ArtNr |
S1352-10000 |
Hersteller |
Selleckchem
|
CAS-Nr. |
677297-51-7 |
Menge |
10 g |
Kategorie |
|
Typ |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
677297-51-7' |
Similar products |
TG100-115 |
Lieferbar |
|
Administration |
By intravenous injection. |
Animal Models |
Rat (Sprague-Dawley) myocardial ischemia (MI) model |
Cell lines |
Human umbilical vein endothelial cells (HUVECs) |
Chemical Name |
6, 7-Bis(3-hydroxyphenyl)pteridine-2, 4-diamine |
Clinical Trials |
TG100-115 is currently under a Phase I/II clinical trial in myocardial infarction. |
Concentrations |
10 uM, dissolved in DMSO as stock solution |
Description |
TG100-115 is a potent and dual selective inhibitor for PI3Kgamma and PI3Kdelta with IC50 of 83 nM and 235 nM, respectively. |
Dosages |
0.5–5 mg/kg |
Features |
TG100-115 is a potent and dual selective PI3Kgamma/delta inhibitor. |
Formulation |
Dissolved in PEG or sulfobutyl ether beta-cyclodextrin |
IC50 |
83 nM, 83 nM, 83 nM, 83 nM, 83 nM, 83 nM |
In vitro |
TG100-115 inhibits PI3Kgamma and -delta, with IC50 of 83 and 235 nM, respectively. TG100-115 is not active for PI3Kalpha and -beta, with IC50 of 1.2 and 1.3 mM. In human umbilical vein endothelial cells (HUVECs), TG100-115 (up to 10 uM) has no effects on cell proliferation and VEGF-stimulated ERK phosphorylation. However, TG100-115 (10 uM) interrupts other VEGF signaling pathways, such as those that culminate in VE-cadherin phosphorylation. [1] In HUVECs, TG100-115 (10 uM) inhibits the VEGF-induced increase of total level of VE-cadherin. TG100-115 inhibits VEGF mediated phosphorylation of mTOR and p70S6 kinase, both of which are downstream of PI3K. TG100-115 (125 nM to 10 uM) also inhibits FGF-stimulated phosphorylation of Akt. [2] |
In vivo |
In Miles assay models, TG100-115 (1–5 mg/kg) reduces edema formation and inflammation in rats. In rigorous rodent and porcine models of myocardial ischemia (MI), TG100-115 (0.5–5 mg/kg) provides potent cardioprotection, limits infarct development, and preserves myocardial function. [1] In mice, TG100-115 (5 mg/kg) markedly diminishes vascular permeability (VP) in response to either Sema3A or VEGF, indicating that both factors may depend on PI3Kgamma/delta to induce VP. [3] In a mouse asthma model, aerosolized TG100-115 markedly reduces the pulmonary eosinophilia, inhibits interleukin-13 and mucin accumulation. [4] |
Incubation Time |
24, 48, and 72 hours |
Kinase Assay |
PI3K assays, Forty mL of reaction buffer (20 mM Tris/4 mM MgCl2/10 mM NaCl, pH 7.4) containing 50 mM D-myo-phosphatidylinositol 4, 5-bisphosphate substrate and the desired PI3K isoform are aliquoted to 96-well plates, kinase concentrations are 250-500 ng/well, such that linear kinetics are achieved over 90 min. TG100-115 is then added as 2.5 mL of a DMSO stock to final concentration range of 100 mM to 1 nM. Reactions are initiated by addition of 10 mL of ATP to a final concentration of 3 mM, and after 90 min, 50 mL of Kinase-Glo reagent added to quantify residual ATP levels, luminosity is measured using an Ultra 384 instrument. Control reactions omitting either TG100-115 or substrate are also performed. IC50 values are derived from experimental data by nonlinear curve fitting using Prism Version 4. |
Method |
Cells plated in 96-well cluster plates (5 x 103 cells/well) are cultured in assay medium (containing 0.5% serum and 50 ng/ml VEGF) in the presence or absence of TG100-115, and cell numbers are quantified by XTT assay 24, 48, or 72 hours later. |
Molecular Weight (MW) |
346, 34 |
Picture ChemicalStructure Description |
TG100-115 Chemical Structure |
Picture Description 1 |
, , Saraswati Sukumar of Johns Hopkins University School of Medicine, TG100-115purchased from Selleck, We treated all of drugs in T47D which has a PI3KCA H1044R mutation with the concentration shown below for 1 hour and performed western blot analysis using antibodies to phospho-AKT(SERINE 472), and total AKT. |
Solubility (25C) |
DMSO 9 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
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