Home >> LY364947
Related Products
LY364947 inhibitor of TGF-β type I receptor kinase domain

Catalog No.B2287
Size Price Stock Qty
10mM (in 1mL DMSO)
$81.00
In stock
10mg
$77.00
In stock
25mg
$189.00
In stock
50mg
$259.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

      

Sample solution is provided at 25 µL, 10mM.

Product Citations

1. Lin B, Coleman JH, et al. "Injury Induces Endogenous Reprogramming and Dedifferentiation of Neuronal Progenitors to Multipotency." Cell Stem Cell. 2017 Nov 20. pii: S1934-5909(17)30375-2. PMID:29174332

Quality Control

Chemical structure

LY364947

Related Biological Data

LY364947

Protocol

Kinase experiment [1]:

Filter-binding assay

The IC50 values of LY364947 at different enzyme concentrations were determined by the filter-binding assay. Typically, 40 μL reactions in 50 mM HEPES at pH 7.5, 1 mM NaF, 200 μM pKSmad3(-3) and 50 mM ATP containing a titration of each inhibitor with concentrations of 1600, 800, 400, 200, 100, 50, 25, and 0 nM were incubated at 30 °C for 30 mins. The IC50 values were calculated using a nonlinear regression method with GraphPad Prism software. The binding type was determined by plotting the correlation between enzyme concentrations and IC50 values.

Cell experiment [2]:

Cell lines

HOXB9-MCF10A cells

Preparation method

The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

10 μM; 24 hrs

Applications

In HOXB9-MCF10A cells, LY364947 suppressed Smad2 phosphorylation by inhibiting TGF-β activation, meanwhile, without affecting the expression of TGF-β1 and TGF-β2. Besides, LY364947 induced epithelial morphological changes, with re-expression of E-cadherin as well as suppression of fibronectin and vimentin. In addition, LY364947 reduced migration and invasiveness of HOXB9-MCF10A cells.

Animal experiment [3]:

Animal models

A rat model of NMDA-induced retinal degeneration

Dosage form

50 nM; 5μL; intravitreal injection

Applications

In a rat model of NMDA-induced retinal degeneration, LY364947 significantly suppressed cell loss in the ganglion cell layer induced by NMDA. Besides, LY364947 markedly prevent vascular damage in the injured retina caused by NMDA. In addition, co-treatment with NMDA and LY364947 did not cause any morphological change of NG2-positive pericytes.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Peng SB, Yan L, Xia X, Watkins SA, Brooks HB, Beight D, Herron DK, Jones ML, Lampe JW, McMillen WT, Mort N, Sawyer JS, Yingling JM. Kinetic characterization of novel pyrazole TGF-beta receptor I kinase inhibitors and their blockade of the epithelial-mesenchymal transition. Biochemistry. 2005 Feb 22;44(7):2293-304.

[2]. Hayashida T, Takahashi F, Chiba N, Brachtel E, Takahashi M, Godin-Heymann N, Gross KW, Vivanco Md, Wijendran V, Shioda T, Sgroi D, Donahoe PK, Maheswaran S. HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1100-5.

[3]. Ueda K, Nakahara T, Mori A, Sakamoto K, Ishii K. Protective effects of TGF-β inhibitors in a rat model of NMDA-induced retinal degeneration. Eur J Pharmacol. 2013 Jan 15;699(1-3):188-93.

LY364947 Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

LY364947 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Chemical Properties

Cas No. 396129-53-6 SDF Download SDF
Chemical Name 4-(5-pyridin-2-yl-1H-pyrazol-4-yl)quinoline
Canonical SMILES C1=CC=C2C(=C1)C(=CC=N2)C3=C(NN=C3)C4=CC=CC=N4
Formula C17H12N4 M.Wt 272.3
Solubility ≥24.4mg/ml in DMSO Storage Store at -20°C
Shipping Condition Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Background

The multifunctional cytokine transforming growth factor-β (TGF-β) is a member of a large family of growth factors involved in the regulation of a diverse array of biological processes including cell growth and differentiation, matrix modulation, and embryonic development. LY364947 is a inhibitor of the transforming growth factor-β type I receptor kinase domain.

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].

Clinical trial: Up to now, LY364947 is still in the preclinical development stage.

Reference:
[1] Sawyer JS, Anderson BD, Beight DW, Campbell RM, Jones ML, Herron DK, Lampe JW, McCowan JR, McMillen WT, Mort N, Parsons S, Smith EC, Vieth M, Weir LC, Yan L, Zhang F, Yingling JM.  Synthesis and activity of new aryl- and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain. J Med Chem. 2003 Sep 11;46(19):3953-6.
[2] Ueda K, Nakahara T, Mori A, Sakamoto K, Ishii K.  Protective effects of TGF-β inhibitors in a rat model of NMDA-induced retinal degeneration. Eur J Pharmacol. 2013 Jan 15;699(1-3):188-93.