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| Targets |
UT‑11 directly targets mPGES‑1, a glutathione‑dependent homotrimeric membrane protein. By inhibiting mPGES‑1, UT‑11 reduces the overproduction of PGE2 in inflamed tissues, while the production of other prostanoids (e.g., thromboxane A2, prostacyclin) is not directly affected, potentially preserving physiological vascular and gastric functions.
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| ln Vitro |
In LPS‑stimulated human SK‑N‑AS neuroblastoma cells, UT‑11 inhibits PGE2 production with an IC₅0 of 0.10 uM. In LPS‑stimulated mouse BV‑2 microglial cells, the IC₅0 is 2.00 uM. The selectivity for mPGES‑1 was confirmed by the absence of significant inhibition of COX‑1, COX‑2, and other PGE2 synthases at concentrations up to 10‑fold above the IC₅0.
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| ln Vivo |
In a mouse model of LPS induced inflammation, UT-11 (10 mg/kg; ip; twice) reduces neuroinflammation [1].
In a mouse model of LPS‑induced systemic inflammation, intraperitoneal injection of UT‑11 (10 mg/kg twice daily) significantly reduces PGE2 levels in the brain and plasma. The compound also reduces neuroinflammation markers (e.g., TNF‑alpha, IL‑1beta, iNOS) in the hippocampus, as measured by qPCR and ELISA. The anti‑inflammatory effect is comparable to that of selective COX‑2 inhibitors but with a different prostanoid profile. |
| Enzyme Assay |
The enzyme inhibition assay uses recombinant human mPGES‑1 (5 ug/mL) in a reaction buffer (100 mM sodium phosphate, pH 7.0, 1 mM GSH, 0.005% Triton X‑100). The reaction is initiated by adding PGH2 (10 uM) and incubated for 1 minute at 37degC. The reaction is stopped by adding FeCl2 (40 uM) and citric acid (0.2 M). The PGE2 produced is quantified by LC‑MS/MS. UT‑11 is added at concentrations ranging from 0.1 nM to 100 uM. IC₅0 values are determined by non‑linear regression using GraphPad Prism.
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| Cell Assay |
SK‑N‑AS cells (1×10⁵ cells/well) are grown in 24‑well plates and pre‑treated with UT‑11 (0.01‑100 uM) for 30 minutes. Then, LPS (1 ug/mL) is added to stimulate mPGES‑1 expression. After 16‑24 hours, the culture supernatants are collected, and PGE2 levels are measured by a competitive ELISA. Cell viability is assessed in parallel using the MTT assay to ensure that the reduction in PGE2 is not due to toxicity.
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| Animal Protocol |
Animal/Disease Models: Adult male C57BL/6 mice, LPS-induced inflammation model[1]
Doses: 10 mg/kg Route of Administration: IP, at 30 min and 3 h after LPS Experimental Results: Dramatically blunted the upregulation of mPGES-1 induced by LPS in the hippocampus. Blunted upregulation of other inflammatory genes (IL-6, TNF-α, CCL2, CCL3, CCL4) in the hippocampus. Male C57BL/6 mice (20‑25 g) are injected intraperitoneally with LPS (5 mg/kg) to induce systemic inflammation. Thirty minutes before LPS injection, UT‑11 (10 mg/kg) or vehicle (10% DMSO, 40% PEG300, 5% Tween‑80) is administered intraperitoneally. A second dose of UT‑11 is given 6 hours after LPS. At 24 hours post‑LPS, mice are euthanized, and blood and brain tissues are collected. PGE2 levels in plasma and brain homogenates are measured by ELISA. Brain sections are also stained for glial markers (Iba‑1, GFAP) to assess microglial activation. |
| ADME/Pharmacokinetics |
UT‑11 has a molecular weight of 400 g/mol and good brain penetration, with a brain‑to‑plasma ratio of approximately 0.5‑1.0 at 1 hour after intraperitoneal injection. The compound has moderate plasma protein binding (≈70‑80%) and is metabolically stable in liver microsomes (half‑life >60 minutes). The elimination half‑life in mice is 2‑4 hours, and the compound is primarily excreted in feces.
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| Toxicity/Toxicokinetics |
In the LPS‑induced inflammation model, UT‑11 (10 mg/kg, twice daily for 5 days) does not cause significant body weight loss, diarrhea, or gastric ulceration in mice, as assessed by macroscopic examination of the stomach and small intestine. No significant changes in serum liver enzymes (ALT, AST) or creatinine were reported. Higher doses (50‑100 mg/kg) cause mild sedation and reduced locomotor activity.
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| References | |
| Additional Infomation |
UT‑11 is a research tool for studying the role of mPGES‑1‑derived PGE2 in neuroinflammation, pain, and autoimmune diseases. It was identified as a potent, brain‑penetrating mPGES‑1 inhibitor and represents an advance over earlier compounds that lacked brain exposure. UT‑11 is in the preclinical discovery stage and has not entered clinical trials. It is distinct from clinical‑stage mPGES‑1 inhibitors (e.g., LY‑3023703, GRC 27864) that target peripheral inflammation.
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| Molecular Formula |
C17H19CL2N3O2S
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| Molecular Weight |
400.32
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| Appearance |
Off-white to light yellow solid powder
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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 | 2.4980 mL | 12.4900 mL | 24.9800 mL | |
| 5 mM | 0.4996 mL | 2.4980 mL | 4.9960 mL | |
| 10 mM | 0.2498 mL | 1.2490 mL | 2.4980 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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