TG100-115

Catalog No.S1352 Batch:S135201

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Technical Data

Formula

C18H14N6O2
Molecular Weight 346.34 CAS No. 677297-51-7
Solubility (25°C)* In vitro DMSO 9 mg/mL (25.98 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 30%PEG300 65%ddH2O
0.4mg/ml Taking the 1 mL working solution as an example, add 50 μL of 8 mg/ml clarified DMSO stock solution to 300 μL of PEG 300, mix evenly to clarify it; then continue to add 650 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description TG100-115 is a PI3Kγ/δ inhibitor with IC50 of 83 nM/235 nM, with little effect on PI3Kα/β. Phase 1/2.
Targets
PI3Kγ [1]
(Cell-free assay)		 PI3Kδ [1]
(Cell-free assay)		 PI3Kβ [1]
(Cell-free assay)		 PI3Kα [1]
(Cell-free assay)
83 nM 235 nM 1.2 μM 1.3 μM
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]
Features A potent and dual selective PI3Kγ/δ inhibitor.

Protocol (from reference)

Kinase Assay:[1]
  • 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.
Cell Assay:[1]
  • Cell lines

    Human umbilical vein endothelial cells (HUVECs)

  • Concentrations

    10 μM, dissolved in DMSO as stock solution

  • Incubation Time

    24, 48, and 72 hours

  • Method

    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
Animal Study:[1]
  • Animal Models

    Rat (Sprague-Dawley) myocardial ischemia (MI) model

  • Dosages

    0.5-5 mg/kg

  • Administration

    By intravenous injection.

Customer Product Validation

, , Saraswati Sukumar of Johns Hopkins University School of Medicine

Data from [Data independently produced by , , Biochim Biophys Acta, 2017, 1861(4):947-957]

Selleck's TG100-115 has been cited by 14 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.