ONC206 |
Katalog-Nr.GC38935
One-Click Copy Product Info
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ONC206 ist ein Analogon des TRAIL-Induktors ONC201.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1638178-87-6
Sample solution is provided at 25 µL, 10mM.
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ONC206 is a dopamine D2-like receptor (DRD2/3/4) antagonist belonging to the imipridone class of drugs, with an IC50 of 0.21μM to 0.32μM [1]. Dopamine receptors belong to the G-protein coupled receptor family and play an important role in regulating cellular physiological functions. Antagonism of these receptors by ONC206 can interfere with the transmission of growth signals in tumor cells[2]. ONC206 has demonstrated potential in therapeutic research for various solid and hematological malignancies, including endometrial cancer, colorectal cancer, acute myeloid leukemia, etc[3].
In vitro, treatment of ARK1 and SPEC-2 cells with ONC206 (0-50μM) for 72 hours significantly inhibited cell proliferation in a dose-dependent manner via the DRD2/5 and TRAIL/DR5 pathways[4]. Treatment of U87 GBM cells with ONC206 (0.2μM) for 72 hours suppressed GBM cell proliferation, induced apoptosis, reduced c-myc protein level, inhibited glycolysis and oxidative phosphorylation, and activated the SOG metabolic pathway[5].
In vivo, intraperitoneal injection of ONC206 (100mg/kg) for 12 days in ARK1-luc cell xenograft mice significantly delayed tumor growth and disrupted the DRD2-mediated p38MAPK/ERK/PGC-1α network, leading to metabolic reprogramming, inhibition of glycolysis and oxidative phosphorylation [6]. Subcutaneous injection of ONC206 (80mg/kg) in Huh7 cells xenograft tumor mice significantly retarded tumor growth[7].
References:
[1] Staley A, Tucker K, Yin Y, et al. Highly potent dopamine receptor D2 antagonist ONC206 demonstrates anti-tumorigenic activity in endometrial cancer. Am J Cancer Res 2021, 11(11):5374-5387.
[2] Wang X, Wang ZB, Luo C, et al. The Prospective Value of Dopamine Receptors on Bio-Behavior of Tumor. J Cancer 2019, 10(7):1622-1632.
[3] Bonner ER, Waszak SM, Grotzer MA, et al. Mechanisms of imipridones in targeting mitochondrial metabolism in cancer cells. Neuro Oncol 2021, 23(4):542-556.
[4] Zhang Y, Huang Y, Yin Y, et al. ONC206, an Imipridone Derivative, Induces Cell Death Through Activation of the Integrated Stress Response in Serous Endometrial Cancer In Vitro. Front Oncol 2020, 10:577141.
[5] Ishida CT, Zhang Y, Bianchetti E, et al. Metabolic Reprogramming by Dual AKT/ERK Inhibition through Imipridones Elicits Unique Vulnerabilities in Glioblastoma. Clin Cancer Res 2018, 24(21):5392-5406.
[6] Paraghamian SE, Qiu J, Hawkins GM, et al. A novel dopamine receptor D2 antagonist (ONC206) potentiates the effects of olaparib in endometrial cancer. Cancer Biol Ther 2023, 24(1):2202104.
[7] Cao J, Cao F, Wang C, et al. ONC206 targeting ClpP induces mitochondrial dysfunction and protective autophagy in hepatocellular carcinoma cells. Neoplasia 2024, 55:101015.
| Cell experiment [1]: | |
Cell lines | ARK1 and SPEC-2 |
Preparation Method | Cells were seeded into 96-well culture plates at a density of 3-5×103cells/well and treated with varying concentrations (0, 0.01, 0.1, 1, 2, 5, 20, 50μM) of ONC206 for 72 hours. MTT (5mg/mL) was added at 5μL/well at the end of treatment. After 1h of incubation, the MTT reaction was terminated through the addition of DMSO at 100μL/well. Absorbance was measured at 575nm using a microplate reader. |
Reaction Conditions | 0, 0.01, 0.1, 1, 2, 5, 20 and 50μM; 1h |
Applications | ONC206 inhibits the viability of endometrial cancer cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female athymic mice |
Preparation Method | At 6 weeks of age, ARK1 cells with a density of 4×106luciferase labeling were intraperitoneally injected into female thymus mice to establish tumors. After 2 weeks, the animals were randomized into three groups for treatment with PBS, ONC201, or ONC206; 100mg/kg ONC201 or ONC206 was administered intraperitoneally twice per week for 6 weeks. The tumor volumes were measured and quantified using the IVIS-Lumina XR in vivo imaging system. |
Dosage form | 100mg/kg; twice per week for 6 weeks |
Applications | ONC206 significantly reduces the uterine tumor burden in the mouse model of xenotransplantation. |
References: | |
| Cas No. | 1638178-87-6 | SDF | |
| Canonical SMILES | O=C1N(CC2=CC=C(F)C=C2F)C3=NCCN3C4=C1CN(CC5=CC=CC=C5)CC4 | ||
| Formula | C23H22F2N4O | M.Wt | 408.44 |
| Löslichkeit | DMSO: 100 mg/mL (244.83 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4483 mL | 12.2417 mL | 24.4834 mL |
| 5 mM | 489.7 μL | 2.4483 mL | 4.8967 mL |
| 10 mM | 244.8 μL | 1.2242 mL | 2.4483 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 25 reference(s) in Google Scholar.)