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| 10mg |
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Purity: ≥98%
Apremilast (also known as CC-10004), a thalidomide analog, is a novel and orally bioavailable small molecule inhibitor of the phosphodiesterase 4 (PDE4) with potential anti-inflammatory activity. It regulates inflammation through multiple cAMP downstream effectors. Apremilast inhibits PDE4 with an IC50 of 74 nM using 1 μM cAMP as substrate. Apremilast inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. Apremilast was approved by the FDA in 2014 for treatment of adults with active psoriatic arthritis. It is also being tested for its efficacy in treating other chronic inflammatory diseases such as ankylosing spondylitis, Behcet's disease, and rheumatoid arthritis.
| ln Vitro |
Apremilast (CC-10004) has an IC50 of 104 nM (pIC50=6.98±0.2) that inhibits TNF-α release by lipopolysaccharide (LPS). This is similar to the potency of Apremilast for PDE4 enzymatic inhibition (IC50=74 nM) and nearly exactly replicates the TNF-α inhibition that Apremilast has previously been shown to inhibit on peripheral blood mononuclear cells (PBMCs) (IC50=110 nM). With increased intracellular cAMP levels, apremilast suppresses TNF-α, and these results convincingly support this theory. Apremilast-induced IL-10 activation and TNF-α suppression were not observed in the presence of PKA, Epac1, or Epac2 knockdowns].
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| ln Vivo |
When taken orally at a dose of 5 mg/kg, apremilast (CC-10004) dramatically reduces the amount of TNF-α produced in the air pouch by 39% (61±6% of the vehicle, P <0.001) and decreases the number of leukocytes by 28% (72±12% of the vehicle, P <0.05). Immunohistologic investigation confirms that Apremilast significantly reduces neutrophil accumulation in the air pouch membrane. Both methotrexate (MTX) and apremilast considerably decrease leukocyte infiltration in the murine air pouch model, however only apremilast significantly inhibits TNF-α release. There is no greater suppression of leukocyte infiltration or TNF-α release when MTX (1 mg/kg) is added to Apremilast (5 mg/kg) than when Apremilast is used alone[1]. It has been demonstrated that the new oral PDE4 inhibitor apremilast controls inflammatory mediators. The mean maximum plasma concentration (Cmax) following oral administration of Apremilast is determined to be 67.00±14.87 ng/mL. Apremilast's plasma concentration drops quickly, and it eventually disappears from plasma with a terminal half-life of 0.92±0.46 h[2].
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| References |
[1]. Perez-Aso M, et al. Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors. Arthritis Res Ther. 2015 Sep 15;17:249.
[2]. Chen LG, et al. Determination of Apremilast in Rat Plasma by UPLC-MS-MS and Its Application to a Pharmacokinetic Study. J Chromatogr Sci. 2016 Sep;54(8):1336-40 |
| Molecular Formula |
C22H24N2O7S
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|---|---|
| Molecular Weight |
460.50
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| CAS # |
608141-41-9
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| Related CAS # |
Apremilast-d5;1258597-47-5;(R)-Apremilast;608141-44-2;(Rac)-Apremilast-d5;1258597-61-3
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| SMILES |
CC(NC1=CC=CC(C(N2[C@@H](C3=CC=C(OC)C(OCC)=C3)CS(=O)(C)=O)=O)=C1C2=O)=O
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| Chemical Name |
(S)-N-(2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide
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| Synonyms |
CC-10004; CC10004; Apremilast; CC 10004; Otezla (Trade name)
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.43 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 5 mg/mL (10.86 mM) in 0.5% CMC-Na 0.5% Tween-80 (add these co-solvents sequentially from left to right, and one by one), Suspened solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1716 mL | 10.8578 mL | 21.7155 mL | |
| 5 mM | 0.4343 mL | 2.1716 mL | 4.3431 mL | |
| 10 mM | 0.2172 mL | 1.0858 mL | 2.1716 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT06324435 | Not yet recruiting NEW | Drug: Apremilast | Alcohol Use Disorder | Yale University | April 15, 2024 | Phase 1 |
| NCT03656666 | Active, not recruiting | Drug: Apremilast Drug: Placebo | Lichen Planus of Vulva Female Genital Disease |
Oslo University Hospita | September 24, 2019 | Phase 2 |
| NCT04804553 | Recruiting | Drug: Apremilast Drug: Placebo | Active Juvenile Psoriatic Arthritis | Amgen | March 17, 2022 | Phase 3 |
| NCT04528082 | Recruiting | Drug: Apremilast Drug: Placebo | Behçet Disease | Amgen | September 9, 2021 | Phase 3 |
Apremilast and methotrexate (MTX) prevent inflammation in the air pouch independently.Arthritis Res Ther.2015 Sep 15;17:249. |
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Apremilast inhibits lipopolysaccharide (LPS)-induced TNF-α release via cyclic adenosine monophosphalphate (cAMP).Arthritis Res Ther.2015 Sep 15;17:249. |
Effect of Protein kinase A (PKA), Exchange protein directly activated by cAMP (Epac)1 and Epac2 knockdown on the action of apremilast.Arthritis Res Ther.2015 Sep 15;17:249. |
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