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Technical Data
| Formula | C24H26N4O |
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| Molecular Weight | 386.49 | CAS No. | 1616632-77-9 | |
| Solubility (25°C)* | In vitro | DMSO | 77 mg/mL (199.22 mM) | |
| Ethanol | 38 mg/mL (98.32 mM) | |||
| Water | Insoluble | |||
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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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
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Preparing Stock Solutions
Biological Activity
| Description | TIC10 (ONC201) inactivates Akt and ERK to induce TNF-related apoptosis-inducing ligand (TRAIL) through Foxo3a, possesses superior drug properties: delivery across the blood-brain barrier, superior stability and improved pharmacokinetics. Phase 1/2. | ||
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| 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. [1] |
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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. [1] |
Protocol (from reference)
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References
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Customer Product Validation
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Data from [Data independently produced by , , Oncotarget, 2017, 8(17):28385-28394]
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Data from [Data independently produced by , , Oncotarget, 2017, 8(9):15775-15788]
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Data from [Data independently produced by , , PLOS ONE, 2016, 11(9): e0162133.]
Selleck's TIC10 (ONC201) has been cited by 18 publications
| ONC201/TIC10 enhances durability of mTOR inhibitor everolimus in metastatic ER+ breast cancer [ Elife, 2023, 12e85898] | PubMed: 37772709 |
| ONC201/TIC10 enhances durability of mTOR inhibitor everolimus in metastatic ER+ breast cancer [ Elife, 2023, 12e85898] | PubMed: 37772709 |
| The adaptor protein 14-3-3zeta modulates intestinal immunity and aging in Drosophila [ J Biol Chem, 2023, S0021-9258(23)02442-0] | PubMed: 37918806 |
| Dopamine receptor D2 regulates glioblastoma survival and death through MET and death receptor 4/5 [ Neoplasia, 2023, 39:100894] | PubMed: 36972629 |
| VRK3 depletion induces cell cycle arrest and metabolic reprogramming of pontine diffuse midline glioma - H3K27 altered cells [ Front Oncol, 2023, 13:1229312] | PubMed: 37886173 |
| Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence [ Exp Gerontol, 2023, 173:112091] | PubMed: 36657533 |
| Cooperativity between H3.3K27M and PDGFRA poses multiple therapeutic vulnerabilities in human iPSC-derived diffuse midline glioma avatars [ bioRxiv, 2023, 2023.02.24.528982] | PubMed: 36865329 |
| IMP075 targeting ClpP for colon cancer therapy in vivo and in vitro [ Biochem Pharmacol, 2022, 204:115232] | PubMed: 36030831 |
| ONC201-Induced Mitochondrial Dysfunction, Senescence-like Phenotype, and Sensitization of Cultured BT474 Human Breast Cancer Cells to TRAIL [ Int J Mol Sci, 2022, 23(24)15551] | PubMed: 36555190 |
| Characterization of TR-107, a novel chemical activator of the human mitochondrial protease ClpP [ Pharmacol Res Perspect, 2022, 10(4):e00993] | PubMed: 35929764 |
RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.
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.