LY364947

Catalog No.S2805 Batch:S280502

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Technical Data

Formula

C17H12N4
Molecular Weight 272.3 CAS No. 396129-53-6
Solubility (25°C)* In vitro DMSO 20 mg/mL (73.44 mM)
Water Insoluble
Ethanol Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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]
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 Assay:

[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 Study:

[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.

Customer Product Validation

Data from [Chem Biol Interact, 2014, 217, 1-8]

Data from [Data independently produced by , , Nat Commun, 2016, 7:12047]

Data from [Data independently produced by , , Cancer Lett, 2017, 403:86-97]

Data from [Data independently produced by , , Int J Mol Med, 2016, 38(1):172-82]

Selleck's LY364947 has been cited by 52 publications

Automated, High-Throughput Phenotypic Screening and Analysis Platform to Study Pre- and Post-Implantation Morphogenesis in Stem Cell-Derived Embryo-Like Structures [ Adv Sci (Weinh), 2024, 11(4):e2304987] PubMed: 37991133
Genomic and transcriptomic profiling of peripheral T cell lymphoma reveals distinct molecular and microenvironment subtypes [ Cell Rep Med, 2024, 5(2):101416] PubMed: 38350451
PAX1 represses canonical Wnt signaling pathway and plays dual roles during endoderm differentiation [ Cell Commun Signal, 2024, 22(1):242] PubMed: 38664733
MHC-II presentation by oral Langerhans cells impacts intraepithelial Tc17 abundance and Candida albicans oral infection via CD4 T cells [ Front Oral Health, 2024, 5:1408255] PubMed: 38872986
Transcriptome-based chemical screens identify CDK8 as a common barrier in multiple cell reprogramming systems [ Cell Rep, 2023, 42(6):112566] PubMed: 37235474
A TGF-β-responsive enhancer regulates SRC expression and epithelial-mesenchymal transition-associated cell migration [ J Cell Sci, 2023, 136(15)jcs261001] PubMed: 37439249
A TGF-β-responsive enhancer regulates SRC expression and epithelial-mesenchymal transition-associated cell migration [ J Cell Sci, 2023, 136(15)jcs261001] PubMed: 37439249
Cancer apelin receptor suppresses vascular mimicry in malignant melanoma [ Pathol Oncol Res, 2023, 29:1610867] PubMed: 36776217
A proliferative to invasive switch is mediated by srGAP1 downregulation through the activation of TGF-β2 signaling [ Cell Rep, 2022, 40(12):111358] PubMed: 36130489
Gene silencing by EZH2 suppresses TGF-β activity within the decidua to avert pregnancy-adverse wound healing at the maternal-fetal interface [ Cell Rep, 2022, 38(5):110329] PubMed: 35108527

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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