AT 56 is an orally active and selective inhibitor of lipocalin-type prostaglandin D synthase (L-PGDS), with an IC50 value of 95µM[1]. AT 56 can inhibit leptin production and PGD2 production and affect cell proliferation[2]. AT 56 has been widely used to regulate the endothelial-to-mesenchymal transition (EndMT) process in cancer cell models[3].
In vitro, AT 56 treatment (100µM) for 48h inhibited cell proliferation and c-myc expression in diffuse large B-cell lymphoma (DLBCL) cells[4]. Treatment with 5µM AT 56 for 7 days significantly inhibited the development of wild-type oligodendrocytes without affecting cell survival[5]. Treatment with 5µM AT 56 for 10min inhibited PGD2 production in TE671 cells cultured under serum starvation conditions[6].
In vivo, AT 56 treatment via oral administration at a dose of 30mg/kg/day for 4 weeks reduced the ethanol-induced increase in vascular branching in the cerebral cortex of C57BL/6J mice and decreased L-PGDS expression[7]. Intraperitoneal injection of AT 56 (10mg/kg/day) for 7 days partially rescued the reproductive dysfunction of Clpxfl/fl; Zp3-Cre mice by inhibiting PGD2 synthesis[8].
References:
[1] Irikura D, Aritake K, Nagata N, et al. Biochemical, functional, and pharmacological characterization of AT-56, an orally active and selective inhibitor of lipocalin-type prostaglandin D synthase[J]. Journal of Biological Chemistry, 2009, 284(12): 7623-7630.
[2] Urade Y. Biochemical and structural characteristics, gene regulation, physiological, pathological and clinical features of lipocalin-type prostaglandin D2 synthase as a multifunctional lipocalin[J]. Frontiers in Physiology, 2021, 12: 718002.
[3] Omori K, Morikawa T, Kunita A, et al. Lipocalin-type prostaglandin D synthase‐derived PGD2 attenuates malignant properties of tumor endothelial cells[J]. The Journal of pathology, 2018, 244(1): 84-96.
[4] Hu S, Ren S, Cai Y, et al. Glycoprotein PTGDS promotes tumorigenesis of diffuse large B-cell lymphoma by MYH9-mediated regulation of Wnt–β-catenin–STAT3 signaling[J]. Cell Death & Differentiation, 2022, 29(3): 642-656.
[5] Pan L, Trimarco A, Zhang A J, et al. Oligodendrocyte-lineage cell exocytosis and L-type prostaglandin D synthase promote oligodendrocyte development and myelination[J]. Elife, 2023, 12: e77441.
[6] Fujimori K, Aritake K, Urade Y. Enhancement of prostaglandin D2 production through cyclooxygenase-2 and lipocalin-type prostaglandin D synthase by upstream stimulatory factor 1 in human brain-derived TE671 cells under serum starvation[J]. Gene, 2008, 426(1-2): 72-80.
[7] Li J, Li C, Subedi U, et al. The Role of Endothelial L-PGDS in the Pro-Angiogenic and Anti-Inflammatory Effects of Low-Dose Alcohol Consumption[J]. Cells, 2024, 13(23): 2007.
[8] Hua R, Hai Z, Gu J, et al. AT-56 RESCUES OOCYTE DYSFUNCTION IN OOCYTE-SPECIFIC KNOCKOUT CLPX MICE BY INHIBITING PGD2 SYNTHESIS[J]. Fertility and Sterility, 2024, 122(4): e171.
AT 56是一种口服有效的脂钙蛋白型前列腺素D合成酶（L-PGDS）选择性抑制剂，IC50值为95µM[1]。AT 56能够抑制瘦素产生和PGD2合成，并影响细胞增殖[2]。AT 56已广泛应用于癌细胞模型中调控内皮-间质转化过程[3]。
在体外，使用100µM的AT 56处理弥漫大B细胞淋巴瘤(DLBCL)细胞48小时，可抑制细胞增殖并降低c-myc表达[4]。用5µM的AT 56处理野生型少突胶质细胞7天，能显著抑制其发育过程而不影响细胞存活[5]。在血清饥饿条件下培养的TE671细胞中，5µM的AT 56处理10分钟即可抑制PGD2的生成[6]。
在体内，通过每日口服30mg/kg/day剂量的AT 56连续4周，可减轻乙醇诱导的C57BL/6J小鼠大脑皮层血管分支增生，并降低L-PGDS表达[7]。每日腹腔注射10mg/kg/day剂量的AT 56（连续7天），能通过抑制PGD2合成，部分挽救Clpxfl/fl; Zp3-Cre小鼠的生殖功能障碍[8]。