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| 25mg |
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Purity: =99.19%
C25-140 (C-25140; C25140) is a novel, first-in-class and potent inhibitor of RING-E3 ligase (TRAF6) / E2 enzyme (Ubc13) protein-protein interaction (PPI) with potential use for autoimmune and chronic inflammatory diseases. In primary human and murine cells as well as in a number of immune and inflammatory signaling pathways, C25-140 prevents NF-κB from becoming activated. Importantly, in preclinical in vivo mouse models, C25-140 reduced inflammation and enhanced the course of autoimmune psoriasis and rheumatoid arthritis diseases. This highlights the significance of TRAF6 E3 ligase activity in psoriasis and rheumatoid arthritis, and the first-in-class TRAF6-Ubc13 inhibitor C25-140 broadens the toolkit for studying the effect of the ubiquitin system on immune signaling.
| Targets |
TRAF6-Ubc13; NF-κB
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|---|---|
| ln Vitro |
The interaction between TRAF6 and Ubc13 is inhibited by C25-140 in a dose-dependent manner[1].
Effectively inhibiting TRAF6-mediated ubiquitin chain formation is C25-140 (10–30 μM; 2 hours)[1]. C25-140 affects TNFα-induced phosphorylation of IκBα as well as NF-κB-induced target gene expression[1]. In the context of cytokine activation, C25-140 effectively inhibits IL-1β- and TNFα mediated receptor signaling[1]. |
| ln Vivo |
In a mouse model of autoimmune psoriasis caused by R 837, C25-140 (1.5 mg/kg; applied topically to the right ear and the shaved back; twice daily for 6 days) reduces the symptoms of the condition[1].
In the collagen-induced arthritis (CIA) model, C25-140 (6–14 mg/kg; given i.p.; twice daily for 14 days) shows a dose-dependent improvement of RA disease outcome[1]. The Cmax, AUC, t1/2, and Vd are 9.7 g/mL, 274083 ng min/mL, 80.62 min, and 4.13 L/kg, respectively, after treatment with C25-140 (10 mg/kg; i.v.)[1]. Treatment with C25-140 (10 mg/kg; p.o.) reveals that the Cmax, AUC, t1/2, and Vd are, respectively, 3.4 g/mL, 124034 ng min/mL, 127.33 min, and 13.3 L/kg. Treatment with C25-140 (10 mg/kg; i.p.) reveals that the Cmax, AUC, t1/2, and Vd are, respectively, 4.2 g/mL, 100 000 ng min/mL, 184 min, and 25.6 L/kg. |
| Animal Protocol |
R 837-induced psoriasis mouse model (male BALB/c mice)[1]
~1.5 mg/kg Topically to the shaved back and the right ear; twice daily for 6 days |
| References |
| Molecular Formula |
C26H31N7O
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|---|---|
| Molecular Weight |
457.58
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| Exact Mass |
457.259
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| Elemental Analysis |
C, 68.25; H, 6.83; N, 21.43; O, 3.50
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| CAS # |
1358099-18-9
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| Related CAS # |
1358099-18-9
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| Appearance |
Solid powder
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| SMILES |
CC1=C(C(=NN1C2=NN3C(=NN=C3C=C2)C)C)CCC(=O)N4CCC(CC4)CC5=CC=CC=C5
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| InChi Key |
HFKVRXVHZGBRKF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H31N7O/c1-18-23(19(2)32(29-18)25-11-10-24-28-27-20(3)33(24)30-25)9-12-26(34)31-15-13-22(14-16-31)17-21-7-5-4-6-8-21/h4-8,10-11,22H,9,12-17H2,1-3H3
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| Chemical Name |
1-(4-benzylpiperidin-1-yl)-3-[3,5-dimethyl-1-(3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)pyrazol-4-yl]propan-1-one
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| Synonyms |
C25140; C 25140; C-25140; C25-140; C-25-140; C25 140
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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: 41.7~92 mg/mL (91.1~201.1 mM)
Ethanol 92 mg/mL (~201.1 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.55 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.55 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1854 mL | 10.9271 mL | 21.8541 mL | |
| 5 mM | 0.4371 mL | 2.1854 mL | 4.3708 mL | |
| 10 mM | 0.2185 mL | 1.0927 mL | 2.1854 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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