ONC206
目录号 : GC38935
ONC206是一种多巴胺 D2 样受体（DRD2/3/4）拮抗剂，属于依米立酮类药物，IC50为0.21μM-0.32μM。
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.
ONC206是一种多巴胺 D2 样受体（DRD2/3/4）拮抗剂，属于依米立酮类药物，IC50为0.21μM-0.32μM[1]。多巴胺受体属于G蛋白偶联受体家族，在细胞生理功能调节中发挥重要作用，ONC206对其拮抗可干扰肿瘤细胞生长信号的传递[2]。ONC206在多种实体瘤和血液肿瘤治疗研究中展现潜力，包括子宫内膜癌、结直肠癌、急性髓系白血病等[3]。
在体外，ONC206（0-50μM）分别处理ARK1和SPEC-2细胞72小时，通过DRD2/5和TRAIL/DR5 通路显著抑制细胞增殖并呈现出剂量依赖性作用 [4]。使用ONC206（0.2μM）处理U87细胞72h，可抑制GBM细胞增殖与诱导凋亡，降低c-myc蛋白水平，抑制糖酵解和氧化磷酸化，激活SOG代谢通路 [5]。
在体内，ONC206（100mg/kg）通过腹腔注射治疗ARK1-luc细胞异种移植小鼠12天，显著延迟了小鼠肿瘤的生长，并破坏DRD2介导的p38MAPK/ERK/PGC-1α网络导致代谢重编程、糖酵解和氧化磷酸化抑制[6]。ONC206（80mg/kg）通过皮下注射用于治疗通过Huh7 细胞异种移植肿瘤小鼠，能够显著延缓肿瘤生长[7]。
| 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 | ||
| 分子式 | C23H22F2N4O | 分子量 | 408.44 |
| 溶解度 | DMSO: 100 mg/mL (244.83 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4483 mL | 12.2417 mL | 24.4834 mL |
| 5 mM | 0.4897 mL | 2.4483 mL | 4.8967 mL |
| 10 mM | 0.2448 mL | 1.2242 mL | 2.4483 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet