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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C18H14N6O2 |
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分子量 | 346.34 | CAS No. | 677297-51-7 | ||||
Solubility (25°C)* | 体外 | DMSO | 9 mg/mL (25.98 mM) | ||||
Water | Insoluble | ||||||
Ethanol | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | TG100-115 is a PI3Kγ/δ inhibitor with IC50 of 83 nM/235 nM, with little effect on PI3Kα/β. Phase 1/2. |
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in vitro | TG100-115 inhibits PI3Kγ and -δ, with IC50 of 83 and 235 nM, respectively. TG100-115 is not active for PI3Kα and -β, with IC50 of 1.2 and 1.3 mM. In human umbilical vein endothelial cells (HUVECs), TG100-115 (up to 10 μM) has no effects on cell proliferation and VEGF-stimulated ERK phosphorylation. However, TG100-115 (10 μM) interrupts other VEGF signaling pathways, such as those that culminate in VE-cadherin phosphorylation. [1] In HUVECs, TG100-115 (10 μM) 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 μM) 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 PI3Kγ/δ to induce VP. [3] In a mouse asthma model, aerosolized TG100-115 markedly reduces the pulmonary eosinophilia, inhibits interleukin-13 and mucin accumulation. [4] |
特徴 | A potent and dual selective PI3Kγ/δ inhibitor. |
キナーゼアッセイ | PI3K assays | |
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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. | ||
細胞アッセイ | 細胞株 | Human umbilical vein endothelial cells (HUVECs) |
濃度 | 10 μM, dissolved in DMSO as stock solution | |
反応時間 | 24, 48, and 72 hours | |
実験の流れ | Cells plated in 96-well cluster plates (5 × 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 late | |
動物実験 | 動物モデル | Rat (Sprague-Dawley) myocardial ischemia (MI) model |
投薬量 | 0.5-5 mg/kg | |
投与方法 | By intravenous injection. |
, , Saraswati Sukumar of Johns Hopkins University School of Medicine
Data from [Data independently produced by , , Biochim Biophys Acta, 2017, 1861(4):947-957]
Inactivation of TRPM7 Kinase Targets AKT Signaling and Cyclooxygenase-2 Expression in Human CML Cells [ Function (Oxf), 2023, 4(6):zqad053] | PubMed: 37786778 |
The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics [ Elife, 2021, 10e68544] | PubMed: 34766907 |
The FBW7-MCL-1 Axis Is Key in M1 and M2 Macrophage-Related Colon Cancer Cell Progression: Validating the Immunotherapeutic Value of Targeting PI3Kγ [ Exp Mol Med, 2020, 22] | PubMed: 32444799 |
Simultaneous Control of Endogenous and User-Defined Genetic Pathways Using Unique ecDHFR Pharmacological Chaperones. [ Cell Chem Biol, 2020, 24 pii: S2451-9456(20)30080-5] | PubMed: 32330442 |
TRPM7 Kinase Is Essential for Neutrophil Recruitment and Function via Regulation of Akt/mTOR Signaling [ Front Immunol, 2020, 11:606893] | PubMed: 33658993 |
A facile and sensitive method of quantifying glutaminase binding to its inhibitor CB-839 in tissues [ J Genet Genomics, 2020, 47(7):389-395] | PubMed: 33004309 |
Suppression of TRPM7 Enhances TRAIL-induced Apoptosis in Triple-Negative Breast Cancer Cells [ J Cell Physiol, 2020, 29] | PubMed: 32468675 |
Inhibition of transient receptor potential melastatin 7 (TRPM7) protects against Schwann cell trans-dedifferentiation and proliferation during Wallerian degeneration [ Anim Cells Syst (Seoul), 2020, 24(4):189-196] | PubMed: 33029295 |
PI3Kgamma Inhibitor Attenuates Immunosuppressive Effect of Poly(l-Glutamic Acid)-Combretastatin A4 Conjugate in Metastatic Breast Cancer. [ Adv Sci (Weinh), 2019, 6(12):1900327] | PubMed: 31380170 |
Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells [ Int J Oncol, 2018, 52(3):828-840] | PubMed: 29344641 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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