C25-140 |
Catalog No.GC34513
One-Click Copy Product Info
|
C25-140 is a small molecule compound that inhibits TRAF6-Ubc13 interaction. C25-140 can directly bind to the E3 ligase TNF receptor-associated factor 6 (TRAF6), thereby blocking the interaction between TRAF6 and Ubc13 and thus reducing the activity of TRAF6.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1358099-18-9
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
C25-140 is a small molecule compound that inhibits TRAF6-Ubc13 interaction. C25-140 can directly bind to the E3 ligase TNF receptor-associated factor 6 (TRAF6), thereby blocking the interaction between TRAF6 and Ubc13 and thus reducing the activity of TRAF6[1]. TRAF6 acts as a key regulator that bridges innate immunity, proinflammatory cytokines and antigen receptors to the canonical NF-κB pathway[2]. Ubc13 is a ubiquitin-conjugating enzyme E2 that also plays a key role in the activation of the NF-κB signaling pathway and plays a role in the development of inflammatory diseases and cancer[3]. C25-140 can block NF-κB activation in various immune and inflammatory signaling pathways in primary human and mouse cells[4].
In vitro, pretreatment of H9C2 cardiomyocytes with C25-140 (5μM) for 2h inhibited the expression of Bax and caspase3 in lipopolysaccharide (LPS)-induced cells and reduced the expression of Bcl2[5].
In vivo, C25-140 (5mg/kg) was intraperitoneally injected into mice with acute kidney injury (AKI) induced by diquat (DQ) poisoning for 7 days, which regulated the Toll-like receptor 4 (TLR4)/TRAF6/NF-κB signaling pathway, downregulated the levels of inflammatory cytokines IL-1β, IL-6 and TNF-α, and alleviated the symptoms of acute kidney injury in mice[6]. C25-140 (10μM, 20μM, 30μM) was intravenously injected into mice with cerebral hemorrhage, which alleviated neurological deficits after cerebral hemorrhage, reduced brain edema, and reduced the expression of pyroptotic inflammasomes such as GSDMD, NLRP3 and ASC in brain tissue[7].
References:
[1] Li J, Liu N, Tang L, et al. The relationship between TRAF6 and tumors[J]. Cancer Cell International, 2020, 20(1): 429.
[2] Häcker H, Tseng P H, Karin M. Expanding TRAF function: TRAF3 as a tri-faced immune regulator[J]. Nature Reviews Immunology, 2011, 11(7): 457-468.
[3] Zhang H, Hu H, Greeley N, et al. STAT3 restrains RANK-and TLR4-mediated signalling by suppressing expression of the E2 ubiquitin-conjugating enzyme Ubc13[J]. Nature communications, 2014, 5(1): 5798.
[4] Brenke J K, Popowicz G M, Schorpp K, et al. Targeting TRAF6 E3 ligase activity with a small-molecule inhibitor combats autoimmunity[J]. Journal of Biological Chemistry, 2018, 293(34): 13191-13203.
[5] Li Y, Zhang L, Zhang P, et al. Dehydrocorydaline protects against sepsis-induced myocardial injury through modulating the TRAF6/NF-κB pathway[J]. Frontiers in pharmacology, 2021, 12: 709604.
[6] Huang T, Rao G, Zhao Z, et al. Protective effect of tumor necrosis factor receptor-associated factor 6 inhibitor C25-140 on acute kidney injury induced by diquat poisoning in mice[J]. Zhonghua wei zhong bing ji jiu yi xue, 2024, 36(12): 1273-1278.
[7] HU Q, ZENG H, FENG C, et al. Inhibition of TRAF6 alleviates secondary brain injury by reducing neuronal pyroptosis after intracerebral hemorrhage[J]. Experimental Animals, 2024: 24-0078.
| Cell experiment [1]: | |
Cell lines | H9C2 cardiomyocytes |
Preparation Method | The H9C2 cardiomyocytes were pretreated with C25-140 (5μM) for 2h and then treated with LPS (10μg/mL) and dehydrocorydaline (Deh) (10μg/mL) for 24h. Western blot was performed for the detection of Bax, Caspase3 and Bcl2 expressions in cardiomyocytes. |
Reaction Conditions | 5μM; 2h |
Applications | C25-140 inhibited Bax and Caspase3 expression and decreased Bcl2 expression in LPS-induced cells. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | A total of 80 SPF grade healthy male C57BL/6 mice were randomly divided into the normal control group, Diquat (DQ) model group, C25-140 intervention group, and C25-140 control group, with 20 mice in each group. The DQ poisoning mouse model was established by using one-time intraperitoneal injection of 1mL of 40mg/kg DQ solution. The normal control group and C25-140 control group were injected with an equal amount of pure water into the peritoneal cavity. After 4h of model establishment, the C25-140 intervention group and C25-140 control group were given intraperitoneal injection of C25-140 5mg/kg. The normal control group and DQ model group were given equal amounts of pure water, once a day for 7 consecutive days. After 7 days, the mice were anesthetized, eye blood was collected, and renal tissue was collected after sacrifice. The pathological changes of renal tissue were observed under a light microscope and renal tissue structure and mitochondrial changes were observed under transmission electron microscopy. The levels of serum creatinine (SCr) and blood urea nitrogen (BUN) were measured. ELISA was used to measure the levels of serum interleukins (IL-6, IL-1β) and TNF-α. Western blotting was used to detect the protein expression levels of TRAF6, myeloid differentiation factor 88 (MyD88), and nuclear NF-κB in renal tissue. Chemical method was used to determine the content of serum MDA and SOD. |
Dosage form | 5mg/kg; 7 days; i.p. |
Applications | TRAF6 inhibitor C25-140 can alleviate acute kidney injury (AKI) induced by DQ poisoning in mice by regulating the Toll-like receptor 4 (TLR4)/TRAF6/NF-κB signaling pathway and downregulating the levels of inflammatory cytokines IL-1β, IL-6, and TNF-α. |
References: | |
| Cas No. | 1358099-18-9 | SDF | |
| Canonical SMILES | O=C(N1CCC(CC2=CC=CC=C2)CC1)CCC3=C(C)N(C4=NN5C(C=C4)=NN=C5C)N=C3C | ||
| Formula | C26H31N7O | M.Wt | 457.57 |
| Solubility | DMSO : ≥ 130 mg/mL (284.11 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.1855 mL | 10.9273 mL | 21.8546 mL |
| 5 mM | 437.1 μL | 2.1855 mL | 4.3709 mL |
| 10 mM | 218.5 μL | 1.0927 mL | 2.1855 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)