OSMI-1
目录号 : GC14870
OSMI-1是一种O-GlcNAc转移酶（OGT）小分子抑制剂，不会显著影响其他糖基转移酶。
Cas No.:1681056-61-0
Sample solution is provided at 25 µL, 10mM.
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OSMI-1 is an O-GlcNAc transferase (OGT) small molecule inhibitor that does not significantly affect other glycosyltransferases [1]. OSMI-1 inhibited full length human OGT (ncOGT) with an IC50 value of 2.7 µM [2].
OSMI-1 ranging from 10 to 100 µM treated inhibited global O-GlcNAcylation in Chinese hamster ovary (CHO) cells with the maximal effect being achieved at 50 µM [2]. 50 µM OSMI-1 treated CHO cells decreased viability by about 50% after 24 h [2]. OSMI-1 (40 µM) decreased total-O-GlcNAc by 30% in both TamS and TamR cells lines [1]. TamR cells were significantly more sensitive to OSMI-1 than the parental TamS cells, with OSMI-1-EC50 value of ~15 µM in TamR and ~ 40 µM in TamS by activity for proliferation assay [1]. OSMI-1 (40 µM, 24 h) increased expression of OGT and DDIT3 in both TamS and TamR cells while ERα is downregulated [1]. The levels of intracellular and secreted HBsAg, but not HBeAg, in the supernatants increased in primary human hepatocytes (PHHs) and HepG2.2.15 cells after OSMI-1 treatment [3].
OSMI-1 reduced osteoclast differentiation in vivo by disrupting the translocation of NF-κB p65 and nuclear factor of activated T cells c1 (NFATc1) into the nucleus by controlling their PTM O-GlcNAcylation. OSMI-1 treatment effectively inhibited lipopolysaccharide (LPS)-induced formation of TRAP-positive osteoclasts in the cavarial surface compared to the mice injected with the vehicle, while OSMI-1 significantly reduced the number of TRAP-specific mature osteoclasts in the calvarial surfaces and sections [4]. The tumor size in mice treated with TRAIL or OSMI-1 alone was slightly reduced compared with the control group but was significantly reduced (5-fold) in the TRAIL and OSMI-1 combination group on HCT116 Xenograft in Nude Mice. Compared with vehicle-treated xenograft mice, the levels of ER stress-related proteins, such as IRE1α, PERK, p-JNK, CHOP and DR5, were increased when either TRAIL or OSMI-1 was administered alone, whereas these effects were even greater for the combination treatment [5].
References:
[1]. Barkovskaya A, Seip K, Prasmickaite L, et al. Inhibition of O-GlcNAc transferase activates tumor-suppressor gene expression in tamoxifen-resistant breast cancer cells[J]. Scientific reports, 2020, 10(1): 1-10.
[2]. Ortiz-Meoz R F, Jiang J, Lazarus M B, et al. A small molecule that inhibits OGT activity in cells[J]. ACS chemical biology, 2015, 10(6): 1392-1397.
[3]. Wang X, Lin Y, Liu S, et al. O-GlcNAcylation modulates HBV replication through regulating cellular autophagy at multiple levels[J]. The FASEB Journal, 2020, 34(11): 14473-14489.
[4].Kim M J, Kim H S, Lee S, et al. Hexosamine Biosynthetic Pathway-Derived O-GlcNAcylation Is Critical for RANKL-Mediated Osteoclast Differentiation[J]. International Journal of Molecular Sciences, 2021, 22(16): 8888.
[5]. Lee S J, Lee D E, Choi S Y, et al. OSMI-1 enhances TRAIL-induced apoptosis through ER stress and NF-κB signaling in colon cancer cells[J]. International journal of molecular sciences, 2021, 22(20): 11073.
OSMI-1是一种O-GlcNAc转移酶（OGT）小分子抑制剂，不会显著影响其他糖基转移酶[1]。OSMI-1抑制全长人OGT（ncOGT），IC50值为2.7µM[2]。
10至100µM的OSMI-1处理抑制了中国仓鼠卵巢（CHO）细胞的整体O-GlcNAcylation，在50µM时达到最大效果[2]。50µM OSMI-1处理的CHO细胞在24小时后活力降低约50%[2]。OSMI-1（40µM）使TamS和TamR细胞系中的总-O-GlcNAc降低了30%[1]。TamR细胞对OSMI-1的敏感性明显高于亲代TamS细胞，通过增殖活性测定，TamR中OSMI-1-EC50值约为15µM，TamS中OSMI-1-EC50值为约40µM[1]。OSMI-1（40µM，24小时）增加了TamS和TamR细胞中OGT和DDIT3的表达，而ERα下调[1]。OSMI-1处理后，原代人肝细胞（PHHs）和HepG2.2.15细胞上清液中细胞内和分泌的HBsAg水平增加，但HBeAg水平没有增加[3]。
OSMI-1通过控制其PTM-O-GlcNAcylation，破坏NF-κB p65和活化T细胞核因子c1（NFATc1）向细胞核的易位，从而在体内减少破骨细胞分化。与注射载体的小鼠相比，OSMI-1治疗有效抑制了脂多糖（LPS）诱导的颅骨表面TRAP阳性破骨细胞的形成，而OSMI-1显著减少了颅骨表面和切片中TRAP特异性成熟破骨细胞数量[4]。与对照组相比，单独用TRAIL或OSMI-1处理的小鼠中的肿瘤大小略有减小，但在裸小鼠中的HCT116异种移植物上，TRAIL和OSMI-1组合组中的肿瘤尺寸显著减小（5倍）。与载体处理的异种移植物小鼠相比，当单独施用TRAIL或OSMI-1时，ER应激相关蛋白（如IRE1α、PERK、p-JNK、CHOP和DR5）的水平增加，而联合治疗的这些作用甚至更大[5]。
| Cell experiment [1]: | |
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Cell lines |
Tamoxifen-sensitive (TamS) and tamoxifen-resistant (TamR) MCF7 breast cancer cells |
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Preparation Method |
TamS and TamR cells were collected on ice following 24 h of treatment with 40 µM dose of OSMI-1 compound, or DMSO. Samples were immediately fixed in 100% ice-cold methanol and placed in - 20 °C for storage. Samples were washed in cold PBS and stained with 1.5 µg/ml Hoechst 33258 in PBS for 30 min at 37 °C. Cell cycle analysis was then performed on LSR II flow cytometer. |
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Reaction Conditions |
40 µM for 24 h |
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Applications |
OSMI-1 decreased the number of cells in S-Phase and also caused a modest, but not significant, accumulation of cells in the G2-M phase |
| Animal experiment [2]: | |
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Animal models |
HCT116 xenograft models on Five-week-old female BALB/c-Foxn1nu/ArcGem nude mice |
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Preparation Method |
HCT116 xenograft models were injected subcutaneously with 5 × 106 cells in the flanks of each mouse. After 7 days, tumor-bearing mice (tumor volume approximately 90-110 mm3) were randomized into various treatment groups (n = 4/group) as follows: Group 1—mice were administered DMSO as a vehicle control; Group 2—mice were administered TRAIL (500 µg/kg/daily, Intraperitoneal); Group 3—mice were administered OSMI-1(1 mg/kg/daily, Intravenous); Group 4—mice were coadministered TRAIL and OSMI-1 for 21 consecutive days. |
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Dosage form |
1 mg/kg/daily, i.v. |
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Applications |
The tumor size in mice treated with TRAIL or OSMI-1 alone was slightly reduced compared with the control group but was significantly reduced (5-fold) in the TRAIL and OSMI-1 combination group. |
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References: [1]: Barkovskaya A, Seip K, Prasmickaite L, et al. Inhibition of O-GlcNAc transferase activates tumor-suppressor gene expression in tamoxifen-resistant breast cancer cells[J]. Scientific reports, 2020, 10(1): 1-10. |
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| Cas No. | 1681056-61-0 | SDF | |
| 化学名 | (R)-N-(furan-2-ylmethyl)-2-(2-methoxyphenyl)-2-(2-oxo-1,2-dihydroquinoline-6-sulfonamido)-N-(thiophen-2-ylmethyl)acetamide | ||
| Canonical SMILES | O=C(N(CC1=CC=CS1)CC2=CC=CO2)[C@H](NS(C3=CC(C=C4)=C(C=C3)NC4=O)(=O)=O)C5=CC=CC=C5OC | ||
| 分子式 | C28H25N3O6S2 | 分子量 | 563.64 |
| 溶解度 | 20mg/mL in DMSO, 25mg/mL in DMF | 储存条件 | Store at -20°C,protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7742 mL | 8.8709 mL | 17.7418 mL |
| 5 mM | 0.3548 mL | 1.7742 mL | 3.5484 mL |
| 10 mM | 0.1774 mL | 0.8871 mL | 1.7742 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
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Quality Control & SDS
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- Purity: >98.00%
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