C25-140 是一种首创的,具有口服活性和一定选择性的
TRAF6-Ubc13相互作用的抑制剂,直接与 TRAF6 结合,阻断 TRAF6 和 Ubc13 的相互作用,从而降低 TRAF6 活性,降低
NF-κB的活性,并对抗自身免疫。
生物活性 |
C25-140, a first-in-class, orally active, and fairly selectiveTRAF6-Ubc13inhibitor, directly binds to TRAF6, and blocks the interaction of TRAF6 with Ubc13. C25-140 lowers TRAF6 activity, reducesNF-κBactivation, and combats autoimmunity[1].
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IC50& Target |
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体外研究 (In Vitro) |
C25-140 dose-dependently impedes TRAF6-Ubc13 interaction[1]. C25-140 (10-30 μM; 2 hours) effectively reduces TRAF6-mediated ubiquitin chain formation[1]. C25-140 affects TNFα-induced phosphorylation of IκBα as well as NF-κB-induced target gene expression[1]. C25-140 efficiently inhibits IL-1β- and TNFα-mediated receptor signaling in the context of cytokine activation[1].
Western Blot Analysis[1]
Cell Line: |
TRAF6WT |
Concentration: |
10 μM, 20 μM, 30 μM |
Incubation Time: |
2 hours |
Result: |
Effectively reduced TRAF6-mediated ubiquitin chain formation. |
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体内研究 (In Vivo) |
C25-140 (~1.5 mg/kg; topically to the shaved back and the right ear; twice daily for 6 days) ameliorates symptoms of autoimmune psoriasis in R 837-induced psoriasis mouse model[1]. C25-140 (6-14 mg/kg; given i.p.; twice daily for 14 days) shows a dose-dependent improvement of RA disease outcome in Collagen-induced arthritis (CIA) model[1]. C25-140 (10 mg/kg; i.v.) treatment shows that the Cmax, AUC, t1/2and Vdare 9.7 μg/mL, 274083 ng min/mL, 80.62 min, and 4.13 L/kg, respectively[1]. . C25-140 (10 mg/kg; p.o.) treatment shows that the Cmax, AUC, t1/2and Vdare 3.4 μg/mL, 124034 ng min/mL, 127.33 min and 13.3 L/kg, respectively[1]. C25-140 (10 mg/kg; i.p.) treatment shows that the Cmax, AUC, t1/2and Vdare 4.2μg/mL, 100000 ng min/mL, 184 min, 25.6 L/kg, respectively[1].
Animal Model: |
R 837-induced psoriasis mouse model (male BALB/c mice)[1] |
Dosage: |
~1.5 mg/kg |
Administration: |
Topically to the shaved back and the right ear; twice daily for 6 days |
Result: |
Showed a dose-dependent improvement of RA disease outcome. |
Animal Model: |
Collagen-induced arthritis (CIA) model in DBA1/J mice[1] |
Dosage: |
6 mg/kg, 10 mg/kg, 14 mg/kg |
Administration: |
Given i.p.; twice daily for 14 days |
Result: |
Ameliorated the arthritic index to almost baseline levels in this efficacy model at doses of 10 and 14 mg/kg. Dose-dependently improved symptoms of RA including inflammation and structural damage. |
Animal Model: |
BALB/C mice[1] |
Dosage: |
10 mg/kg |
Administration: |
I.v. (Pharmacokinetic Analysis) |
Result: |
The Cmax, AUC, t1/2and Vdwere 9.7 μg/mL, 274083 ng min/mL, 80.62 min, and 4.13 L/kg, respectively. |
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分子量 |
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性状 |
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Formula |
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CAS 号 |
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运输条件 |
Room temperature in continental US; may vary elsewhere.
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储存方式 |
Powder |
-20°C |
3 years |
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4°C |
2 years |
In solvent |
-80°C |
6 months |
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-20°C |
1 month |
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溶解性数据 |
In Vitro:
DMSO : 41.67 mg/mL(91.07 mM;Need ultrasonic)
配制储备液
1 mM |
2.1855 mL |
10.9273 mL |
21.8546 mL |
5 mM |
0.4371 mL |
2.1855 mL |
4.3709 mL |
10 mM |
0.2185 mL |
1.0927 mL |
2.1855 mL |
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请根据半岛bd体育手机客户端 在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的半岛bd体育手机客户端 失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。
In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂:
——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶
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1.
请依序添加每种溶剂: 10% DMSO40%PEG3005%Tween-8045% saline
Solubility: ≥ 2.08 mg/mL (4.55 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.55 mM,饱和度未知) 的澄清溶液。
以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。
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2.
请依序添加每种溶剂: 10% DMSO90% (20%SBE-β-CDin saline)
Solubility: ≥ 2.08 mg/mL (4.55 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.55 mM,饱和度未知) 的澄清溶液。
以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。
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3.
请依序添加每种溶剂: 10% DMSO90%corn oil
Solubility: ≥ 2.08 mg/mL (4.55 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.55 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。
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以上所有助溶剂都可在本网站选购。
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