SRI-37330 hydrochloride is a small molecule inhibitor of thioredoxin interacting protein (TXNIP) [1]. SRI-37330 hydrochloride helps protect β cells and increase their number by reducing TXNIP levels, thereby improving insulin secretion capacity [2-3]. SRI-37330 hydrochloride is mainly used to treat diabetes [4].
In adult murine ventricular cardiomyocytes (AMVCs), SRI-37330 hydrochloride (0-5μM; 24h) dose-dependently inhibited the expression of cleaved-Casp1 and TXNIP/NLRP3 in Doxorubicin-treated AMVCs [5]. In FTOoe A549 cells, SRI-37330 hydrochloride (10μM; 24h) significantly reduced the expression of TXNIP protein in cells and abolished the increase in the expression of pyroptosis-related proteins [6]. In rat INS-1 cells, SRI-37330 hydrochloride can significantly inhibit the expression of TXNIP [7].
In diabetic mice model, basal glucose production in the liver of mice treated with SRI-37330 hydrochloride (100mg/kg; po; 3 weeks) was significantly downregulated [7]. In high fat diet mice model, oral SRI-37330 hydrochloride (100mg/kg; po; 4 weeks) treatment protects against high-fat diet-induced glucose intolerance [8].
References:
[1]. Choi EH, Park SJ. TXNIP: A key protein in the cellular stress response pathway and a potential therapeutic target. Experimental & molecular medicine. 2023 Jul; 55(7): 1348-1356.
[2]. Datta S, Rahman MA, Koka S, et al. Mitigation of nicotine-induced podocyte injury through inhibition of thioredoxin interacting protein. Biomedicine & Pharmacotherapy. 2025 Jun 1; 187: 118110.
[3]. Dalle S, Abderrahmani A, Renard E. Pharmacological inhibitors of β-cell dysfunction and death as therapeutics for diabetes. Frontiers in endocrinology. 2023 Mar 15; 14: 1076343.
[4]. Demir S, Nawroth PP, Herzig S, et al. Emerging targets in type 2 diabetes and diabetic complications. Advanced Science. 2021 Sep; 8(18): 2100275.
[5]. Ma Y, Wang Y, Chen R, et al. Exosomal transfer of pro-pyroptotic miR-216a-5p exacerbates anthracycline cardiotoxicity through breast cancer-heart pathological crosstalk. Signal Transduction and Targeted Therapy. 2025 May 14;10(1):1-26.
[6]. Xie WM, Su W, Liu XY, et al. FTO deficiency alleviates LPS-induced acute lung injury by TXNIP/NLRP3-mediated alveolar epithelial cell pyroptosis. American Journal of Respiratory Cell and Molecular Biology. 2024 May; 70(5): 351-363.
[7]. Thielen LA, Chen J, Jing G, et al. Identification of an anti-diabetic, orally available small molecule that regulates TXNIP expression and glucagon action. Cell Metabolism. 2020 Sep 1; 32(3): 353-365.
[8]. Jo S, Jing G, Chen J, et al. Oral TIX100 protects against obesity‐associated glucose intolerance and diet‐induced adiposity. Diabetes, Obesity and Metabolism. 2025 Apr; 27(4): 2223-2231.
SRI-37330 hydrochloride是硫氧还蛋白相互作用蛋白（TXNIP）的小分子抑制剂 [1]。SRI-37330 hydrochloride通过降低TXNIP水平来保护β细胞并增加其数量，从而提高胰岛素分泌能力 [2-3]。SRI-37330 hydrochloride主要用于治疗糖尿病 [4]。
在成年小鼠心室肌细胞（AMVC）中，SRI-37330 hydrochloride（0-5μM；24h）剂量依赖性地抑制了经Doxorubicin处理的AMVC中cleaved-Casp1和TXNIP/NLRP3的表达 [5]。在 FTOoe A549细胞中，SRI-37330 hydrochloride（10μM；24h）显著降低了细胞中TXNIP蛋白的表达，并消除了细胞焦亡相关蛋白表达的增加 [6]。在大鼠INS-1细胞中，SRI-37330 hydrochloride可显著抑制TXNIP的表达 [7]。
在糖尿病小鼠模型中，经SRI-37330 hydrochloride（100mg/kg；po；3周）治疗的小鼠肝脏基础葡萄糖生成显著下调 [7]。在高脂饮食小鼠模型中，口服SRI-37330 hydrochloride（100mg/kg；po；4周）治疗可预防高脂饮食引起的葡萄糖不耐受 [8]。