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TIC10

SKU: orb1300153
FeaturedFeatured Product

Description

TIC-10 (ONC-201) is a clinical-stage small molecule that induces TRAIL expression via Foxo3a activation following Akt/ERK inhibition. Its favorable drug-like properties, including blood-brain barrier penetration, support its investigation in both in vitro and in vivo cancer research models, particularly for oncology and neuro-oncology applications.

Research Area

Cell Biology

Images & Validation

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TIC10

Key Properties

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CAS Number1616632-77-9
MW386.49
Purity>98%
FormulaC24H26N4O
SMILESCc1ccccc1CN1C2=NCCN2C2=C(CN(Cc3ccccc3)CC2)C1=O
TargetProtease
SolubilitySoluble in DMSO (up to 25 mg/ml with warming)

Bioactivity

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In Vivo
TIC10 and TRAIL treatment causes tumor regression in the HCT116 p53 / xenograft to a comparable extent when both are administered as multiple doses. TIC10 also induces regression of MDA-MB-231 human triple-negative breast cancer xenografts, whereas TRAIL-treated tumors progressed. In DLD-1 colon cancer xenografts, TIC10 induces tumor stasis at 1 week after treatment, whereas TRAIL-treated tumors progresses 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. TIC10 causes tumor-specific cell death by TRAIL-mediated direct and bystander effects. TIC10 is an effective antitumor agent against orthotopic human glioblastoma multiforme tumors.
In Vitro
TIC10 causes a dose-dependent increase in TRAIL mRNA and induces TRAIL protein localization on the cell surface of several cancer cell lines in a p53-independent manner. TIC10 has broad-spectrum activity against multiple malignancies in vitro and induces an increase in sub-G1 DNA content suggestive of cell death in TRAIL-sensitive HCT116 p53 / cells, but does not alter the cell cycle profiles of normal fibroblasts at equivalent doses. TIC10 decreases the clonogenic survival of cancer cell lines and spares normal fibroblasts. TIC10 increases the percentage of sub-G1 DNA in cancer cells in a p53-independent and Bax-dependent manner, as previously reported for TRAIL-mediated apoptosis. TIC10-induced TRAIL up-regulation is Foxo3a-dependent, which also up-regulates TRAIL death receptor DR5 among other targets, potentially allowing for sensitization of some TRAIL-resistant tumor cells. 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. TIC10 is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor suppressor TRAIL.
Cell Research
TIC10 is prepared in DMSO and stored, and then diluted with appropriate medium before use. 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.

Storage & Handling

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Storage-20°C
Expiration Date12 months from date of receipt.
DisclaimerFor research use only

Alternative Names

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ONC201; Dordaviprone

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  • TIC10 Isomer

    TIC10 Isomer [orb1300538]

    99.25% (May vary between batches)

    41276-02-2

    386.49

    C24H26N4O

    1 ml x 10 mM (in DMSO), 5 mg, 10 mg, 25 mg, 50 mg
  • TIC10

    TIC10 [orb1222637]

    >98% (HPLC)

    1616632-77-9

    386.49

    C24H26N4O

    5 mg, 10 mg, 25 mg, 50 mg, 100 mg, 200 mg, 500 mg, 1 g
Quality Guarantee

Quality Guarantee

Explore bioreagents carefree to elevate your research. All our products are rigorously tested for performance. If a product does not perform as described on its datasheet, our scientific support team will provide expert troubleshooting, a prompt replacement, or a refund. For full details, please see our Terms & Conditions and Buying Guide. Contact us at [email protected].

Compound Identifiers

PubChem CID
73777259 ↗

Key Properties

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No computed properties available.

Protocol Information

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5 mg
$ 180.00
25 mg
$ 350.00
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