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LY-364947

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LY-364947 Basic information

Product Name:
LY-364947
Synonyms:
  • [3-(Pyridin-2-yl)-4-(4-quinonyl)]-1H-pyrazole
  • 4-[3-(2-Pyridinyl)-1H-pyrazol-4-yl]-quinoline
  • LY364947(HTS 466284)
  • E 616451
  • HTS 466284
  • 2-[4-(Quinolin-4-yl)-1H-pyrazol-3-yl]pyridine, 3-(Pyridin-2-yl)-4-(quinolin-4-yl)-1H-pyrazole
  • Quinoline, 4-[3-(2-pyridinyl)-1H-pyrazol-4-yl]-
  • 4-[3-(2-Pyridinyl)-1H-pyrazol-4-yl]quinoline E 616451
CAS:
396129-53-6
MF:
C17H12N4
MW:
272.3
Product Categories:
  • API
  • Inhibitors
  • Smad
  • TGF-beta
Mol File:
396129-53-6.mol
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LY-364947 Chemical Properties

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
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Safety Information

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
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LY-364947 Usage And Synthesis

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

LY-364947Supplier

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