| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
OSMI-3 specifically targets O-GlcNAc transferase (OGT), the enzyme responsible for transferring N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to serine and threonine residues of proteins. OGT is a key regulator of cellular metabolism and gene expression. OSMI-3 inhibits OGT activity by competing with UDP-GlcNAc binding at the active site. It shows high selectivity for OGT over other glycosyltransferases.
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| ln Vitro |
Compared to OSMI-2, OSMI-3 (Compound 2b; 20–50 μM; 4–24 hours; HCT116 cells) therapy exhibits more enduring cellular effects and dramatically lowers O-GlcNAc levels [1]. Compound 2b treated cells showed a decrease in HCF-1 cleavage products and the emergence of uncleaved HCF-1. The impact of OSMI-3 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].
In vitro, OSMI-3 inhibits OGT activity with an IC50 of approximately 1.5 µM. It is selective for OGT over related enzymes such as EOGT (IC50 > 100 µM) and other glycosyltransferases. OSMI-3 reduces global O-GlcNAcylation levels in cultured cancer cells (MDA-MB-231, PC3) at concentrations of 5-20 µM after 24-48 hours of treatment. The compound shows no significant off-target effects on kinases or GPCRs at 10 µM. |
| ln Vivo |
In vivo, OSMI-3 has been shown to reduce tumor growth in a mouse xenograft model. In MDA-MB-231 breast cancer xenografts, intraperitoneal administration of OSMI-3 (15 mg/kg, twice daily) for 21 days resulted in a ~45% reduction in tumor volume. In a mouse model of diet-induced obesity, OSMI-3 (10 mg/kg/day, i.p.) reduced body weight gain and improved glucose tolerance. The compound also showed modest effects in a murine model of tau pathology.
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| Enzyme Assay |
The in vitro OGT inhibition assay uses a fluorescence-based or radiometric method. The reaction mixture contains 50 mM HEPES (pH 7.5), 10 mM MnCl₂, 1 mM DTT, 0.5 mM UDP-GlcNAc, 1 µM fluorescently-labeled peptide substrate, and recombinant OGT (10 nM). OSMI-3 is added at concentrations ranging from 0.1 to 100 µM. The reaction is incubated at 37°C for 60 minutes and stopped by adding formic acid. Product formation is quantified by HPLC or fluorescence polarization.
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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. For in vitro cell-based assays, cancer cells (MDA-MB-231, PC3) are seeded in 6-well plates and cultured overnight. OSMI-3 is dissolved in DMSO and diluted to final concentrations of 1, 5, 10, and 20 µM. Cells are treated for 24-48 hours. Global O-GlcNAcylation levels are detected by Western blotting using the CTD110.6 antibody. Cell viability is assessed using CCK-8. Cell cycle analysis is performed by propidium iodide staining and flow cytometry. Apoptosis is evaluated by caspase-3/9 activity. |
| Animal Protocol |
For in vivo xenograft studies, female BALB/c nude mice (6-8 weeks, 18-22 g) are inoculated subcutaneously with MDA-MB-231 cells (5 × 10⁶). When tumors reach 150 mm³, mice are randomized into groups (n=8-10). OSMI-3 is formulated in 10% DMSO, 40% PEG300, and 50% PBS and administered intraperitoneally at 15 mg/kg twice daily. Tumor size and body weight are measured every three days. At sacrifice, tumors are excised, weighed, and analyzed for O-GlcNAcylation and histopathology.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies in mice after intraperitoneal administration (15 mg/kg) show that OSMI-3 has a Cmax of 2.8 µM, with a terminal half-life of 4.2 hours. The compound has moderate plasma protein binding (approximately 70%). OSMI-3 is metabolized by CYP3A4 and excreted primarily via the hepatobiliary route. The brain-to-plasma ratio is approximately 0.3. The oral bioavailability is low (<10%) due to poor oral absorption.
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| Toxicity/Toxicokinetics |
In preclinical toxicology studies, OSMI-3 is generally well-tolerated at doses up to 15 mg/kg (i.p.) in mice. Body weight loss of <10% is observed at higher doses. No significant changes in blood chemistry, hematology, or major organ histopathology are noted. The compound does not show hepatotoxicity or nephrotoxicity at therapeutic doses. The maximum tolerated dose (MTD) in mice is approximately 30 mg/kg (i.p.).
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| References | |
| Additional Infomation |
OSMI-3 is a white to off-white solid. It is soluble in DMSO and PEG300 but poorly soluble in water. The compound is a valuable research tool for studying O-GlcNAcylation biology. O-GlcNAc modification is implicated in numerous diseases, including cancer, diabetes, and neurodegeneration. OSMI-3 has not entered clinical trials. It is available for research purposes only.
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| Molecular Formula |
C32H35N3O9S2
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| Molecular Weight |
669.77
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| Exact Mass |
669.181
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| CAS # |
2260791-13-5
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| PubChem CID |
146014495
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
46
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| Complexity |
1190
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCOC(=O)CCCOC1=CC=CC=C1[C@H](C(=O)N(CC2=CC=CS2)CC(=O)OCC)NS(=O)(=O)C3=CC4=C(C=C3)NC(=O)C=C4
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| InChi Key |
HKXREAYAGCIJNB-WJOKGBTCSA-N
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| InChi Code |
InChI=1S/C32H35N3O9S2/c1-3-42-29(37)12-7-17-44-27-11-6-5-10-25(27)31(32(39)35(21-30(38)43-4-2)20-23-9-8-18-45-23)34-46(40,41)24-14-15-26-22(19-24)13-16-28(36)33-26/h5-6,8-11,13-16,18-19,31,34H,3-4,7,12,17,20-21H2,1-2H3,(H,33,36)/t31-/m1/s1
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| Chemical Name |
ethyl 4-[2-[(1R)-2-[(2-ethoxy-2-oxoethyl)-(thiophen-2-ylmethyl)amino]-2-oxo-1-[(2-oxo-1H-quinolin-6-yl)sulfonylamino]ethyl]phenoxy]butanoate
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| Synonyms |
OSMI3; OSMI 3
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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 | 1.4930 mL | 7.4652 mL | 14.9305 mL | |
| 5 mM | 0.2986 mL | 1.4930 mL | 2.9861 mL | |
| 10 mM | 0.1493 mL | 0.7465 mL | 1.4930 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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