MST-312 is a potent telomerase inhibitor, with an IC50 value of 0.67μM [1]. MST-312 reduces the activity of telomerase in cells, causing telomere dysfunction, leading to DNA damage and cell growth arrest[2]. MST-312 has been widely used to inhibit the proliferation of leukemia cells, and new combined therapies have been developed to suppress the vitality of tumor cells[3].
In vitro, MST-312 treatment for 72 hours significantly inhibited the viability of PA-1 cells, A2780 cells and OVCAR3 cells, with IC50 values of 4.2μM, 3.9μM and 7.1μM, respectively[4]. Treatment with 8μM MST-312 for 48 hours reduced the cell viability and metabolic activity of U-266 cells and induced cell apoptosis[5]. Treatment with 4μM MST-312 for 48 hours inhibited the proliferation of Jurkat cells and downregulated the expressions of CCND1, MDM2, MYC and HSP90AA1[6]. Treatment with 100μM MST-312 for 18 hours inhibited the replication of HSV-1 virus in HEp-2 cells, reduced the number of cells exhibiting cytopathic effects, and decreased the accumulation of early and late viral proteins[7].
In vivo, MST-312 treatment via oral administration (400mg/kg; 5 times a week) for 6 weeks inhibited the growth of tumor volume in the HBC-4 cell-xenograft mouse model and caused weight loss in mice[8].
References:
[1] Seimiya H, Oh-hara T, Suzuki T, et al. Telomere shortening and growth inhibition of human cancer cells by novel synthetic telomerase inhibitors MST-312, MST-295, and MST-199[J]. Molecular cancer therapeutics, 2002, 1(9): 657-665.
[2] Gurung R L, Lim S N, Low G K M, et al. MST-312 alters telomere dynamics, gene expression profiles and growth in human breast cancer cells[J]. Journal of Nutrigenetics and Nutrigenomics, 2015, 7(4-6): 283-298.
[3] Ghasemimehr N, Farsinejad A, Khalilabadi R M, et al. The telomerase inhibitor MST-312 synergistically enhances the apoptotic effect of doxorubicin in pre-B acute lymphoblastic leukemia cells[J]. Biomedicine & Pharmacotherapy, 2018, 106: 1742-1750.
[4] Fernandes S G, Gala K, Khattar E. Telomerase inhibitor MST-312 and quercetin synergistically inhibit cancer cell proliferation by promoting DNA damage[J]. Translational Oncology, 2023, 27: 101569.
[5] Ameri Z, Ghiasi S, Farsinejad A, et al. Telomerase inhibitor MST-312 induces apoptosis of multiple myeloma cells and down-regulation of anti-apoptotic, proliferative and inflammatory genes[J]. Life Sciences, 2019, 228: 66-71.
[6] Bahmei A, Karimi F, Mahini S M, et al. Targeting telomerase with MST-312 leads to downregulation of CCND1, MDM2, MYC, and HSP90AA1 and induce apoptosis in Jurkat cell line[J]. Medical Oncology, 2024, 41(11): 267.
[7] Haberichter J, Roberts S, Abbasi I, et al. The telomerase inhibitor MST-312 interferes with multiple steps in the herpes simplex virus life cycle[J]. Journal of Virology, 2015, 89(19): 9804-9816.
[8] Fujiwara C, Muramatsu Y, Nishii M, et al. Cell-based chemical fingerprinting identifies telomeres and lamin A as modifiers of DNA damage response in cancer cells[J]. Scientific reports, 2018, 8(1): 14827.
MST-312是一种强效的端粒酶抑制剂，IC50值为0.67µM[1]。MST-312降低细胞中端粒酶的活性，导致端粒功能障碍，从而引起DNA损伤和细胞生长停滞[2]。MST-312已被广泛用于抑制白血病细胞增殖，并用以开发新的联合疗法来抑制肿瘤细胞的活力[3]。
在体外，MST-312处理72小时显著抑制了PA-1细胞、A2780细胞和OVCAR3细胞的活力，IC50值分别为4.2µM、3.9µM和7.1µM[4]。使用8µM的MST-312处理48小时，降低了U-266细胞的活力和代谢活性，并诱导了细胞凋亡[5]。使用4µM的MST-312处理48小时，抑制了Jurkat细胞的增殖，并下调了CCND1、MDM2、MYC和HSP90AA1的表达[6]。使用100µM的MST-312处理18小时，抑制了HSV-1病毒在HEp-2细胞中的复制，减少了表现出细胞病变效应的细胞数量，并降低了早期和晚期病毒蛋白的积累[7]。
在体内，每周5次口服给予MST-312（400mg/kg），持续6周，抑制了HBC-4细胞异种移植小鼠模型中的肿瘤体积生长，并导致小鼠体重下降[8]。