Torin 1 is a potent ATP-competitive mammalian target of rapamycin (mTOR) inhibitor with an IC50 value of 3nM[1]. Torin 1 inhibits both mTORC1/2 complexes with IC50 values between 2 and 10nM[2]. Torin 1 is a potent autophagy inducer[3].
In vitro, treatment of glioblastoma (GB) LN-18 cells with Torin 1 (300, 1000nM) for 24h dose-dependently inhibited cell proliferation and migration and significantly inhibited cell entry into the S phase[4]. Treatment of S. pombe cells with Torin 1 (25μM) for 24h inhibited cell growth but did not cause cell death or G1 phase arrest[5].
In vivo, oral treatment of mice with dextran sulfate sodium (DSS)-induced colitis with Torin 1 (10, 20mg/kg) for 6 days significantly reduced pathological damage in the colon tissue and inhibited the production of proinflammatory cytokines in mice[6]. Torin 1 (400nM, 0.5μL) injected bilaterally into the insular cortex (IC) of nerve-injured rats significantly alleviated neuropathic pain and inhibited the increase in phosphorylated p70S6K (p-p70S6K) levels[7].
References:
[1] Thoreen C C, Kang S A, Chang J W, et al. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1[J]. Journal of Biological Chemistry, 2009, 284(12): 8023-8032.
[2] Sun S Y. mTOR kinase inhibitors as potential cancer therapeutic drugs[J]. Cancer letters, 2013, 340(1): 1-8.
[3] Xu S, Li L, Li M, et al. Impact on autophagy and ultraviolet B induced responses of treatment with the MTOR inhibitors rapamycin, everolimus, torin 1, and pp242 in human keratinocytes[J]. Oxidative medicine and cellular longevity, 2017, 2017(1): 5930639.
[4] Amin A G, Jeong S W, Gillick J L, et al. Targeting the mTOR pathway using novel ATP-competitive inhibitors, Torin1, Torin2 and XL388, in the treatment of glioblastoma[J]. International journal of oncology, 2021, 59(4): 83.
[5] Atkin J, Halova L, Ferguson J, et al. Torin1-mediated TOR kinase inhibition reduces Wee1 levels and advances mitotic commitment in fission yeast and HeLa cells[J]. Journal of cell science, 2014, 127(6): 1346-1356.
[6] Liu T, Zheng S, Guo P. Effect of Torin 1 on suppressing inflammation in mice with dextran sodium sulfate-induced colitis[J]. Int J Clin Exp Med, 2017, 10(3): 4723-4731.
[7] Choi S, Kim K, Cha M, et al. mTOR signaling intervention by Torin1 and XL388 in the insular cortex alleviates neuropathic pain[J]. Neuroscience Letters, 2020, 718: 134742.
Torin 1是一种有效的ATP竞争性哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂，IC50值为3nM[1]。Torin 1抑制两种mTORC1/2复合物，IC50值在2和10nM之间[2]。Torin 1是一种有效的自噬诱导剂[3]。
在体外，Torin 1（300, 1000nM）处理胶质母细胞瘤（GB） LN-18细胞24h，剂量依赖性地抑制了细胞增殖和迁移，并显著抑制了细胞进入S期[4]。Torin 1（25μM）处理S. pombe细胞24h，抑制了细胞的生长，但不会造成细胞死亡或G1期阻滞[5]。
在体内，Torin 1（10, 20mg/kg）通过口服治疗葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠6天，显著减轻了小鼠结肠组织的病理损伤，抑制了促炎细胞因子的产生[6]。Torin 1（400nM, 0.5μL）通过双侧注射到神经损伤大鼠的岛叶皮层（IC），显著减轻了神经性疼痛，抑制了磷酸化p70S6K（p-p70S6K）水平的升高[7]。