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]。