TIC10 (ONC201)

製品コードS7963 バッチS796304

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₄H₂₆N₄O
	分子量	386.49	CAS No.	1616632-77-9
Solubility (25°C)*	体外	DMSO	77 mg/mL warmed with 50ºC water bath (199.22 mM)
		Ethanol	38 mg/mL warmed with 50ºC water bath (98.32 mM)
		Water	Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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]
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]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	SUM159 cells
	濃度	10 uM
	反応時間	24 h
	実験の流れ	Cells were treated with 10 μM ONC201 or DMSO for 24 h.
動物実験	動物モデル	Female athymic nu/nu mice
	投薬量	25, 50, 100 mg/kg
	投与方法	Intraperitoneal/oral

参考

カスタマーフィードバック

: Data from [Data independently produced by , , Oncotarget, 2017, 8(17):28385-28394]

: Data from [Data independently produced by , , Oncotarget, 2017, 8(9):15775-15788]

: Data from [Data independently produced by , , PLOS ONE, 2016, 11(9): e0162133.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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
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
Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2 [ Mol Cell, 2020, 80(6):1104-1122.e9]	PubMed: 33259812
NLGN3 promotes neuroblastoma cell proliferation and growth through activating PI3K/AKT pathway. [ Eur J Pharmacol, 2019, 857:172423]	PubMed: 31150649

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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