ST 045849
目录号 : GC50570
ST 045849是一种O-GlcNAc转移酶(OGT)抑制剂，IC50值为53μM。
Cas No.:442665-87-4
Sample solution is provided at 25 µL, 10mM.
ST 045849 is an inhibitor of O-GlcNAc transferase (OGT), with an IC50 value of 53μM[1]. ST 045849 is currently widely used in the research for screening low toxicity OGT inhibitors[2].
In vitro, ST 045849 treatment significantly inhibited the growth of HKCI-2 cells after 72 hours, with an IC50 value of 50.44nM[3]. Mouse embryonic stem cells were treated with ST 045849 (0.2nM) for 30min exhibited the reduced O-GlcNAcylated Notch1 and Notch1 protein expression in the plasma membrane, accompanied by a reduction in glucose production[4]. ST 045849 treatment (15μM; 6h) can significantly reduce the reactive oxygen species (ROS) levels in NE-4C cells cultured under high glucose concentration (500mg/dl)[5]. ST 045849 treatment (0.4mM) for 2h can significantly inhibit the overall O-GlcNAc glycosylation in adipocytes, and induce an increase in the number of small lipid droplets and the appearance of a small number of extremely large lipid droplets in oleic acid-treated adipocytes[6].
In vivo, ST 045849 treatment (20mg/kg/day) via gavage for 4 days in mouse model of diabetic pregnancy significantly reduced the incidence of neural tube defects in the embryos[5].
References:
[1] Wu X, Wang M, Cao Y, et al. Discovery of a novel OGT inhibitor through high-throughput screening based on homogeneous time-resolved fluorescence (HTRF)[J]. Bioorganic Chemistry, 2023, 139: 106726.
[2] Liu Y, Ren Y, Cao Y, et al. Discovery of a low toxicity O-GlcNAc transferase (OGT) inhibitor by structure-based virtual screening of natural products[J]. Scientific reports, 2017, 7(1): 12334.
[3] Xu W, Zhang X, Wu J, et al. O-GlcNAc transferase promotes fatty liver-associated liver cancer through inducing palmitic acid and activating endoplasmic reticulum stress[J]. Journal of hepatology, 2017, 67(2): 310-320.
[4] Jeon J H, Suh H N, Kim M O, et al. Glucosamine-induced OGT activation mediates glucose production through cleaved Notch1 and FoxO1, which coordinately contributed to the regulation of maintenance of self-renewal in mouse embryonic stem cells[J]. Stem cells and development, 2014, 23(17): 2067-2079.
[5] Kim G, Cao L, Reece E A, et al. Impact of protein O-GlcNAcylation on neural tube malformation in diabetic embryopathy[J]. Scientific Reports, 2017, 7(1): 11107.
[6] Yang Y, Fu M, Li M D, et al. O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity[J]. Nature communications, 2020, 11(1): 181.
ST 045849是一种O-GlcNAc转移酶(OGT)抑制剂，IC50值为53μM[1]。ST 045849目前被广泛用于筛选低毒性OGT抑制剂的研究中[2]。
在体外，ST 045849处理72小时后能显著抑制HKCI-2细胞的生长，IC50值为50.44nM[3]。小鼠胚胎干细胞经0.2nM 浓度的ST 045849处理30分钟后，质膜中O-GlcNAc修饰的Notch1蛋白和Notch1蛋白表达均降低，同时伴随葡萄糖生成减少[4]。在高糖浓度(500mg/dl)培养条件下，15μM浓度的ST 045849处理6小时可显著降低NE-4C细胞中的活性氧水平[5]。0.4mM浓度的ST 045849处理2小时能显著抑制脂肪细胞整体O-GlcNAc糖基化水平，并在油酸处理的脂肪细胞中诱导小脂滴数量增加及少量超大脂滴的出现[6]。
在体内，糖尿病妊娠小鼠模型连续4天灌胃给予20mg/kg/day剂量的ST 045849，能显著降低胚胎神经管缺陷的发生率[5]。
| Cell experiment [1]: | |
Cell lines | ATDC5 cells |
Preparation Method | The chondrocytes (ATDC5 cells) were cultured in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% foetal bovine serum (FBS) and 1% P/S. ATDC5 cells were maintained at 37°C under humidified air with 5% CO2. In order to set up the osteoarthritis cell model, ATDC5 cells were stimulated with 10µg/mL lipopolysaccharide (LPS) for 12h. Meanwhile, ST 045849 was incubated with the cells at a concentration of 10μM for 24 hours. Cell viability of the indicated ATDC5 cells was assessed with the CCK-8 kit. In brief, cells were seeded into 96-well plates at a density of 5000 cells/well and incubated for 48h. After that, each well was added with 10μL CCK-8 cocktail and subjected to further incubation at 37°C for 2h. A microplate reader was used to measure the absorbance value at a wavelength of 450nm. |
Reaction Conditions | 10μM; 24h |
Applications | ST 045849 significantly restored the decreased cell viability of ATDC5 cells induced by LPS. |
| Animal experiment [2]: | |
Animal models | C57BL/6J female mice |
Preparation Method | Ten-week-old female C57BL/6J mice were injected with streptozotocin in 0.1mM citrate buffer at 65mg/kg body weight intravenously. Blood glucose level was measured by tail clipping using Blood Glucose Monitoring System. The value ≥250mg/dl or 14mM indicated diabetes Mellitus (DM). The normal glucose level (~150mg/dl or ~8mM) was restored by subcutaneous implantation of insulin pellets. A group of sham-operated mice was used as non-diabetic (ND) controls. Female mice were mated with normal male mice in the afternoon. The presence of vaginal plug on the following morning was denoted as embryonic (E) day 0.5. Insulin pellets were removed at E5.5 to make the female animals of the DM group hyperglycemic again before the beginning of neurulation at E8.5. Diabetic pregnant mice were given gavage feeding with an OGT inhibitor ST 045849 (20mg/kg/day), suspended in water (vehicle), at E6.5 for 4 days. At E10.5 (late neurulation), mice were sacrificed and the embryos were collected for examination. |
Dosage form | 20mg/kg/day for 4 days; p.o. |
Applications | ST 045849 treatment significantly reduced the incidence of neural tube defects in the embryos of diabetic pregnant mice. |
References: | |
| Cas No. | 442665-87-4 | SDF | |
| Canonical SMILES | OC(C1CC(N(/C(S1)=N/C2=CC=C(C=C2)Cl)CCC34CC5CC(C4)CC(C3)C5)=O)=O | ||
| 分子式 | C23H27ClN2O3S | 分子量 | 446.99 |
| 溶解度 | 44.7mg/mL in DMSO | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2372 mL | 11.1859 mL | 22.3719 mL |
| 5 mM | 0.4474 mL | 2.2372 mL | 4.4744 mL |
| 10 mM | 0.2237 mL | 1.1186 mL | 2.2372 mL |
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动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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- Purity: >98.50%
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