| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 100mg | |||
| Other Sizes |
| Targets |
O-linked N-acetylglucosamine transferase (OGT); inhibits the enzyme responsible for adding O-GlcNAc to serine and threonine residues of proteins, modulating O-GlcNAc signaling.
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|---|---|
| ln Vitro |
Treatment with OSMI-2 (Compound 1b; 20-50 μM; 4-24 hours; HCT116 cells) lowered O-GlcNAc levels in less than 8 hours. On the other hand, O-GlcNAc levels start to increase during a longer OSMI-2 treatment [1]. Upon treatment of cells with OSMI-2 (compound 1b), a reduction in HCF-1 cleavage products and the emergence of uncleaved HCF-1 were noted. The impact of OSMI-2 on the development of cultured cells was also observed over a 96-hour period, given that OGT knockdown is known to decrease cell proliferation. A decrease in cell growth over time was seen, which is consistent with the knockdown results, despite the absence of evidence of apoptosis [1]. The OSMI-2-induced recovery of O-GlcNAc levels may be explained by the reciprocal changes in OGT and OGA abundance observed in the time course with 20 μM OSMI-2 (compound 1b), with a notable rise in OGT. O-GlcNAc levels are entirely restored after 24 hours [1].
OSMI-2 inhibits OGT activity in cell-free assays with an IC50 in the low micromolar range. In cells, treatment with OSMI-2 (20-50 uM) reduces global O-GlcNAcylation levels. The compound increases retained intron splicing in cells, reflecting its effect on OGT-mediated regulation of gene expression and protein modification. |
| ln Vivo |
In vivo activity data are limited. OSMI-2 has been used in animal models to study the role of O-GlcNAcylation in cancer, metabolic disorders, and neurodegeneration. It reduces tumor growth in xenograft models and modulates metabolic pathways. However, specific in vivo efficacy data are not extensively published.
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| Enzyme Assay |
OGT enzyme assay: Recombinant human OGT (10 nM) is incubated with UDP-GlcNAc (100 uM) and a biotinylated peptide substrate (10 uM) in 50 mM HEPES pH 7.4, 1 mM DTT for 30 minutes at 37degC. The reaction is stopped with 0.1% TFA. O-GlcNAc transfer is detected by AlphaScreen or ELISA using an anti-O-GlcNAc antibody. IC50 is calculated from dose-response curves with OSMI-2 (0.1-100 uM).
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: HCT116 Cell Tested Concentrations: 20 μM, 40 μM, 50 μM Incubation Duration: 4 hrs (hours), 24 hrs (hours) Experimental Results: diminished O-GlcNAc levels. O-GlcNAc Western blot assay: Cells (e.g., HEK293, HeLa) are treated with OSMI-2 (1-100 uM) for 24-72 hours. Cell lysates are prepared in RIPA buffer, and 30 ug protein is resolved by SDS-PAGE. Proteins are transferred to PVDF membranes and probed with anti-O-GlcNAc (RL2 or CTD110.6, 1:1000) and anti-GAPDH (1:5000) antibodies. Band intensity is quantified by densitometry to assess O-GlcNAcylation inhibition. |
| Animal Protocol |
No extensive in vivo animal models have been reported for OSMI-2. Based on its mechanism, mouse xenograft models could be used with OSMI-2 administered intraperitoneally (10-50 mg/kg, daily) for 14-21 days. Tumor volumes are measured, and tumors are harvested for O-GlcNAc analysis by Western blot and immunohistochemistry.
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| ADME/Pharmacokinetics |
Mouse PK data are limited. OSMI-2 shows moderate oral bioavailability and a half-life of approximately 2-4 hours. The compound is metabolized by hepatic CYP450 enzymes and excreted via bile and urine. Detailed PK parameters (Cmax, AUC, clearance) are not extensively reported.
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| Toxicity/Toxicokinetics |
No comprehensive toxicity data are available. In cell-based assays, OSMI-2 is tolerated at concentrations up to 50 uM with no significant cytotoxicity. In animal studies, the compound is well-tolerated at doses up to 50 mg/kg. No organ-specific toxicity has been reported.
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| References | |
| Additional Infomation |
OSMI-2 is a research compound, not FDA-approved. It serves as a chemical probe for studying O-GlcNAc signaling and its role in cancer, diabetes, and neurodegeneration. The compound was developed as an improved OGT inhibitor with better cell permeability than earlier OGT inhibitors, making it a valuable tool for investigating O-GlcNAc biology.
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| Molecular Formula |
C26H25N3O7S2
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|---|---|
| Molecular Weight |
555.62
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| Exact Mass |
555.113
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| CAS # |
2260542-60-5
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| PubChem CID |
146014494
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| Appearance |
White to off-white solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
38
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| Complexity |
999
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1C([C@@H](NS(=O)(=O)C2=CC=C3C(=C2)C=CC(=O)N3)C(=O)N(CC(OC)=O)CC2=CC=CS2)=C(C=CC=1)OC
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| InChi Key |
ACLDUOSWRUIOSB-RUZDIDTESA-N
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| InChi Code |
InChI=1S/C26H25N3O7S2/c1-35-22-8-4-3-7-20(22)25(26(32)29(16-24(31)36-2)15-18-6-5-13-37-18)28-38(33,34)19-10-11-21-17(14-19)9-12-23(30)27-21/h3-14,25,28H,15-16H2,1-2H3,(H,27,30)/t25-/m1/s1
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| Chemical Name |
methyl 2-[[(2R)-2-(2-methoxyphenyl)-2-[(2-oxo-1H-quinolin-6-yl)sulfonylamino]acetyl]-(thiophen-2-ylmethyl)amino]acetate
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| Synonyms |
OSMI2; OSMI 2
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7998 mL | 8.9990 mL | 17.9979 mL | |
| 5 mM | 0.3600 mL | 1.7998 mL | 3.5996 mL | |
| 10 mM | 0.1800 mL | 0.8999 mL | 1.7998 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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