SW033291 is a small molecule inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme that catalyzes the oxidation and inactivation of PGE2 [1]. SW033291 was to promote tissue regeneration and prevent kidney and liver injury by upregulating PGE2 levels [2-3]. SW033291 is commonly used to promote tissue regeneration and repair [4].
In Muscle-derived stem cells (MDSCs), SW033291 (20, 50, 100, 500, 1000nM; 24h) increased the production of PGE2 by MDSCs both in GM and DM, and MDSCs were well-tolerated to SW033291 in various concentrations with strong proliferation potential [5]. In marrow mesenchymal stem cells (BMSCs), GelMA ICC combined with SW033291 (1μM; 5d) were able to regulate the M2 macrophage polarization in the co-culture with BMSCs system [6].
In mouse model of liver ischemia-reperfusion, SW033291 (5mg/kg; ip; 72h) increases PGE2 levels in liver tissue and improves liver injury after hepatic ischemia-reperfusion [3]. In T2DM mouse model, SW033291 (5mg/kg; ip; 10 weeks) improves abnormal glucose and lipid metabolism [7]. In T2DM mouse model, SW033291 (5mg/kg; ip; 10 weeks) improved impaired glucose tolerance and insulin resistance [8].
References:
[1]. Cheng H, Huang H, Guo Z, et al. Role of prostaglandin E2 in tissue repair and regeneration. Theranostics. 2021 Aug 13; 11(18): 8836.
[2]. Miao S, Lv C, Liu Y, et al. Pharmacologic blockade of 15-PGDH protects against acute renal injury induced by LPS in mice. Frontiers in physiology. 2020 Mar 13; 11: 138.
[3]. Xie M, He R, Wang H, et al. Effects of small molecule inhibitor SW033291 on hepatic ischemia-reperfusion injury in mice. Biochemical and biophysical research communications. 2022 Jul 30; 615: 70-74.
[4]. Zhang Y, Desai A, Yang SY, et al. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science. 2015 Jun 12; 348(6240): aaa2340.
[5]. Dong Y, Li Y, Zhang C, et al. Effects of SW033291 on the myogenesis of muscle-derived stem cells and muscle regeneration. Stem cell research & therapy. 2020 Dec; 11: 1-7.
[6]. Jiang Q, Bai G, Liu X, et al. 3D GelMA ICC scaffolds combined with SW033291 for bone regeneration by modulating macrophage polarization. Pharmaceutics. 2021 Nov 16; 13(11): 1934.
[7]. Liang M, Wang L, Wang W. The 15-hydroxyprostaglandin dehydrogenase inhibitor SW033291 ameliorates abnormal hepatic glucose metabolism through PGE2–EP4 receptor–AKT signaling in a type 2 diabetes mellitus mouse model. Cellular Signalling. 2023 Aug 1; 108: 110707.
[8]. Wang W, Liang M, Wang L, et al. 15-Hydroxyprostaglandin dehydrogenase inhibitor SW033291 ameliorates hepatic abnormal lipid metabolism, ER stress, and inflammation through PGE2/EP4 in T2DM mice. Bioorganic chemistry. 2023 Aug 1; 137: 106646.
SW033291是15-羟基前列腺素脱氢酶（15-PGDH）的小分子抑制剂，15-PGDH是一种催化PGE2氧化和失活的酶 [1]。SW033291通过上调PGE2水平来促进组织再生并预防肾脏和肝脏损伤 [2-3]。SW033291常用于促进组织再生和修复 [4]。
在肌肉来源的干细胞（MDSC）中，SW033291（20、50、100、500、1000nM；24h）可增加肌肉来源的干细胞的GM和DM中的PGE2生成，MDSC对不同浓度的SW033291均具有良好的耐受性，并具有强大的增殖潜力 [5]。在骨髓间充质干细胞（BMSCs）中，GelMA ICC与SW033291（1μM；5d）联合应用，能够在与BMSCs共培养的体系中调节M2巨噬细胞极化 [6]。
在小鼠肝脏缺血再灌注模型中，SW033291（5mg/kg；ip；72h）可提高肝组织中PGE2水平，改善肝脏缺血再灌注后的肝损伤 [3]。在2型糖尿病小鼠模型中，SW033291（5mg/kg；ip；10周）可改善异常的糖脂代谢 [7]。在2型糖尿病小鼠模型中，SW033291（5mg/kg；ip；10周）可改善糖耐量受损和胰岛素抵抗 [8]。