| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
|
Purity: ≥98%
TIC10 (ONC-201, NSC-350625), an imipridone compound, is a novel, potent, orally bioavailable, brain/BBB penetrant, and stable tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) inducer with potential anticancer activity. It was initially developed in the 1970s as an anti-seizure agent which acts by inhibiting Akt and ERK, consequently activating Foxo3a and significantly inducing cell surface TRAIL. TIC10 can inactivate Akt and ERK to induce TRAIL through Foxo3a, possesses superior drug properties: delivery across the blood-brain barrier, superior stability and improved pharmacokinetics. TIC10 is a potent, orally active, and stable small molecule that transcriptionally induces TRAIL in a p53-independent manner. TIC10 induces a sustained up-regulation of TRAIL in tumors and normal cells that may contribute to the demonstrable antitumor activity of TIC10.
| Targets |
Akt; ERK
|
|---|---|
| ln Vitro |
In several cancer cell lines, TIC10 induces TRAIL protein localization on the cell surface in a p53-independent manner and increases TRAIL mRNA in a dose-dependent manner. While TIC10 exhibits broad-spectrum anti-tumor activity in vitro and causes TRAIL-sensitive HCT116 p53/p53 cells to exhibit an increase in sub-G1 DNA content indicative of cell death, normal fibroblasts are unaffected by TIC10 at equivalent doses. TIC10 spares healthy fibroblasts while reducing the clonogenic survival of cancer cell lines. Similar to TRAIL-mediated apoptosis, TIC10 increases the proportion of sub-G1 DNA in cancer cells in a p53-independent and Bax-dependent manner. The up-regulation of TRAIL caused by TIC10 is dependent on Foxo3a, which also up-regulates the TRAIL death receptor DR5 and other targets, possibly making some TRAIL-resistant tumor cells susceptible. ERK and Akt kinases are inactivated by TIC10, which causes Foxo3a to move into the nucleus and bind to the TRAIL promoter to activate gene transcription. Foxo3a is then transported into the nucleus. The effective antitumor drug TIC10 works by increasing the levels of the naturally occurring tumor suppressor TRAIL in tumor cells and their surrounding tissue. [1]
|
| ln 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 one week after treatment, whereas TRAIL-treated tumors advance after a single dose. The SW480 xenograft also exhibits a sustained regression after receiving a single dose of TIC10, and this effect is seen whether the drug is administered orally or intraperitoneally. This suggests that TIC10 has a favorable oral bioavailability. 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]
|
| Cell Assay |
Cells were treated with 10 μM ONC201 or DMSO for 24 h.
|
| Animal Protocol |
Female athymic nu/nu mice
25, 50, 100 mg/kg Intraperitoneal/oral |
| References |
| Molecular Formula |
C24H26N4O
|
|
|---|---|---|
| Molecular Weight |
386.49
|
|
| Exact Mass |
386.21066
|
|
| Elemental Analysis |
C, 74.58; H, 6.78; N, 14.50; O, 4.14
|
|
| CAS # |
1616632-77-9
|
|
| Related CAS # |
41276-02-2 (isomer);1616632-77-9;1638178-82-1 (HCl);1777785-71-3 (HBr);2007141-57-1 (2HBr);
|
|
| Appearance |
White to off-white solid powder
|
|
| SMILES |
O=C1C(CN(CC2=CC=CC=C2)CC3)=C3N(CC4=CC=CC=C4C)C5=NCCN15
|
|
| InChi Key |
RSAQARAFWMUYLL-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C24H26N4O/c1-18-7-5-6-10-20(18)16-28-22-11-13-26(15-19-8-3-2-4-9-19)17-21(22)23(29)27-14-12-25-24(27)28/h2-10H,11-17H2,1H3
|
|
| Chemical Name |
7-benzyl-4-(2-methylbenzyl)-1,2,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(4H)-one
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|---|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5874 mL | 12.9369 mL | 25.8739 mL | |
| 5 mM | 0.5175 mL | 2.5874 mL | 5.1748 mL | |
| 10 mM | 0.2587 mL | 1.2937 mL | 2.5874 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT06012929 | Not yet recruiting | Drug: ONC201 | Meningioma Refractory Meningioma |
University of Nebraska | January 2024 | Phase 1 |
| NCT04629209 | Not yet recruiting | Drug: ONC201 | Glioblastoma | Masonic Cancer Center, University of Minnesota |
June 28, 2024 | Phase 2 |
| NCT05630794 | Not yet recruiting | Procedure: Biopsy Drug: Dordaviprone |
Colorectal Carcinoma Colorectal Adenomatous Polyp |
National Cancer Institute (NCI) |
May 13, 2023 | Phase 1 |
| NCT03932643 | Recruiting | Drug: ONC201 | Acute Myeloid Leukemia Myelodysplastic Syndromes |
University of Nebraska | July 30, 2019 | Phase 1 |
| NCT04055649 | Recruiting | Drug: Paclitaxel Drug: Akt/ERK Inhibitor ONC201 |
Malignant Ovarian Epithelial Tumor | Ira Winer | January 21, 2020 | Phase 2 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA