Home TGF-beta/Smad TGF-beta/Smad inhibitor - RIP kinase inhibitor - Casein Kinase inhibitor - Mixed Lineage Kinase inhibitor LY364947 For research use only.

LY364947

Synonyms: HTS 466284

LY364947 (HTS 466284) is a potent ATP-competitive inhibitor of TGFβR-I with IC50 of 59 nM in a cell-free assay, shows 7-fold selectivity over TGFβR-II.

LY364947 Chemical Structure

LY364947 Chemical Structure

CAS No. 396129-53-6

Purity & Quality Control

LY364947 Related Products

Signaling Pathway

TGF-beta/Smad Signaling Pathways

TGF-beta/Smad Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
mink Mv1Lu lung cells Function assay Inhibition of TGFbeta R1 induced transcriptional activation of p3TP-Lux in mink Mv1Lu lung cells, IC50=0.04 μM 16539403
Sf9 cells Function assay Inhibition of human Transforming growth factor (TGF) beta-1 receptor (T204D mutation) autophosphorylation in Sf9 cells, IC50=0.051 μM 12954047
Sf9 cells Function assay Inhibition of recombinant human TGFbeta R1 expressed in Sf9 cells, IC50=0.059 μM 16539403
HepG2 cells Function assay Inhibition of TGF-beta-induced expression of PAI-luciferase reporter in HepG2 cells, IC50=0.06 μM 14643325
NIH3T3 cells Function assay Inhibitory activity against TGF-beta-stimulated proliferation in NIH3T3 cells, IC50=0.081 μM 16539403
Sf9 cells Function assay Inhibition of recombinant human TGFbeta R2 expressed in Sf9 cells, IC50=0.4 μM 16539403
Click to View More Cell Line Experimental Data

Biological Activity

Description LY364947 (HTS 466284) is a potent ATP-competitive inhibitor of TGFβR-I with IC50 of 59 nM in a cell-free assay, shows 7-fold selectivity over TGFβR-II.
Targets
TGFβRI [1]
(Cell-free assay)		 RIPK2 [2]
(Cell-free assay)		 CK1δ [2]
(Cell-free assay)		 TGFβRII [1]
(Cell-free assay)		 MLK-7K [1]
(Cell-free assay)
59 nM 0.11 μM 0.22 μM 0.4 μM 1.4 μM
In vitro
In vitro LY364947 is an ATP competitive and tight-binding inhibitor, inhibiting phosphorylation of P-Smad3 by TGFβR-I kinase with Ki of 28 nM. LY364947 inhibits in vivo Smad2 phosphorylation within the NMuMg cells with IC50 of 135 nM. LY364947 reverses TGF-β-mediated growth inhibition in NMuMg cells with IC50 of 0.218 μM. LY364947 potentiates the xVent2-lux BMP4 response in NMuMg cells by 30% at concentrations as low as 0.25 μM. LY364947 (2 μM) prevents TGF-β-induced epithelial−mesenchymal transition in NMuMg cells. [3] LY364947 (3 μM) induces expression of Prox1 and LYVE-1 in almost all HDLECs after 24 hours. [4] LY364947 promotes nuclear export of Foxo3a, with low Smad2/3 and high Akt phosphorylation levels in leukaemia-initiating cells. LY364947 (< 20 μM) suppresses leukaemia-initiating cells colony-forming ability after co-culture with OP-9 stromal cells. [5]
Kinase Assay Filter-binding assay
The IC50 of LY364947 at different enzyme concentrations are 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 are incubated at 30 °C for 30 min. The IC50 is calculated using a nonlinear regression method with GraphPad Prism software. The binding type is determined by plotting the correlation between enzyme concentrations and IC50 values.
Cell Research Cell lines HOXB9-MCF10A cells
Concentrations 10 μM
Incubation Time 24 h
Method

HOXB9-MCF10A cells were treated with 10 μM LY364947 for 24 h. Proteins were analyzed for phospho-Smad2 and total Smad2 levels
Experimental Result Images Methods Biomarkers Images PMID
Western blot FOXC2 / p-Smad / Smad / p-p38 / p38 / p-ATF2 / ATF2 26804168
Immunofluorescence TEEB 31387632
In Vivo
In vivo LY364947 (1 mg/kg i.p.) accelerates lymphangiogenesis, as evidence by significantly increased the LYVE-1-positive areas, in a mouse model of chronic peritonitis. LY364947 (1 mg/kg i.p.) significantly increases the LYVE-1-positive areas in tumor tissues in tumor xenograft models using BxPC3 pancreatic adenocarcinoma cells. [4] LY364947 (25 mg /kg) increases p-Akt and decreases nuclear Foxo3a in leukaemia-initiating cells in CML-affected mice. [5]
Animal Research Animal Models Tumor xenograft models with BxPC3 pancreatic adenocarcinoma cells.
Dosages 1 mg/kg
Administration Intraperitoneally administrated 3 times a week for 3 weeks.

Chemical Information & Solubility

Molecular Weight 272.3 Formula

C17H12N4
CAS No. 396129-53-6 SDF Download LY364947 SDF
Smiles C1=CC=C2C(=C1)C(=CC=N2)C3=C(NN=C3)C4=CC=CC=N4
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 4 mg/mL ( (14.68 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy LY364947 | LY364947 supplier | purchase LY364947 | LY364947 cost | LY364947 manufacturer | order LY364947 | LY364947 distributor