proTAME

proTAME is a cell-permeable APC/C (Anaphase Promoting Complex/Cyclosome) inhibitor^[1]. proTAME is converted to TAME (Tosyl-L-Arginine Methyl Ester) by intracellular esterases, and TAME specifically inhibits the activity of APC/C, thereby inducing cell cycle arrest in metaphase and subsequently leading to cell death^[2]. proTAME is commonly used in research on cell cycle regulation and cancer-related studies^[3][4].

In vitro, proTAME (5, 10, 20, 50 or 100μM; 3h) treatment shows dose-dependent metaphase arrest in mammalian oocytes and early cleavage embryos, and the metaphase arrest induced by this drug does not require spindle assembly checkpoint (SAC) activity^[5]. Treatment of OVCAR-3 cells with proTAME(5, 10, 20, 50 or 100μM; 6h) inhibits cells growth with an IC₅₀ of 12.5μM^[6]. Treatment of MCL and DLBCL cell lines with proTAME (3, 6 and 12µM) for 24h induced a prolonged metaphase, resulting in accumulation of the APC/C-Cdc20 substrate cyclin B1, inactivation/degradation of Bcl-2 and Bcl-xL and caspase-dependent apoptosis^[7].

References:
[1] Zeng, X., Sigoillot, F., Gaur, S., Choi, S., Pfaff, K. L., Oh, D. C., Hathaway, N., Dimova, N., Cuny, G. D., & King, R. W. (2010). Pharmacologic inhibition of the anaphase-promoting complex induces a spindle checkpoint-dependent mitotic arrest in the absence of spindle damage. Cancer cell, 18(4), 382–395.
[2] Zeng, X., & King, R. W. (2012). An APC/C inhibitor stabilizes cyclin B1 by prematurely terminating ubiquitination. Nature chemical biology, 8(4), 383–392.
[3] Lara-Gonzalez, P., & Taylor, S. S. (2012). Cohesion fatigue explains why pharmacological inhibition of the APC/C induces a spindle checkpoint-dependent mitotic arrest. PloS one, 7(11), e49041.
[4] Mayah, A., Arenas, R. B., Bastida, A., & Bolanos-Garcia, V. M. (2025). The Use of APC/C Antagonists to Promote Mitotic Catastrophe in Cancer Cells. Methods in molecular biology (Clifton, N.J.), 2874, 207–213.
[5] Radonova, L., Svobodova, T., Skultety, M., Mrkva, O., Libichova, L., Stein, P., & Anger, M. (2019). ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity. International journal of molecular sciences, 20(18), 4537.
[6] Raab, M., Sanhaji, M., Zhou, S., Rödel, F., El-Balat, A., Becker, S., & Strebhardt, K. (2019). Blocking Mitotic Exit of Ovarian Cancer Cells by Pharmaceutical Inhibition of the Anaphase-Promoting Complex Reduces Chromosomal Instability. Neoplasia (New York, N.Y.), 21(4), 363–375.
[7] Maes, A., Maes, K., De Raeve, H., De Smedt, E., Vlummens, P., Szablewski, V., Devin, J., Faict, S., De Veirman, K., Menu, E., Offner, F., Spaargaren, M., Moreaux, J., Vanderkerken, K., Van Valckenborgh, E., & De Bruyne, E. (2019). The anaphase-promoting complex/cyclosome: a new promising target in diffuse large B-cell lymphoma and mantle cell lymphoma. British journal of cancer, 120(12), 1137–1146.

proTAME是一种细胞渗透性的后期促进复合物/环体（APC/C）抑制剂^[1]。proTAME在细胞内被酯酶转化为TAME（Tosyl-L-Arginine Methyl Ester）,TAME能够特异性地抑制 APC/C 的活性，从而诱导细胞周期停滞在中期，随后导致细胞死亡^[2]。proTAME通常用于细胞周期调控和癌症相关研究^[3][4]。

在体外实验中，proTAME（5、10、20、50 或 100μM；3 小时）处理可不依赖于纺锤体组装检查点（SAC）活性地诱导哺乳动物卵母细胞和早期分裂胚胎发生剂量依赖性的中期停滞^[5]。在卵巢癌细胞系 OVCAR-3 中，proTAME（5、10、20、50 或 100μM； 6 小时）能够抑制细胞生长，其 IC₅₀ 为 12.5μM^[6]。在套细胞淋巴瘤（MCL）和弥漫性大B细胞淋巴瘤（DLBCL）细胞系中，proTAME（3、6 和 12µM）处理 24 小时可诱导细胞中期延长，导致 APC/C-Cdc20 的底物 cyclin B1 积累，Bcl-2 和 Bcl-xL 失活/降解，以及依赖半胱天冬酶的细胞凋亡^[7]。