| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
LY2109761 (LY-2109761; LY 2109761) is a novel, orally bioavailable and selective dual inhibitor of transforming growth factor beta receptor I/II (TGF-β receptor type I/II: TβRI/II) with potential antitumor activity. It inhibits TGF-β receptor type I/II with Ki values of 38 nM and 300 nM in a cell-free assay, respectively; LY2109761 was shown to be able to negatively affect the phosphorylation of Smad2. In vivo, LY2109761, in combination with gemcitabine, significantly reduced the tumor burden, prolonged survival, and reduced spontaneous abdominal metastases. The efficacy of LY2109761 on tumor growth, survival, and reduction of spontaneous metastasis have been evaluated in an orthotopic murine model of metastatic pancreatic cancer expressing both luciferase and green fluorescence proteins.
| ln Vitro |
The growth of L3.6pl/GLT soft agar colonies was considerably decreased by LY2109761 in a dose-dependent manner. The inhibition was around 33% at 2 μM and 73% at 20 μM. TGF-β1-stimulated migration of L3.6pl/GLT cells was almost entirely reduced when TβRI/II kinase activity was targeted with LY2109761 (5 μM) [1]. A dose-dependent reduction in Smad-2 phosphorylation is induced by LY2109761. LY2109761 prevents Smad-2's endogenous phosphorylation by HLE. Via a three-dimensional structure, LY2109761 prevents the invasion of HLE and HLF as well as the movement of certain ECM proteins. E-cadherin mRNA expression is increased by LY2109761 after 24 hours, and protein levels are increased after 48 hours [2]. Following radiation exposure, LY2109761 pretreatment decreased clonogenic survival in T98 and U87MG cell cultures, leading to higher radiosensitivity with DEF0.1 values of 1.30 and 1.37, respectively [3].
|
||
|---|---|---|---|
| ln Vivo |
By reducing tumor volume significantly, LY2109761 (50 mg/kg, po) increased mice's median survival time to 45.0 days. The GFP signal showed that mice treated with LY2109761 acquired considerably fewer metastatic lesions, and in some of them, no metastatic lesions were detected in the abdomen [1]. Enhancement of radiation-induced tumor development delay in the subcutaneous xenograft tumor model of BALB/c nude mice U87MG is achieved by LY2109761. Radiation therapy's anti-tumor efficacy is enhanced and the survival rate of orthotopic CSLC glioblastoma models is improved by LY2109761 [2].
|
||
| Animal Protocol |
|
||
| References |
[1]. Melisi D, et al. LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis. Mol Cancer Ther, 2008, 7(4), 829-840.
[2]. Fransvea E, et al. Blocking transforming growth factor-beta up-regulates E-cadherin and reduces migration and invasion of hepatocellular carcinoma cells. Hepatology, 2008, 47(5), 1557-1566. [3]. Zhang M, et al. Blockade of TGF-β signaling by the TGFβR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma. Cancer Res, 2011, 71(23), 7155-7167 |
| Molecular Formula |
C26H27N5O2
|
|
|---|---|---|
| Molecular Weight |
441.52
|
|
| CAS # |
700874-71-1
|
|
| Related CAS # |
|
|
| SMILES |
O1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])OC2C([H])=C([H])C3C(C=2[H])=NC([H])=C([H])C=3C2C(C3=C([H])C([H])=C([H])C([H])=N3)=NN3C([H])([H])C([H])([H])C([H])([H])C3=2)C([H])([H])C1([H])[H]
|
|
| Synonyms |
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2649 mL | 11.3245 mL | 22.6490 mL | |
| 5 mM | 0.4530 mL | 2.2649 mL | 4.5298 mL | |
| 10 mM | 0.2265 mL | 1.1325 mL | 2.2649 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.
|
|---|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
