| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
LY364947 (also known as HTS-466284; LY 364947; HTS466284; LY-364947) is a potent, selective and ATP-competitive inhibitor of TGFβR-I with potential antineoplastic activity. It inhibits TGFβR-I with an IC50 of 59 nM in a cell-free assay, and exhibits 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).
| ln Vitro |
LY-364947 is an ATP competitive tight-binding inhibitor that, at a Ki of 28 nM, prevents P-Smad3 from being phosphorylated by TGFβR-I kinase. In NMuMg cells, LY-364947 inhibits Smad2 phosphorylation in vivo at an IC50 of 135 nM. In NMuMg cells, LY-364947 reverses TGF-β-mediated growth inhibition with an IC50 of 0.218 μM. In NMuMg cells, LY-364947 increases the xVent2-lux BMP4 response by 30% at as low as 0.25 μM. TGF-β-induced epithelial-to-mesenchymal transition in NMuMg cells is inhibited by LY-364947 (2 μM) [1]. Prox1 and LYVE-1 expression was induced in nearly all HDLECs by LY-364947 (3 μM) after a 24-hour period [2]. When leukemia-initiating cells have high Akt phosphorylation levels and low Smad2/3, LY-364947 stimulates Foxo3a's nuclear export. Following co-cultivation with OP-9 stromal cells, leukemia-initiating cells' capacity to form colonies is inhibited by LY-364947 (< 20 μM) [3].
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| ln Vivo |
In a mouse model of chronic peritonitis, LY-364947 (1 mg/kg, ip) significantly increased the LYVE-1-positive region, indicating that it promotes lymphangiogenesis. Using BxPC3 pancreatic cancer cells as a tumor xenograft model, LY-364947 (1 mg/kg, i.p.) dramatically enhanced the amount of LYVE-1-positive tissue in the tumor [2]. In CML-affected mice, LY-364947 (25 mg/kg) raises p-Akt and lowers nuclear Foxo3a in leukemia-initiating cells [3].
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| Animal Protocol |
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| References |
[1]. Peng SB, et al. Kinetic characterization of novel pyrazole TGF-beta receptor I kinase inhibitors and their blockade of the epithelial-mesenchymal transition. Biochemistry, 2005, 44(7), 2293-2304.
[2]. Oka M, et al. Inhibition of endogenous TGF-beta signaling enhances lymphangiogenesis. Blood, 2008, 111(9), 4571-4579. [3]. Naka K, et al. TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature, 2010, 463(7281), 676-680 |
| Molecular Formula |
C17H12N4
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| Molecular Weight |
272.3
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| CAS # |
396129-53-6
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| Related CAS # |
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| SMILES |
N1([H])C(C2=C([H])C([H])=C([H])C([H])=N2)=C(C([H])=N1)C1=C([H])C([H])=NC2=C([H])C([H])=C([H])C([H])=C12
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| InChi Key |
IBCXZJCWDGCXQT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H12N4/c1-2-6-15-13(5-1)12(8-10-19-15)14-11-20-21-17(14)16-7-3-4-9-18-16/h1-11H,(H,20,21)
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| Chemical Name |
4-(3-(pyridin-2-yl)-1H-pyrazol-4-yl)quinoline
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (4.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (4.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6724 mL | 18.3621 mL | 36.7242 mL | |
| 5 mM | 0.7345 mL | 3.6724 mL | 7.3448 mL | |
| 10 mM | 0.3672 mL | 1.8362 mL | 3.6724 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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