LY364947

Catalog No.S2805

LY364947 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.

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LY364947 Chemical Structure

LY364947 Chemical Structure
Molecular Weight: 272.3

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Quality Control & MSDS

Related Compound Libraries

LY364947 is available in the following compound libraries:

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Product Information

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  • Research Area
  • Inhibition Profile
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description LY364947 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)
IC50 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]
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]
Features

Protocol(Only for 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.

Animal Study: [4]

Animal Models Tumor xenograft models with BxPC3 pancreatic adenocarcinoma cells.
Formulation Dissolved in 5 mg/mL in DMSO and diluted with 100 μL PBS
Dosages 1 mg/kg
Administration Intraperitoneally administrated 3 times a week for 3 weeks.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Li HY, et al. J Med Chem, 2006, 49(6), 2138-2142.

[2] Vogt J, et al. Cell Signal, 2011, 23(11), 1831-1842.

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Chemical Information

Download LY364947 SDF
Molecular Weight (MW) 272.3
Formula

C17H12N4

CAS No. 396129-53-6
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms HTS 466284
Solubility (25°C) * In vitro DMSO 1 mg/mL (3.67 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name Quinoline, 4-[3-(2-pyridinyl)-1H-pyrazol-4-yl]-

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.

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