDINYL)-2-THIAZOLYL)-

Systematic Name

English

1-(3-HYDROXYBENZYL)-3-(4-(PYRIDIN-4-YL)THIAZOL-2-YL)UREA

Systematic Name

English

N-((3-HYDROXYPHENYL)METHYL)-N'-(4-(4-PYRIDINYL)-2-THIAZOLYL)UREA

Systematic Name

English

Code System Code Type Description

MESH

C576956