1. Apoptosis
  2. TNF Receptor
    Apoptosis
  3. TIC10

TIC10 (Synonyms: ONC-201)

Cat. No.: HY-15615A Purity: 99.80%
Handling Instructions

TIC10 is a potent, orally active, and stable tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) inducer which acts by inhibiting Akt and ERK, consequently activating Foxo3a and significantly inducing cell surface TRAIL. TIC10 can cross the blood-brain barrier.

For research use only. We do not sell to patients.

TIC10 Chemical Structure

TIC10 Chemical Structure

CAS No. : 1616632-77-9

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10 mM * 1 mL in DMSO USD 55 In-stock
Estimated Time of Arrival: December 31
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Estimated Time of Arrival: December 31
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50 mg USD 140 In-stock
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100 mg USD 220 In-stock
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200 mg USD 350 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Based on 3 publication(s) in Google Scholar

Other Forms of TIC10:

Top Publications Citing Use of Products

    TIC10 purchased from MCE. Usage Cited in: Oncotarget. 2018 Jan 10;9(15):12020-12034.

    WB detection of the total and phosphorylated ERK1/2, LC3B, p62, ATG5, ATG7 levels in the PC9/GR and HCC827/GR cells cultured in the four treatment conditions. 20 μM TIC10 treatment decreases the expression of LC3B-II, but increases the expression of p62 in both cells.
    • Biological Activity

    • Protocol

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    • References

    • Customer Review

    Description

    TIC10 is a potent, orally active, and stable tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) inducer which acts by inhibiting Akt and ERK, consequently activating Foxo3a and significantly inducing cell surface TRAIL. TIC10 can cross the blood-brain barrier.

    IC50 & Target[1]

    TRAIL

     

    In Vitro

    TIC10 transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier[1].
    TIC10 induces a sustained up-regulation of TRAIL in tumors and normal cells that may contribute to the demonstrable antitumor activity of TIC10[1].
    TIC10 inactivates kinases Akt and extracellular signal-regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription[1].
    TIC10 is an efficacious antitumor therapeutic agent that acts on tumor cells and their micro-environment to enhance the concentrations of the endogenous tumor suppressor TRAIL[1].
    TIC10 also causes a down-regulation of the total expression of ERK[1].

    In Vivo

    In DLD-1 colon cancer xenografts, TIC10 induces tumor stasis at 1 week after treatment, whereas TRAIL-treated tumors progress after a single dose. A single dose of TIC10 also induces a sustained regression of the SW480 xenograft and is equally effective when delivered by intraperitoneal or oral route, suggesting favorable oral bioavailability for TIC10. Titration of a single oral dose of TIC10 in the HCT116 xenograft model reveals sustained antitumor efficacy at 25 mg/kg. Exposure to oral TIC10 at 25 mg/kg weekly for 4 weeks in immunocompetent mice does not cause any changes in selected serum chemistry markers. The same oral dosing schedule is applied to Eμ-myc transgenic mice, which spontaneously develop meta-static lymphoma from weeks 9 to 12 of age, and TIC10 significantly (P=0.00789) prolongs the survival of these mice by 4 weeks[1].

    Clinical Trial
    Molecular Weight

    386.49

    Formula

    C₂₄H₂₆N₄O

    CAS No.

    1616632-77-9

    SMILES

    O=C1N(CC2=CC=CC=C2C)C3=NCCN3C4=C1CN(CC5=CC=CC=C5)CC4

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 31.25 mg/mL (80.86 mM; Need ultrasonic)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.5874 mL 12.9369 mL 25.8739 mL
    5 mM 0.5175 mL 2.5874 mL 5.1748 mL
    10 mM 0.2587 mL 1.2937 mL 2.5874 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (6.47 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: ≥ 2.5 mg/mL (6.47 mM); Clear solution

    • 3.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.5 mg/mL (6.47 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Cell Assay
    [1]

    Floating and adherent cells are analyzed on a Coulter-Beckman Elite Epics cytometer. For surface TRAIL experiments, adherent cells are harvested by brief trypsinization, fixed in 4% paraformaldehyde in phosphate-buffered saline (PBS) for 20 min, incubated with an anti-TRAIL antibody at 1:250 overnight, washed and incubated with anti-rabbit Alexa Fluor 488 for 30 min, and analyzed. Cells are gated on forward and side scatter to eliminate debris and dead cells from the analysis. Surface TRAIL data are expressed as median fluorescence intensity relative to that of control samples unless indicated otherwise. Surface DR5 is analyzed similarly with an antibody from Imgenex. For sub-G1content and cell cycle profile analysis, all cells are pelleted and ethanol-fixed, followed by staining with propidium iodide in the presence of RNase. Cell viability assays are carried out in 96-well black-walled clear-bottom plates with CellTiter-Glo[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Mice[1]
    For subcutaneous xenografts, 4- to 6-week-old female athymic nu/nu mice are inoculated with 1×106 cells (2.5×106 for T98G) of the indicated cell lines in each rear flank as a 200-μL suspension of 1:1 Matrigel (BD)/PBS. All subcutaneous tumors are allowed to establish for 1 to 4 weeks after injection until reaching a volume of ~125 mm3 before treatment initiation. All intraperitoneal and intravenous injections are given at a total volume of 200 μL. Oral formulations of TIC10 are administered by oral gavage and given as a 200 μL suspension containing 20% Cremophor EL, 10% DMSO, and 70% PBS. Tumors are monitored with digital calipers at indicated time points. All subcutaneous tumors are allowed to establish for 1-4 weeks post-injection until reaching a volume of ~125 mm3 before treatment initiation. Relief of tumor burden is monitored for 3 weeks after disappearance of the tumor and confirmed by visual inspection after euthanasia.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References

    Purity: 99.80%

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    TIC10
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