| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
TNF (Kd = 13 nM); NF-κB (Kd = 202 nM)
UCB-9260 targets tumor necrosis factor (TNF), a key pro-inflammatory cytokine involved in various inflammatory and autoimmune diseases. It acts by binding to trimeric TNF with a Kd of 13 nM and stabilizing an asymmetric form of the trimer, thereby inhibiting TNF signaling. By blocking TNF signaling, it inhibits the activation of NF-κB, a transcription factor that drives the expression of inflammatory genes. |
|---|---|
| ln Vitro |
UCB-9260 (0-10 μM) inhibits NF-κB with a geometric mean IC50 of
202 nM after TNF (10 pM) stimulation in in Hek-293 cells[1].
UCB-9260 inhibits TNF-dependent cytotoxicity with a geometric mean
IC50 of 116 nM and a geometric mean IC50 of 120 nM, using human and
mouse TNF, respectively.
|
| ln Vivo |
UCB-9260 (150 mg/kg; p.o.;twice daily for 7 days) shows a
significant reduction of the clinical score. UCB-9260 (10-300 mg/kg;
p.o.) dose-dependently inhibits human and mouse TNF-induced neutrophil
recruitment to the peritoneal compartment in adult male Balb/c mice[1].
Animal Model: Aged 6-8 weeks adult male Balb/c mice ( CAIA model Dosage: 150 mg/kg Administration: p.o.; twice daily for 7days Result:
Showed a significant reduction of the clinical score.
In vivo, UCB-9260 is an orally active TNF inhibitor. As an orally bioavailable compound, it can be administered to animal models of inflammatory diseases. Its ability to inhibit TNF signaling and NF-κB activation translates to in vivo anti-inflammatory efficacy. The compound has been studied in preclinical models of inflammatory and autoimmune diseases. Detailed in vivo pharmacokinetic and efficacy studies are available. |
| Enzyme Assay |
In vitro receptor binding assays for UCB-9260 involve measuring its binding affinity to TNF. The compound is incubated with trimeric TNF at various concentrations, and binding is measured using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The Kd of 13 nM is determined from binding curves. NF-κB activation assays are performed using reporter gene systems in cells stimulated with TNF.
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| Cell Assay |
For in vitro cell-based assays, cells expressing TNF receptors are cultured and treated with UCB-9260 at various concentrations. TNF signaling inhibition is confirmed by measuring NF-κB activation using reporter gene assays or by measuring the expression of NF-κB target genes via qRT-PCR. Cell viability is assessed by MTT or standard assays. The compound's selectivity for TNF over other superfamily members is confirmed using related cytokines.
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| Animal Protocol |
In vivo animal studies with UCB-9260 are conducted in models of inflammatory diseases. The compound is administered orally at doses determined from pharmacokinetic studies. Efficacy is measured by assessing inflammatory markers, tissue damage, or disease severity. Pharmacodynamic markers such as NF-κB activation and cytokine levels are measured in tissues. The compound's oral bioavailability and in vivo efficacy have been demonstrated.
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| ADME/Pharmacokinetics |
UCB-9260 (CAS: 1515888-53-5) has a molecular weight of 423.51 g/mol and a molecular formula of C26H25N5O. Appearance: solid powder. Solubility: DMSO. Storage: -20°C. The compound is an orally active TNF inhibitor that binds to TNF with a Kd of 13 nM and inhibits TNF-stimulated NF-κB activation with an IC50 of 202 nM.
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| Toxicity/Toxicokinetics |
UCB-9260 is a research compound and is not approved for human therapeutic use. In preclinical studies, it has shown a manageable safety profile. As a TNF inhibitor, it may have effects on normal immune function. However, its mechanism of stabilizing an asymmetric TNF trimer is distinct from traditional TNF antagonists. Standard laboratory safety precautions should be followed when handling the compound.
|
| References | |
| Additional Infomation |
UCB-9260 is an orally active small molecule that inhibits tumor necrosis factor (TNF) signaling by stabilizing an asymmetric form of the TNF trimer. It binds to TNF with a Kd of 13 nM and inhibits TNF-stimulated NF-κB activation with an IC50 of 202 nM. It has a molecular weight of 423.51 g/mol and a molecular formula of C26H25N5O. It is not FDA-approved and is intended for research use only.
|
| Molecular Formula |
C26H25N5O
|
|---|---|
| Molecular Weight |
423.509605169296
|
| Exact Mass |
423.21
|
| Elemental Analysis |
C, 73.74; H, 5.95; N, 16.54; O, 3.78
|
| CAS # |
1515888-53-5
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| Related CAS # |
1515888-53-5
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| PubChem CID |
72700327
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| Appearance |
Brown to gray solid
|
| LogP |
3.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
|
| Complexity |
613
|
| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=C(C=C1)C)CN2C3=C(C=CC(=C3)C4=CN(N=C4)C)N=C2C(C5=CC=NC=C5)O
|
| InChi Key |
RZGFWGNCSYUEPR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H25N5O/c1-17-4-5-18(2)21(12-17)16-31-24-13-20(22-14-28-30(3)15-22)6-7-23(24)29-26(31)25(32)19-8-10-27-11-9-19/h4-15,25,32H,16H2,1-3H3
|
| Chemical Name |
[1-[(2,5-dimethylphenyl)methyl]-6-(1-methylpyrazol-4-yl)benzimidazol-2-yl]-pyridin-4-ylmethanol
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| Synonyms |
UCB-9260; UCB9260; UCB 9260
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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) |
DMSO: 85~125 mg/mL (200.7~295.2 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (14.76 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3612 mL | 11.8061 mL | 23.6122 mL | |
| 5 mM | 0.4722 mL | 2.3612 mL | 4.7224 mL | |
| 10 mM | 0.2361 mL | 1.1806 mL | 2.3612 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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