TIC10 (ONC201)

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.

TIC10 (ONC201) Chemical Structure

TIC10 (ONC201) Chemical Structure

CAS: 1616632-77-9

Selleck's TIC10 (ONC201) has been cited by 16 Publications

3 Customer Reviews

Purity & Quality Control

Batch: Purity: 99.97%
99.97

TIC10 (ONC201) Related Products

Signaling Pathway

Choose Selective Akt Inhibitors

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.
Targets
Akt [1] ERK [1]
In vitro
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]

Cell Research Cell lines SUM159 cells
Concentrations 10 uM
Incubation Time 24 h
Method

Cells were treated with 10 μM ONC201 or DMSO for 24 h.

Experimental Result Images Methods Biomarkers Images 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
In Vivo
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]

Animal Research Animal Models Female athymic nu/nu mice
Dosages 25, 50, 100 mg/kg
Administration Intraperitoneal/oral
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04629209 Withdrawn
Glioblastoma
Masonic Cancer Center University of Minnesota|University of Minnesota
June 28 2024 Phase 2
NCT06012929 Suspended
Meningioma|Refractory Meningioma|Relapsed Meningioma
University of Nebraska|Chimerix
January 2024 Phase 1
NCT05476939 Recruiting
Diffuse Intrinsic Pontine Glioma|Diffuse Midline Glioma H3 K27M-Mutant
Gustave Roussy Cancer Campus Grand Paris|Chimerix|Innovative Therapies For Children with Cancer Consortium
September 29 2022 Phase 3

Chemical Information & Solubility

Molecular Weight 386.49 Formula

C24H26N4O

CAS No. 1616632-77-9 SDF Download TIC10 (ONC201) SDF
Smiles CC1=CC=CC=C1CN2C(=O)C3=C(CCN(C3)CC4=CC=CC=C4)N5C2=NCC5
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 77 mg/mL ( (199.22 mM); Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 77 mg/mL

Water : Insoluble


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In vivo
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