LY-364947 Property

Melting point:

>230℃ (dec.)

Boiling point:

490.8±45.0 °C(Predicted)

Density 

1.283±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: soluble2mg/mL, clear

pka

8.94±0.50(Predicted)

form 

powder

color 

white to beige

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.

InChIKey

IBCXZJCWDGCXQT-UHFFFAOYSA-N

Safety

Hazard Codes 

T,N

Risk Statements 

25-36/37/38-50/53

Safety Statements 

26-45-60-61

RIDADR 

UN 2811 6.1/PG 3

WGK Germany 

3

HS Code 

2933491090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H301Toxic if swalloed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

H400Very toxic to aquatic life

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P273Avoid release to the environment.

P301+P310IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

LY-364947 Chemical Properties,Usage,Production

Description

LY-364947 (396129-53-6) is a selective ALK5 inhibitor, IC50 = 59, 400 and 1400 nM for TGF-β RI, TGF-β RII and MLK-7K, respectively.1 Inhibits Smad2 phosphorylation induced by TGF-β as well as fibronectin expression and MDA-MB-231 cell invasion.2 LY-364947 abolishes resistance of glioblastoma-initiating cells to radiation.3?Cell permeable.

Uses

LY 364947, is a potent ATP-competitive inhibitor of Tgf-b signaling.

Definition

ChEBI: LY 364947 is a member of the class of pyrazoles carrying pyridin-2-yl and quinolin-4-yl substituents at positions 3 and 4 respectively. It has a role as a TGFbeta receptor antagonist. It is a member of pyrazoles, a member of pyridines and a member of quinolines.

Biological Activity

Selective inhibitor of TGF- β type-I receptor (TGF- β RI, TGFR-I, T β R-I, ALK-5) (IC 50 values are 59, 400 and 1400 nM for TGR- β RI, TGF- β RII and MLK-7K respectively). Inhibits TGF- β -dependent luciferase production in mink lung cells (p3TP lux) and growth in mouse fibroblasts (NIH 3T3) (IC 50 values are 47 and 89 nM respectively). Suppresses invasion of MDA-MB-231 breast cancer cells in a matrigel invasion assay.

Biochem/physiol Actions

LY-364947 is a selective, ATP-competitive inhibitor of Transforming Growth Factor-β Type I receptor kinase (TGF-β RI, ALK5) with IC50 = 59 nM. It is much less potent at related kinases, with IC50 = 400 nM for TGF-β RII and IC50 = 1400 nM for mixed lineage kinase-7 (MLK-7), a kinase in the MAP kinase signal pathway and closely related to TGF-β RII. LY-364947 inhibits TGF-β-dependent cellular growth (IC50 = 81 nM) in NIH 3T3 mouse fibroblasts.

in vitro

ly364947 was quickly identified as a potent inhibitor (ic50= 51 nm) and was chosen as a platform for sar development. compounds were further evaluated as inhibitors of tgf-β-dependent luciferase production in mink lung cells (p3tp lux) and growth in mouse fibroblasts (nih 3t3) [1].

in vivo

in a rat model of nmda-induced retinal degeneration, simultaneous injection of nmda and the tgf-β inhibitor ly364947 slightly but significantly attenuated the reduction in number of cells in the ganglion cell layer and almost completely prevented the enhancement of capillary degeneration. [3].

storage

Store at RT

References

1) Sawyer?et al. (2003),?Synthesis and activity of new aryl-and hetero-aryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain; J. Med. Chem.,?46?3953 2) Shiou?et al. (2006),?Smad4-dependent regulation of urokinase plasminogen activator secretion and RNA stability associated with invasiveness by autocrine and paracrine transforming growth factor-beta; J. Biol. Chem.,?281?33971 3) Hardee?et al. (2012),?Resistance of glioblastoma-initiating cells to radiation mediated by the tumor microenvironment can be abolished by inhibiting transforming growth factor-β; Cancer Res.,?72?4119