ONC212
目录号 : GC34095
ONC212是ONC201的化学类似物，是一种氟化咪唑啉酮。
Cas No.:1807861-48-8
Sample solution is provided at 25 µL, 10mM.
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ONC212, a chemical analogue of ONC201, is a fluorinated imipridone[1]. ONC212 is a selective agonist of the orphan GPCR (G protein-coupled receptor) GPR132/G2A, with an EC50 of approximately 400nM[2]. ONC212 is commonly used in the study of pancreatic cancer[1], colorectal cancer[3], and acute myeloid leukemi[4].
ONC212 (5-20μM, 20-60μM; 48h) significantly reduced the number of viable cells in HeLa (IC50 = 16µM) and A549 (IC50 = 54µM) cells in a dose-dependent manner. ONC212 (5µM, 50µM; 48h) markedly increased early and late apoptosis in HeLa and A549 cells compared to their respective untreated controls[5].
ONC212 (50mg/kg/day; 23 days, 29 days; i.g.) exhibited significantly greater tumor growth inhibition than ONC201 in Capan-2 and PANC-1 xenograft models. ONC212 (50mg/kg, 3 times every week; 25 days, 54 days; i.g.) exhibited significantly greater tumor growth inhibition than the control group in the HPAF-II and BxPC-3 xenograft models[6].
References:
[1] Tajiknia V, Pinho-Schwermann M, Srinivasan P R, et al. Synergistic anti-tumor activity, reduced pERK, and immuno-stimulatory cytokine profiles with 5-FU or ONC212 plus KRAS G12D inhibitor MRTX1133 in CRC and pancreatic cancer cells independent of G12D mutation[J]. American Journal of Cancer Research, 2024, 14(9): 4523.
[2] Prabhu V V, Madhukar N, Tarapore R, et al. Potent anti-cancer effects of selective GPR132/G2A agonist imipridone ONC212 in leukemia and lymphoma[J]. Cancer Research, 2017, 77(13_Supplement): 1155-1155.
[3] Ferrarini I, Louie A, Zhou L, et al. ONC212 is a novel mitocan acting synergistically with glycolysis inhibition in pancreatic cancer[J]. Molecular cancer therapeutics, 2021, 20(9): 1572-1583.
[4] Nii T, Prabhu V V, Ruvolo V, et al. Imipridone ONC212 activates orphan G protein-coupled receptor GPR132 and integrated stress response in acute myeloid leukemia[J]. Leukemia, 2019, 33(12): 2805-2816.
[5] Basu V, Shabnam, Murghai Y, et al. ONC212, alone or in synergistic conjunction with Navitoclax (ABT-263), promotes cancer cell apoptosis via unconventional mitochondrial-independent caspase-3 activation[J]. Cell Communication and Signaling, 2024, 22(1): 441.
[6] Lev A, Lulla A R, Wagner J, et al. Anti-pancreatic cancer activity of ONC212 involves the unfolded protein response (UPR) and is reduced by IGF1-R and GRP78/BIP[J]. Oncotarget, 2017, 8(47): 81776.
ONC212是ONC201的化学类似物，是一种氟化咪唑啉酮[1]。ONC212是孤儿G蛋白偶联受体（GPCR）GPR132/G2A的选择性激动剂，EC50约为400nM[2]。ONC212常用于胰腺癌[1]、结直肠癌[3]和急性髓系白血病[4]的研究。
ONC212（5-20μM，20-60μM；48h）以剂量依赖的方式显著降低了HeLa（IC50 = 16μM）和A549（IC50 = 54μM）细胞中的活细胞数量。与各自的未处理对照组相比，ONC212（5μM，50μM；48h）显著增加了HeLa和A549细胞的早期和晚期凋亡[5]。
在Capan-2和PANC-1异种移植瘤模型中，ONC212（50mg/kg/天；23天，29天；灌胃）的肿瘤生长抑制作用显著强于ONC201。在HPAF-II和BxPC-3异种移植瘤模型中，ONC212（50mg/kg，每周3次；25天，54天；灌胃）的肿瘤生长抑制作用显著强于对照组[6]。
| Cell experiment [1]: | |
Cell lines | Human cervical cell line HeLa and lung alveolar cancer cell line A549 |
Preparation Method | HeLa and A549 cells were seeded in 96 well plates. Subsequently, they were treated with ONC212 at different concentration ranges (5-20μM for HeLa cells and 20-60μM for A549 cells) for 48h. After treatment, MTT solution was added and incubated for 3h at 37°C. The solvent was added to dissolve the formazan crystal and after 30min, absorbance was measured at 590nm. |
Reaction Conditions | 5-20μM, 20-60μM; 48h |
Applications | ONC212 significantly reduced the number of viable cells in HeLa (IC50 = 16µM) and A549 (IC50 = 54µM) cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Human pancreatic cancer cell lines mouse model |
Preparation Method | Six- to seven-week-old female athymic nu/nu mice were acclimated for 1 week on arrival to the animal facility before in-vivo study was initiated. A total of 3-5×106 luciferase-expressing cells were suspended in 50μl of PBS mixed with 50μl of Matrigel and subcutaneously injected into the rear flanks of the mice. When tumor volume reached an average of 100-150cm3, mice were randomly assigned to the indicated control or treatment groups. ONC201 and ONC212 were delivered in a solution of 10% DMSO, 20% Kolliphor® EL, and 70% PBS by oral gavage at a dose of 50mg/kg, administered either daily (for PANC-1 and Capan-2 models) or three times a week (for HPAF-II and BxPC3 models). The length (L) and width (W) of the tumors were measured 1-2 times a week using a digital caliper, and the volume of the tumor was calculated using the formula: 0.5*L*W^2. Mice were also weighed once a week to monitor signs of drug toxicity. |
Dosage form | 50mg/kg, 3 or 7 times every week; 23 days, 25 days, 29 days, 54 days; i.g. |
Applications | ONC212 exhibited significantly greater tumor growth inhibition than ONC201 in Capan-2 and PANC-1 xenograft models. ONC212 exhibited significantly greater tumor growth inhibition than the control group in the HPAF-II and BxPC-3 xenograft models. |
References: | |
| Cas No. | 1807861-48-8 | SDF | |
| Canonical SMILES | O=C1N(CC2=CC=C(C(F)(F)F)C=C2)C3=NCCN3C4=C1CN(CC5=CC=CC=C5)CC4 | ||
| 分子式 | C24H23F3N4O | 分子量 | 440.46 |
| 溶解度 | DMSO : 50 mg/mL (113.52 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 | 2.2704 mL | 11.3518 mL | 22.7035 mL |
| 5 mM | 454.1 μL | 2.2704 mL | 4.5407 mL |
| 10 mM | 227 μL | 1.1352 mL | 2.2704 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
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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