YM155, a small imidazolium-based compound, potently inhibits survivin promoter activity with an IC50 value of 0.54nM [1]. YM155 can suppress survivin expression through the disruption of SP1 binding to the survivin core promoter and of ILF3–p54/nrb complex[2]. YM155 has been widely used to induce tumor cell apoptosis and promote tumor regression in diverse cell and animal models[3].
In vitro, YM155 treatment for 120 hours significantly inhibited the proliferation of UKF-NB-3 and UKF-NB-6 cells with IC50 values of 0.49 and 0.65nM, respectively[4]. Treatment of H1299 cells with YM155 at 40nM for 24h significantly induced cell death and promoted mitochondrial dysfunction, leading to a reduction in tricarboxylic acid (TCA) cycle intermediates[5]. Treatment with 10nM YM155 for 24 hours significantly inhibited PANC-1 cell viability and induced downregulation of PI3K, p-ERK, and p-STAT3 in PANC-1 cells[6].
In vivo, YM155 treatment via subcutaneous injection at a dose of 2 mg/kg/day for 21 days remarkably reduced tumor growth in the SH-SY5Y cell xenograft model of mice, without affecting body weight[7]. Continuous subcutaneous infusion of YM155 (5mg/kg/day) for 21 days significantly inhibited the development of ascites in Primary effusion lymphoma (PEL) xenograft mice[8].
References:
[1] Nakahara T, Takeuchi M, Kinoyama I, et al. YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts[J]. Cancer research, 2007, 67(17): 8014-8021.
[2] Rauch A, Hennig D, Schäfer C, et al. Survivin and YM155: how faithful is the liaison?[J]. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 2014, 1845(2): 202-220.
[3] Tolcher A W, Quinn D I, Ferrari A, et al. A phase II study of YM155, a novel small-molecule suppressor of survivin, in castration-resistant taxane-pretreated prostate cancer[J]. Annals of oncology, 2012, 23(4): 968-973.
[4] Voges Y, Michaelis M, Rothweiler F, et al. Effects of YM155 on survivin levels and viability in neuroblastoma cells with acquired drug resistance[J]. Cell death & disease, 2016, 7(10): e2410-e2410.
[5] Mondal A, Jia D, Bhatt V, et al. Ym155 localizes to the mitochondria leading to mitochondria dysfunction and activation of AMPK that inhibits BMP signaling in lung cancer cells[J]. Scientific reports, 2022, 12(1): 13135.
[6] Na Y S, Yang S J, Kim S M, et al. YM155 induces EGFR suppression in pancreatic cancer cells[J]. PloS one, 2012, 7(6): e38625.
[7] Li X, Yang F, He N, et al. YM155 inhibits neuroblastoma growth through degradation of MYCN: A new role as a USP7 inhibitor[J]. European Journal of Pharmaceutical Sciences, 2023, 181: 106343.
[8] Kojima Y, Hayakawa F, Morishita T, et al. YM155 induces apoptosis through proteasome-dependent degradation of MCL-1 in primary effusion lymphoma[J]. Pharmacological research, 2017, 120: 242-251.
YM155是一种基于imidazolium的小分子化合物，能有效抑制survivin启动子活性，IC50值为0.54nM[1]。YM155通过破坏SP1与survivin核心启动子的结合，以及干扰ILF3-p54/nrb复合物的形成，从而抑制survivin的表达[2]。YM155已广泛应用于多种细胞和动物模型中，用于诱导肿瘤细胞凋亡并促进肿瘤消退[3]。
在体外，YM155处理120小时可显著抑制UKF-NB-3和UKF-NB-6细胞的增殖，IC50值分别为0.49nM和0.65nM[4]。使用40nM YM155处理H1299细胞24小时，能显著诱导细胞死亡并促进线粒体功能障碍，导致三羧酸(TCA)循环中间产物减少[5]。用10nM的YM155处理PANC-1细胞24小时，可显著抑制细胞活力，并下调PI3K、p-ERK和p-STAT3的表达[6]。
在体内，每日皮下注射2 mg/kg/day剂量的YM155连续21天，能显著抑制SH-SY5Y细胞移植瘤小鼠的肿瘤生长，且不影响体重[7]。持续皮下输注YM155（5 mg/kg/day）21天，可显著抑制原发性渗出性淋巴瘤移植瘤小鼠腹水的形成[8]。