| Name | LY-364947 |
| Description | LY-364947 (HTS466284) is a potent ATP-competitive inhibitor of TGFβR-I. |
| Kinase Assay | The IC50 of LY-364947 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. |
| In vitro | Administering 1 mg/kg i.p. of LY364947 significantly enhances the LYVE-1-positive regions within the tumor tissues in a BxPC3 pancreatic cancer xenograft model. Similarly, 25 mg/kg i.p. of LY364947 markedly increases LYVE-1-positive areas in a chronic peritonitis mouse model, indicating accelerated lymphangiogenesis. Additionally, LY364947 (25 mg/kg) increases p-Akt levels and decreases nuclear Foxo3a in leukemia-initiating cells in mice infected with CML. |
| In vivo | At a concentration as low as 0.25 μM, LY364947 enhances the xVent2-lux BMP4 response in NMuMG cells by 30%. At 2 μM, it prevents TGF-β-induced epithelial-mesenchymal transition (EMT) in NMuMG cells. A 3 μM dose of LY364947, after 24 hours of treatment, induces the expression of Prox1 and LYVE-1 in nearly all HDLECs. LY364947 promotes the nuclear export of Foxo3a and is characterized by low Smad2/3 and high Akt phosphorylation levels in leukemia-positive cells. When co-cultured with OP-9 stromal cells, LY364947 (at concentrations <20 μM) inhibits the colony-forming ability of leukemia-initiating cells. Acting as an ATP-competitive, tight-binding inhibitor, LY364947 inhibits P-Smad3 phosphorylation through TGFβR-I kinase with a Ki of 28 nM and inhibits Smad2 phosphorylation in NMuMG cells in vivo with an IC50 of 135 nM. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | DMSO : 15.625 mg/mL (57.38 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 1 mg/mL (3.67 mM), Sonication is recommended.
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| Keywords | Transforming growth factor beta receptors | TGFβRII | TGFβRI | TGF-β/Smad | TGF-β Receptor | TGFβ | TGFbeta/Smad | TGF-beta | TGFbeta | TGF-b/Smad | TGFb | Smad | RIPkinase | RIPK2 | RIP kinase | MLK-7K | LY-364947 | LY364947 | Inhibitor | inhibit | HTS-466284 | HTS 466284 | CK1δ | CaseinKinase | Casein Kinase |
| Inhibitors Related | Melamine | SB-431542 | Ellagic acid | Casein | Oditrasertib | Hydrochlorothiazide | Pirfenidone | A 83-01 | Cetrimonium bromide | Galunisertib | Alantolactone | LY294002 |
| Related Compound Libraries | Bioactive Compound Library | Pain-Related Compound Library | Membrane Protein-targeted Compound Library | Kinase Inhibitor Library | Pyroptosis Compound Library | Inhibitor Library | Immunology/Inflammation Compound Library | Anti-Aging Compound Library | Bioactive Compounds Library Max | Anti-Metabolism Disease Compound Library | TGF-beta/Smad Compound Library | Neuronal Differentiation Compound Library |
United States
