Name: TIC10 (ONC201)
Brand: Selleck Chemicals
SKU: S7963
Rating: 5 (18 reviews)

Spring naar

Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.97%

99.97

Gerelateerde doelwitten	PI3K mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PI4K PP2A
Overig Akt Inhibitoren	SC79 AZD5363 (Capivasertib) MK-2206 Dihydrochloride Ipatasertib (GDC-0068) Perifosine GSK690693 Triciribine (API-2) Afuresertib (GSK2110183) CCT128930 A-674563 HCl

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht	386.49	Formule	C₂₄H₂₆N₄O	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	1616632-77-9	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	Dordaviprone			Smiles	CC1=CC=CC=C1CN2C(=O)C3=C(CCN(C3)CC4=CC=CC=C4)N5C2=NCC5

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 77 mg/mL (199.22 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 77 mg/mL

Water : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	3.850mg/ml (9.96mM)	Taking the 1 mL working solution as an example, add 50 μL of clarified DMSO stock solution of 77 mg/ml to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Targets/IC₅₀/Ki	Akt ERK
In vitro	In a p53-independent manner, TIC10 (ONC201) causes a dose-dependent increase in TRAIL mRNA and induces TRAIL protein localization on the cell surface of several cancer cell lines. It 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. This compound decreases the clonogenic survival of cancer cell lines and spares normal fibroblasts. It 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. The agent 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. It is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor suppressor TRAIL.
In vivo	In the HCT116 p53^−/− xenograft, treatment with TIC10 (ONC201) and TRAIL causes tumor regression to a comparable extent when both are administered as multiple doses. It also induces regression of MDA-MB-231 human triple-negative breast cancer xenografts, whereas TRAIL-treated tumors progressed. In DLD-1 colon cancer xenografts, this compound induces tumor stasis at 1 week after treatment, whereas TRAIL-treated tumors progress after a single dose. A single dose of it also induces a sustained regression of the SW480 xenograft and is equally effective when delivered by intraperitoneal or oral route, suggesting favorable oral bioavailability. It causes tumor-specific cell death by TRAIL-mediated direct and bystander effects and is an effective antitumor agent against orthotopic human glioblastoma multiforme tumors.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/23390247/ [2] https://pubmed.ncbi.nlm.nih.gov/31021596/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	Cleaved PARP / CC3 ATF4 / ATF3 p-GCN2 / GCN2 / p-eIF2a / eIF2a p-p70S6K / p-S6 / p-4EBP1 / 4EBP1 / p-HSF1 / HSF1		29588331
Growth inhibition assay	Cell viability		29588330

Informatie over klinische proeven (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2026-08-13)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT05476939	RECRUITING	Diffuse Intrinsic Pontine Glioma; Diffuse Midline Glioma, H3 K27M-Mutant; Diffuse Midline Glioma, H3K27-altered	Gustave Roussy, Cancer Campus, Grand Paris	2022-09-29	PHASE3
NCT05580562	RECRUITING	H3 K27M; Glioma	Jazz Pharmaceuticals	2023-01-23	PHASE3
NCT05542407	RECRUITING	Endometrial Cancer; Metastasis; Endometrioid Endometrial Cancer; Carcinosarcoma; Serous Adenocarcinoma of Endometrium (Diagnosis); Clear Cell Endometrial Carcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Cell Adenocarcinoma	UNC Lineberger Comprehensive Cancer Center	2023-10-23	PHASE1
NCT05009992	RECRUITING	Diffuse Intrinsic Pontine Glioma; Diffuse Midline Glioma, H3 K27M-Mutant; Recurrent Diffuse Intrinsic Pontine Glioma; Recurrent Diffuse Midline Glioma, H3 K27M-Mutant; Recurrent WHO Grade III Glioma; WHO Grade III Glioma	University of California, San Francisco	2021-10-20	PHASE2
NCT04055649	RECRUITING	Malignant Ovarian Epithelial Tumor; Platinum-Resistant Fallopian Tube Carcinoma; Platinum-Resistant Ovarian Carcinoma; Platinum-Resistant Primary Peritoneal Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Refractory Fallopian Tube Carcinoma; Refractory Ovarian Carcinoma; Refractory Primary Peritoneal Carcinoma	Ira Winer	2020-01-21	PHASE2
NCT05630794	RECRUITING	Colorectal Adenomatous Polyp; Colorectal Carcinoma; Familial Adenomatous Polyposis; Multiple Adenomatous Polyps	National Cancer Institute (NCI)	2025-10-06	PHASE1

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

TIC10 (ONC201) Akt Remmer

Molecuulgewicht: 386.49