BI-78D3 functions as a substrate competitive inhibitor ofJNK, inhibit theJNKkinase activity (IC₅₀=280 nM).

BI-78D3, dose-dependently inhibits the phosphorylation of JNK substrates both in vitro and in cell. BI-78D3 is able to compete with the D-domain of JIP1 (amino acids 153-163; pepJIP1) for JNK1 binding (IC₅₀=500 nM). Using the same in vitro LanthaScreen kinase assay and the same ATF2 substrate, BI-78D3 is found to be 100-fold less active vs. p38α, a member of the MAPK family with high structural similarity to JNK, and completely inactive against mTOR and PI3-kinase (α-isoform), both unrelated protein kinases. Furthermore, Lineweaver-Burk analysis clearly indicates that BI-78D3 is competitive with ATF2 for binding to JNK1 with an apparent K_ivalue of 200 nM. In an attempt to profile the properties of BI-78D3 in the context of a complex cellular milieu, the cell-based LanthaScreen kinase assay is used. In this assay BI-78D3 is able to inhibit TNF-α stimulated phosphorylation of c-Jun in cell (EC₅₀=12.4 μM)^[1].

The link between ConA-induced liver failure, TNF receptor signaling, and JNK function has been established by studies employing JNK1^-/-and JNK2^-/-mice. For this analysis, insulin insensitive mice are injected only once with 25 mg/kg BI-78D3, 30 min before insulin injection. The effect of insulin on blood glucose levels is then measured. BI-78D3 results in a statistically significant reduction in blood glucose levels as compared with the vehicle control. Thus, the ability of BI-78D3 to abrogate ConA-induced liver damage and restore insulin sensitivity is consistent with its proposed function as an effective JNK inhibitor. Liquid chromatography/mass spectrometry bio-availability analysis demonstrates that BI-78D3 has favorable microsome and plasma stability (T_1/2=54 min)^[1].

379.37

Solid

C₁₃H₉N₅O₅S₂

883065-90-5

Room temperature in continental US; may vary elsewhere.

DMSO : 100 mg/mL(263.59 mM;Need ultrasonic)

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。

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: ≥ 2.5 mg/mL (6.59 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.59 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 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。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: ≥ 2.5 mg/mL (6.59 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.59 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 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。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明