| Description | OSMI-1 is an O-GlcNAc transferase (OGT) inhibitor (IC50=2.7 μM) that is orally active and cell-permeable. OSMI-1 inhibits protein O-GlcNA acetylation without qualitatively altering cell-surface N- or O- linked glycans. |
| In vitro | 方法：COS7 和 Hela 细胞用 OSMI-1 (2-100 µM) 处理 24 h，使用 CCK8 Assay 检测细胞活力。结果：50 µM OSMI-1 使细胞活力降低 50% 以上。[1]方法：CHO 细胞用 OSMI-1 (10-100 µM) 处理 24 h，使用 Western Blot 检测靶点蛋白表达水平。结果：OSMI-1 以剂量依赖的方式减少了全局 OGlcNAcylation，在 50 µM 时达到最大效果。[2] |
| In vivo | 方法：为检测体内抗肿瘤活性，将 OSMI-1 (1 mg/kg，静脉注射) 和 TRAIL (500 µg/kg，腹腔注射) 给药给携带人结直肠癌肿瘤 HCT116 的 BALB/c-Foxn1nu/ArcGem nude 小鼠，每天一次，持续三周。结果：单独用 OSMI-1 或 TRAIL 治疗的小鼠的肿瘤大小略有减小，但在 OSMI-1 和 TRAIL 组合组中显著减小。联合治疗协同提高 HCT116 裸鼠移植瘤的抗肿瘤活性。[3]方法：为研究对 Stx 介导的致病反应的保护作用，将 OSMI-1 (300-1000 µg/mouse in water containing 4.5% DMSO and 5% Tween 80) 腹腔注射给 Stx2a 攻击的 C57BL/6 小鼠，每天一次，持续七天。结果：O-GlcNAc 抑制可以改善小鼠的死亡率和 Stx2a 暴露引起的各种疾病症状，进一步加强了 O-GlcNAc 的抑制作用。[4] |
| Target activity | OGT:2.7 μM |
| molecular weight | 563.64 |
| Molecular formula | C28H25N3O6S2 |
| CAS | 1681056-61-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 18.33 mg/mL (32.53 mM), Sonication is recommended. |
| References | 1. Liu Y, et al. Discovery of a Low Toxicity O-GlcNAc Transferase (OGT) Inhibitor by Structure-based Virtual Screening of Natural Products. Sci Rep. 2017 Sep 26;7(1):12334. 2. Ortiz-Meoz RF, et al. A small molecule that inhibits OGT activity in cells. ACS Chem Biol. 2015 Jun 19;10(6):1392-7. 3. Lee SJ, et al. OSMI-1 Enhances TRAIL-Induced Apoptosis through ER Stress and NF-κB Signaling in Colon Cancer Cells. Int J Mol Sci. 2021 Oct 14;22(20):11073. 4. Lee KS, et al. Inhibition of O-GlcNAcylation protects from Shiga toxin-mediated cell injury and lethality in host. EMBO Mol Med. 2022 Jan 11;14(1):e14678. |
| Citations | 1. Wang N, Yu M, Fu Y, et al. Blocking ATM Attenuates SKOV3 Cell Proliferation and Migration by Disturbing OGT/OGA Expression via hsa-miR-542-5p. Frontiers in Oncology. 2022.12 2. Liu R, Liu Y, Zhang W, et al.PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma.Genes & Diseases.2023: 101114. 3. Wang J, Aniwan A, Liu H, et al.O-GlcNAcylation regulates HIF-1α and induces mesothelial-mesenchymal transition and fibrosis of human peritoneal mesothelial cells.Heliyon.2023 |