STC-15 is a potent, selective and orally active inhibitor of RNA methyltransferase METTL3, with an IC50 value of 6.1nM [1]. STC-15 can activate the innate immune pathway and modify the tumor microenvironment (TME), transforming the TME from an immunosuppressive, tumor-promoting state to an immunostimulatory, anti-tumor state[2]. STC-15 has been widely used in inhibiting tumor progression in cell and animal models, as well as in the development of novel combined therapies[3].
In vitro, STC-15 treatment combined with HJP-178 for 7 days significantly inhibited the proliferation of SKOV-3 cells, with IC50 values of 1.194μM[4]. STC-15 treatment (0.5µM) for 48h induced the expression of endogenous IFN signaling in the Caov3 ovarian cell line[5].
In vivo, STC-15 treatment via intraperitoneal injection at a dose of 30mg/kg/day for 2 days significantly reduced the cellular level of m6A in peripheral blood mononuclear cells (PBMC) of SD rats[6].
References:
[1] Tang H, Zhang R, Zhang A. Small-molecule inhibitors targeting RNA m6A modifiers for cancer therapeutics: latest advances and future perspectives[J]. Journal of Medicinal Chemistry, 2025, 68(17): 18114-18142.
[2] Ofir-Rosenfeld Y, Vasiliauskaitė L, Obacz J, et al. Abstract C077: STC-15, a small molecule inhibitor of the RNA methyltransferase METTL3, activates anti-tumor immunity and reshapes the tumor microenvironment[J]. Molecular Cancer Therapeutics, 2023, 22(12_Supplement): C077-C077.
[3] Vasiliauskaite L, Ofir-Rosenfeld Y, Albertella M, et al. Abstract A18: STC-15, a novel METTL3 inhibitor, and its combination with Venetoclax confer anti-tumour activity in AML models[J]. Blood Cancer Discovery, 2023, 4(3_Supplement): A18-A18.
[4] Ou Y J, Liu B J, Xuan Y F, et al. The combination of BET and METTL3 inhibitors elicits synergistic antitumor effects in ovarian cancer cells via reducing SP1 and BCL-2 expression[J]. Life Sciences, 2025, 368: 123505.
[5] Ofir-Rosenfeld Y, Vasiliauskaitė L, Obacz J, et al. STC-15, a small molecule inhibitor of the RNA methyltransferase METTL3, activates anti-tumor immunity and reshapes the tumor microenvironment[C]//MOLECULAR CANCER THERAPEUTICS. 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA: AMER ASSOC CANCER RESEARCH, 2023, 22(12).
[6] Dutheuil G, Oukoloff K, Korac J, et al. Discovery, optimization, and preclinical pharmacology of EP652, a METTL3 inhibitor with efficacy in liquid and solid tumor models[J]. Journal of Medicinal Chemistry, 2025, 68(3): 2981-3003.
STC-15是一种强效、选择性、口服有效的RNA甲基转移酶METTL3抑制剂，IC50值为6.1nM[1]。STC-15可以激活先天免疫通路并改造肿瘤微环境（TME），将TME从免疫抑制、促肿瘤状态转变为免疫刺激、抗肿瘤状态[2]。STC-15已被广泛用于在细胞和动物模型中抑制肿瘤进展，以及用于开发新型联合疗法[3]。
在体外，STC-15联合HJP-178处理7天显著抑制了SKOV-3细胞的增殖，IC50值为1.194μM[4]。STC-15处理（0.5µM）48小时，在Caov3卵巢癌细胞系中诱导了内源性干扰素信号通路的表达[5]。
在体内，通过腹腔注射STC-15，剂量为30mg/kg/day，连续2天，显著降低了SD大鼠外周血单核细胞（PBMC）中的m6A水平[6]。