| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg | |||
| Other Sizes |
| Targets |
UCB-6876 targets tumor necrosis factor-alpha (TNFα), a central pro-inflammatory cytokine involved in the pathogenesis of various inflammatory and autoimmune disorders. TNFα functions as a homotrimer that binds to TNF receptors (TNFR1 and TNFR2) to initiate signaling. UCB-6876 binds to the central cavity of the TNF trimer with a Kd of 22 μM, stabilizing an asymmetric conformation of the trimer that is unable to engage TNF receptors for signaling. This allosteric mechanism of inhibition represents a unique approach to modulating TNFα activity.
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| ln Vitro |
In vitro, UCB-6876 binds to the asymmetric crystalline form of the TNF trimer with a Kd of 22 μM. The compound displays a concentration-dependent response curve and selectivity over the TNFR1 extracellular domain and control proteins. By stabilizing an asymmetric conformation of the TNF trimer that is incompetent for receptor signaling, UCB-6876 effectively inhibits TNFα-mediated signaling pathways in cellular systems.
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| ln Vivo |
In vivo activity data for UCB-6876 are limited. Based on its potent in vitro inhibition of TNFα signaling, the compound is expected to demonstrate anti-inflammatory efficacy in animal models of inflammatory and autoimmune diseases. Typical in vivo studies for TNFα inhibitors involve administration to mouse models of arthritis, inflammatory bowel disease, or other inflammatory conditions, with assessment of disease severity and inflammatory markers.
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| Enzyme Assay |
For non-cellular in vitro binding assays, UCB-6876 is evaluated for its binding affinity to the TNF trimer. The compound is incubated with purified TNFα trimer, and binding is measured using surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), or other biophysical techniques. The binding affinity (Kd of 22 μM) is determined. The compound's ability to stabilize the asymmetric conformation of the TNF trimer is assessed by structural analysis techniques such as X-ray crystallography.
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| Cell Assay |
For in vitro cellular assays, UCB-6876 is tested in TNFα-responsive cell lines to assess its effects on TNFα signaling. Cells are treated with TNFα in the presence or absence of the compound, and downstream signaling is measured by assessing NF-κB activation, cytokine production, or cell survival. The compound's ability to inhibit TNFα-mediated inflammatory responses is quantified. The compound's selectivity over TNFR1 and control proteins is confirmed.
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| Animal Protocol |
For in vivo animal studies, UCB-6876 would typically be evaluated in mouse models of inflammatory and autoimmune diseases. Mice are treated with the compound at various doses via oral or intraperitoneal administration. Disease severity is assessed using clinical scores, histopathological examination, and measurement of inflammatory markers. The compound's ability to modulate TNFα-mediated inflammation is evaluated.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for UCB-6876 are limited. As a small-molecule inhibitor with a molecular weight suitable for oral bioavailability, the compound is expected to have favorable pharmacokinetic properties. Further pharmacokinetic studies would be needed to determine its absorption, distribution, metabolism, and excretion profile. The compound is for research use only and not for human use.
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| Toxicity/Toxicokinetics |
Toxicological data for UCB-6876 are limited. As a TNFα inhibitor that stabilizes an asymmetric conformation of the TNF trimer, the compound may have on-target effects related to TNFα's role in immune function. Comprehensive toxicology studies would be required for therapeutic development. The compound is for research use only and not for human use.
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| References |
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| Additional Infomation |
UCB-6876 is a small-molecule TNFα inhibitor that binds to the central cavity of the TNF trimer, stabilizing an asymmetric conformation that is incompetent for receptor signaling. The compound displays a concentration-dependent response curve and selectivity over the TNFR1 extracellular domain and control proteins. UCB-6876 binds to the TNF trimer with a Kd of 22 μM and is a valuable tool for studying TNF signaling in inflammatory and autoimmune disorders.
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| Molecular Formula |
C17H18N2O
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|---|---|
| Molecular Weight |
266.337624073029
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| Exact Mass |
266.14
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| Elemental Analysis |
C, 76.66; H, 6.81; N, 10.52; O, 6.01
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| CAS # |
637324-45-9
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| PubChem CID |
962431
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
20
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| Complexity |
322
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=C(C=C1)C)CN2C3=CC=CC=C3N=C2CO
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| InChi Key |
RZRPPZWEPMDGEI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H18N2O/c1-12-7-8-13(2)14(9-12)10-19-16-6-4-3-5-15(16)18-17(19)11-20/h3-9,20H,10-11H2,1-2H3
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| Chemical Name |
[1-[(2,5-dimethylphenyl)methyl]benzimidazol-2-yl]methanol
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| Synonyms |
UCB-6876; UCB 6876; UCB6876;
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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 | 3.7546 mL | 18.7730 mL | 37.5460 mL | |
| 5 mM | 0.7509 mL | 3.7546 mL | 7.5092 mL | |
| 10 mM | 0.3755 mL | 1.8773 mL | 3.7546 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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