Apremilast (CC-10004) is an orally available inhibitor of type-4 cyclic nucleotidephosphodiesterase(PDE-4) with anIC₅₀of 74 nM. Apremilast inhibits TNF-α release by lipopolysaccharide (LPS) with an IC₅₀of 104 nM^[1].

Apremilast (CC-10004) inhibits TNF-α release by lipopolysaccharide (LPS) with an IC₅₀of 104 nM (pIC₅₀=6.98±0.2), which almost exactly replicates previous reported TNF-α inhibition by Apremilast on peripheral blood mononuclear cells (PBMCs) (IC₅₀=110 nM) and which is similar to the potency of Apremilast for PDE4 enzymatic inhibition (IC₅₀=74 nM). These results are clearly consistent with the hypothesis that Apremilast inhibits TNF-α by increasing intracellular cAMP levels. PKA, Epac1 and Epac2 knockdowns prevented TNF-α inhibition and IL-10 stimulation by Apremilast^[1].

Apremilast (CC-10004), orally administered (5 mg/kg), significantly inhibits TNF-α production in the air pouch by 39 % (61±6 % of vehicle, P<0.001) and diminishes (by 28 %) the number of leukocytes present (72±12 % of vehicle, P<0.05). In agreement, immunohistologic analysis shows that neutrophil accumulation in the air pouch membrane is dramatically reduced by Apremilast. In the murine air pouch model, both Apremilast and methotrexate (MTX) significantly inhibit leukocyte infiltration, while Apremilast, but not MTX, significantly inhibits TNF-α release. The addition of MTX (1 mg/kg) to Apremilast (5 mg/kg) yields no more inhibition of leukocyte infiltration or TNF-α release than with Apremilast alone^[1].
Apremilast is a novel, oral PDE4 inhibitor that has been shown to regulate inflammatory mediators. After oral administration of Apremilast, a mean maximum plasma concentration (C_max) is found to be 67.00±14.87 ng/mL. The plasma concentration of Apremilast decreases rapidly and is eliminated from plasma with a terminal half-life of 0.92±0.46 h^[2]

460.50

Solid

C₂₂H₂₄N₂O₇S

608141-41-9

阿普司特

Room temperature in continental US; may vary elsewhere.

DMSO : 44 mg/mL(95.55 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： 0.5%CMC-Na  0.5%Tween-80

  Solubility: 5 mg/mL (10.86 mM); Suspened solution; Need ultrasonic
• 2.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (5.43 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.43 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
• 3.

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

  Solubility: 2.5 mg/mL (5.43 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (5.43 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  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
• 4.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (5.43 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.43 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。