LY364947

Catalog No.S2805 Synonyms: HTS 466284

For research use only.

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

CAS No. 396129-53-6

Selleck's LY364947 has been cited by 39 publications

Purity & Quality Control

Choose Selective TGF-beta/Smad Inhibitors

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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

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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
mink Mv1Lu lung cells NWLqNpZRTnWwY4Tpc44h[XO|YYm= MnnqTY5pcWKrdHnvckBw\iCWR1\i[ZRiKFJzIHnu[JVk\WRidILhcpNkemmydHnvcoFtKGGldHn2ZZRqd25ib3[gdFNVWC2OdYigbY4hdWmwazDNelFNfSCudX7nJINmdGy|LDDJR|UxRTBwMESg{txO M4j3flE3PTN7NECz
Sf9 cells NFzmco1HfW6ldHnvckBie3OjeR?= MkjiTY5pcWKrdHnvckBw\iCqdX3hckBVemGwc3\vdo1qdmdiZ4Lve5RpKG[jY4TvdkApXEeIKTDi[ZRiNTFicnXj[ZB1d3JiKGSyNFRFKG23dHH0bY9vMSCjdYTvdIhwe3Cqb4L5cIF1cW:wIHnuJHNnQSClZXzsd{whUUN3ME2wMlA2OSEQvF2= MnLXNVI6PTRyNEe=
Sf9 cells NEn5N2ZHfW6ldHnvckBie3OjeR?= NF[0eHFKdmirYnn0bY9vKG:oIILlZ49u[mmwYX70JIh2dWGwIGTHSoJmfGFiUkGg[ZhxemW|c3XkJIlvKFOoOTDj[YxteyxiSVO1NF0xNjB3OTFOwG0> M2\zbVE3PTN7NECz
HepG2 cells Ml3XSpVv[3Srb36gZZN{[Xl? M3XrXGlvcGmkaYTpc44hd2ZiVFfGMYJmfGFvaX7keYNm\CCneIDy[ZN{cW:wIH;mJHBCUS2udXPp[oVz[XOnIILldI9zfGW{IHnuJGhmeEd{IHPlcIx{NCCLQ{WwQVAvODZizszN MY[xOFY1OzN{NR?=
NIH3T3 cells M1izPGZ2dmO2aX;uJIF{e2G7 MmT1TY5pcWKrdH;yfUBi[3Srdnn0fUBi\2GrboP0JHRITi2kZYThMZN1cW23bHH0[YQheHKxbHnm[ZJifGmxbjDpckBPUUh|VEOgZ4VtdHNuIFnDOVA:OC5yOEGg{txO MUWxOlU{QTRyMx?=
Sf9 cells NH7MeGZHfW6ldHnvckBie3OjeR?= NWnxVmJzUW6qaXLpeIlwdiCxZjDy[YNwdWKrbnHueEBpfW2jbjDUS2Zj\XSjIGKyJIV5eHKnc4Pl[EBqdiCVZkmgZ4VtdHNuIFnDOVA:OC52IN88US=> NUm4XWR2OTZ3M{m0NFM>
Assay
Methods Test Index PMID
Western blot FOXC2 / p-Smad / Smad / p-p38 / p38 / p-ATF2 / ATF2 26804168
Immunofluorescence TEEB 31387632
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]

Protocol (from reference)

Kinase Assay:

[3]

  • 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:

[6]

  • 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

Animal Research:

[4]

  • Animal Models: Tumor xenograft models with BxPC3 pancreatic adenocarcinoma cells.
  • Dosages: 1 mg/kg
  • Administration: Intraperitoneally administrated 3 times a week for 3 weeks.

Solubility (25°C)

In vitro

DMSO 1 mg/mL
(3.67 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
4% DMSO+30% PEG 300+ddH2O
For best results, use promptly after mixing.

0.75mg/mL

Chemical Information

Molecular Weight 272.3
Formula

C17H12N4

CAS No. 396129-53-6
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1=CC=C2C(=C1)C(=CC=N2)C3=C(NN=C3)C4=CC=CC=N4

In vivo Formulation Calculator (Clear solution)

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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.

Molarity Calculator

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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

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