OSMI-1 |
Catalog No.GC14870
One-Click Copy Product Info
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OSMI-1 is an O-GlcNAc transferase (OGT) small molecule inhibitor that does not significantly affect other glycosyltransferases.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1681056-61-0
Sample solution is provided at 25 µL, 10mM.
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 cell 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 calvarial 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 by 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.
| 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 | |
| Chemical Name | (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 | ||
| Formula | C28H25N3O6S2 | M.Wt | 563.64 |
| Solubility | 20mg/mL in DMSO, 25mg/mL in DMF | Storage | Store at -20°C,protect from light |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7742 mL | 8.8709 mL | 17.7418 mL |
| 5 mM | 354.8 μL | 1.7742 mL | 3.5484 mL |
| 10 mM | 177.4 μL | 887.1 μL | 1.7742 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)