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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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].
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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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -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 |
*请根据产品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产品失效。
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 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (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。 3. 请依序添加每种溶剂： 10% DMSO 90%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。 *以上所有助溶剂都可在本网站选购。
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