product name LY364947
Description: LY364947 (also known as 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 inhibits TGF- β -dependent luciferase production in mink lung cells (p3TP lux) and growth in mouse fibroblasts (NIH 3T3). LY364947 was chosen as a platform for SAR development. Compounds were further evaluated as inhibitors of TGF-β-dependent luciferase production in mink lung cells (p3TP Lux) and growth in mouse fibroblasts (NIH 3T3).
References: Biochemistry. 2005 Feb 22;44(7):2293-304; Blood. 2008 May 1;111(9):4571-9.
272.3
Formula
C17H12N4
CAS No.
396129-53-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 1 mg/mL (3.7 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
HTS 466284
other peoduct :
| In Vitro |
In vitro activity: 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. LY364947 (3 μM) induces expression of Prox1 and LYVE-1 in almost all HDLECs after 24 hours. 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. Kinase Assay: Cell Assay: |
|---|---|
| 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. LY364947 (25 mg /kg) increases p-Akt and decreases nuclear Foxo3a in leukaemia-initiating cells in CML-affected mice. |
| Animal model | Tumor xenograft models with BxPC3 pancreatic adenocarcinoma cells.aminonucleoside-induced renal fibrosis |
| Formulation & Dosage | Dissolved in 5 mg/mL in DMSO and diluted with 100 μL PBS; 1 mg/kg; i.p. administration |
| References | Biochemistry. 2005 Feb 22;44(7):2293-304; Blood. 2008 May 1;111(9):4571-9. |
