Apremilast
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MedKoo CAT#: 205894

CAS#: 608141-41-9

Description: Apremilast, also known as CC-10004, is a thalidomide analog and is an orally available small molecule inhibitor of phosphodiesterase 4 (PDE4). Apremilast specifically inhibits PDE4 and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. It has anti-inflammatory activity. Apremilast was approved by the USFDA in March 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.

Chemical Structure

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Apremilast
CAS# 608141-41-9
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 205894
Name: Apremilast
CAS#: 608141-41-9
Chemical Formula: C22H24N2O7S
Exact Mass: 460.13
Molecular Weight: 460.500
Elemental Analysis: C, 57.38; H, 5.25; N, 6.08; O, 24.32; S, 6.96

Price and Availability

Size Price Availability Quantity
200mg USD 150 Ready to ship
500mg USD 250 Ready to ship
1g USD 450 Ready to ship
2g USD 750 Ready to ship
5g USD 1450 Ready to ship
10g USD 1950 Ready to ship
20g USD 3250 Ready to ship
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Synonym: CC10004; CC-10004; CC 10004; Apremilast; brand name: Otezla.

IUPAC/Chemical Name: (S)-N-(2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide

InChi Key: IMOZEMNVLZVGJZ-QGZVFWFLSA-N

InChi Code: InChI=1S/C22H24N2O7S/c1-5-31-19-11-14(9-10-18(19)30-3)17(12-32(4,28)29)24-21(26)15-7-6-8-16(23-13(2)25)20(15)22(24)27/h6-11,17H,5,12H2,1-4H3,(H,23,25)/t17-/m1/s1

SMILES Code: CC(NC1=CC=CC(C(N2[C@@H](C3=CC=C(OC)C(OCC)=C3)CS(=O)(C)=O)=O)=C1C2=O)=O

Appearance: White to off-white powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Apremilast (CC-10004) is an inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4) with an IC50 of 74 nM. Apremilast inhibits TNF-α release by lipopolysaccharide (LPS) with an IC50 of 104 nM.
In vitro activity: Here, apremilast significantly decreased the expression of LOX-1, suggesting an inhibitory effect against foam cell formation. Proinflammatory cytokines are a major effector of atherogenesis. Inhibition of PDE4 by drugs including apremilast is known to suppress the expression of TNF-α. Apremilast has been shown to inhibit the expression of these three cytokines. Here, apremilast significantly decreased ox-LDL-induced TNF-α, IL-6, and IL-8 expression, however, whether these pathways were involved remains unclear. Reference: Aging (Albany NY). 2020 Oct 15; 12(19): 19012–19021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732304/
In vivo activity: Apremilast (2.5 and 5 mg/kg twice daily) significantly reduced ear swelling in two models of dermatitis (Fig. 3). In the FITC model, ear thickness significantly (P < 0.05) increased from 0.19 ± 0.00 mm (baseline) to 0.50 ± 0.02 mm (day 13) in vehicle-treated mice. Dexamethasone 1 mg/kg significantly reduced ear thickness to 0.34 ± 0.01 mm on days 11–13 compared with vehicle-treated mice (P < 0.05). Similarly, apremilast 2.5 and 5 mg/kg significantly reduced ear thickness to 0.40 ± 0.01 mm and 0.41 ± 0.01 mm, respectively, on days 11–13 compared with vehicle-treated mice (P < 0.05). MCP-1 protein levels in the inflamed ear were 184.21 ± 32.54 pg/mg in vehicle-treated mice. Apremilast significantly reduced MCP-1 protein levels to 87.58 ± 18.04 pg/mg compared with vehicle (P < 0.05). There were trends toward a decrease by apremilast of IL-4, IL-10, IL-13, IL-17A, and IL-12/23p40 protein levels in the inflamed ears (Fig. 4). Reference: Drugs R D. 2019 Dec; 19(4): 329–338. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890576/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 48.7 105.69
Ethanol 3.0 6.51
DMF 20.0 43.43
DMF:PBS (pH 7.2) (1:1) 0.5 1.09

Preparing Stock Solutions

The following data is based on the product molecular weight 460.50 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Wang H, Yang G, Zhang Q, Liang X, Liu Y, Gao M, Guo Y, Chen L. Apremilast ameliorates ox-LDL-induced endothelial dysfunction mediated by KLF6. Aging (Albany NY). 2020 Oct 14;12(19):19012-19021. doi: 10.18632/aging.103665. Epub ahead of print. PMID: 33052879; PMCID: PMC7732304. 2. Kragstrup TW, Adams M, Lomholt S, Nielsen MA, Heftdal LD, Schafer P, Deleuran B. IL-12/IL-23p40 identified as a downstream target of apremilast in ex vivo models of arthritis. Ther Adv Musculoskelet Dis. 2019 Feb 22;11:1759720X19828669. doi: 10.1177/1759720X19828669. PMID: 30833991; PMCID: PMC6391542. 3. Schafer PH, Adams M, Horan G, Truzzi F, Marconi A, Pincelli C. Apremilast Normalizes Gene Expression of Inflammatory Mediators in Human Keratinocytes and Reduces Antigen-Induced Atopic Dermatitis in Mice. Drugs R D. 2019 Dec;19(4):329-338. doi: 10.1007/s40268-019-00284-1. PMID: 31598889; PMCID: PMC6890576. 4. Perez-Aso M, Montesinos MC, Mediero A, Wilder T, Schafer PH, Cronstein B. Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors. Arthritis Res Ther. 2015 Sep 15;17(1):249. doi: 10.1186/s13075-015-0771-6. PMID: 26370839; PMCID: PMC4570588.
In vitro protocol: 1. Wang H, Yang G, Zhang Q, Liang X, Liu Y, Gao M, Guo Y, Chen L. Apremilast ameliorates ox-LDL-induced endothelial dysfunction mediated by KLF6. Aging (Albany NY). 2020 Oct 14;12(19):19012-19021. doi: 10.18632/aging.103665. Epub ahead of print. PMID: 33052879; PMCID: PMC7732304. 2. Kragstrup TW, Adams M, Lomholt S, Nielsen MA, Heftdal LD, Schafer P, Deleuran B. IL-12/IL-23p40 identified as a downstream target of apremilast in ex vivo models of arthritis. Ther Adv Musculoskelet Dis. 2019 Feb 22;11:1759720X19828669. doi: 10.1177/1759720X19828669. PMID: 30833991; PMCID: PMC6391542.
In vivo protocol: 1. Schafer PH, Adams M, Horan G, Truzzi F, Marconi A, Pincelli C. Apremilast Normalizes Gene Expression of Inflammatory Mediators in Human Keratinocytes and Reduces Antigen-Induced Atopic Dermatitis in Mice. Drugs R D. 2019 Dec;19(4):329-338. doi: 10.1007/s40268-019-00284-1. PMID: 31598889; PMCID: PMC6890576. 2. Perez-Aso M, Montesinos MC, Mediero A, Wilder T, Schafer PH, Cronstein B. Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors. Arthritis Res Ther. 2015 Sep 15;17(1):249. doi: 10.1186/s13075-015-0771-6. PMID: 26370839; PMCID: PMC4570588.

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1: Nassim D, Alajmi A, Jfri A, Pehr K. Apremilast in dermatology: A review of literature. Dermatol Ther. 2020 Nov;33(6):e14261. doi: 10.1111/dth.14261. Epub 2020 Sep 27. PMID: 32876993.


2: Strober B, Thaçi D, Sofen H, Kircik L, Gordon KB, Foley P, Rich P, Paul C, Bagel J, Colston E, Throup J, Kundu S, Sekaran C, Linaberry M, Banerjee S, Papp KA. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double- blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol. 2023 Jan;88(1):40-51. doi: 10.1016/j.jaad.2022.08.061. Epub 2022 Sep 14. PMID: 36115523.


3: Carrascosa JM, Del-Alcazar E. Apremilast for psoriasis treatment. G Ital Dermatol Venereol. 2020 Aug;155(4):421-433. doi: 10.23736/S0392-0488.20.06684-5. Epub 2020 Jun 15. PMID: 32545946.


4: Keating GM. Apremilast: A Review in Psoriasis and Psoriatic Arthritis. Drugs. 2017 Mar;77(4):459-472. doi: 10.1007/s40265-017-0709-1. PMID: 28213862.


5: Maloney NJ, Zhao J, Tegtmeyer K, Lee EY, Cheng K. Off-label studies on apremilast in dermatology: a review. J Dermatolog Treat. 2020 Mar;31(2):131-140. doi: 10.1080/09546634.2019.1589641. Epub 2019 Apr 2. PMID: 30935262; PMCID: PMC6774908.


6: Hatemi G, Mahr A, Ishigatsubo Y, Song YW, Takeno M, Kim D, Melikoğlu M, Cheng S, McCue S, Paris M, Chen M, Yazici Y. Trial of Apremilast for Oral Ulcers in Behçet's Syndrome. N Engl J Med. 2019 Nov 14;381(20):1918-1928. doi: 10.1056/NEJMoa1816594. PMID: 31722152.


7: Stein Gold L, Papp K, Pariser D, Green L, Bhatia N, Sofen H, Albrecht L, Gooderham M, Chen M, Paris M, Wang Y, Callis Duffin K. Efficacy and safety of apremilast in patients with mild-to-moderate plaque psoriasis: Results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2022 Jan;86(1):77-85. doi: 10.1016/j.jaad.2021.07.040. Epub 2021 Jul 31. PMID: 34343599.


8: Sandhu VK, Eder L, Yeung J. Apremilast and its role in psoriatic arthritis. G Ital Dermatol Venereol. 2020 Aug;155(4):386-399. doi: 10.23736/S0392-0488.20.06640-7. PMID: 33050680.


9: Papp K, Reich K, Leonardi CL, Kircik L, Chimenti S, Langley RG, Hu C, Stevens RM, Day RM, Gordon KB, Korman NJ, Griffiths CE. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015 Jul;73(1):37-49. doi: 10.1016/j.jaad.2015.03.049. PMID: 26089047.


10: Hathaway NE, Lyford WH. Apremilast Uses and Relevance to the Military. Cutis. 2021 Apr;107(4):216-220. doi: 10.12788/cutis.0231. PMID: 34096849.


11: Bitar C, Ninh T, Brag K, Foutouhi S, Radosta S, Meyers J, Baddoo M, Liu D, Stumpf B, Harms PW, Saba NS, Boh E. Apremilast in Recalcitrant Cutaneous Dermatomyositis: A Nonrandomized Controlled Trial. JAMA Dermatol. 2022 Dec 1;158(12):1357-1366. doi: 10.1001/jamadermatol.2022.3917. PMID: 36197661; PMCID: PMC9535502.


12: Chimenti MS, Gramiccia T, Saraceno R, Bianchi L, Garofalo V, Buonomo O, Perricone R, Chimenti S, Chiricozzi A. Apremilast for the treatment of psoriasis. Expert Opin Pharmacother. 2015;16(13):2083-94. doi: 10.1517/14656566.2015.1076794. Epub 2015 Aug 4. PMID: 26243735.


13: Otto M, Dorn B, Grasmik T, Doll M, Meissner M, Jakob T, Hrgovic I. Apremilast effectively inhibits TNFα-induced vascular inflammation in human endothelial cells. J Eur Acad Dermatol Venereol. 2022 Feb;36(2):237-246. doi: 10.1111/jdv.17769. Epub 2021 Nov 13. PMID: 34699634.


14: Chen Y, Li Z, Li H, Su W, Xie Y, Pan Y, Chen X, Liang D. Apremilast Regulates the Teff/Treg Balance to Ameliorate Uveitis via PI3K/AKT/FoxO1 Signaling Pathway. Front Immunol. 2020 Nov 17;11:581673. doi: 10.3389/fimmu.2020.581673. PMID: 33281814; PMCID: PMC7705241.


15: Deeks ED. Apremilast: A Review in Oral Ulcers of Behçet's Disease. Drugs. 2020 Feb;80(2):181-188. doi: 10.1007/s40265-019-01253-3. PMID: 31933168.


16: Mehta H, Sharma A, Dogra S. Evolving utility of apremilast in dermatological disorders for off-label indications. Clin Exp Dermatol. 2022 Dec;47(12):2136-2149. doi: 10.1111/ced.15377. Epub 2022 Oct 8. PMID: 35974705.


17: Carrascosa JM, Belinchón I, Rivera R, Ara M, Bustinduy M, Herranz P. The Use of Apremilast in Psoriasis: A Delphi Study. Actas Dermosifiliogr (Engl Ed). 2020 Mar;111(2):115-134. English, Spanish. doi: 10.1016/j.ad.2019.07.005. Epub 2019 Dec 19. PMID: 31864537.


18: Schett G. Apremilast in psoriatic arthritis. Clin Exp Rheumatol. 2015 Sep- Oct;33(5 Suppl 93):S98-100. Epub 2015 Oct 15. PMID: 26472278.


19: Poole RM, Ballantyne AD. Apremilast: first global approval. Drugs. 2014 May;74(7):825-37. doi: 10.1007/s40265-014-0218-4. PMID: 24797159.


20: Shutty B, West C, Pellerin M, Feldman S. Apremilast as a treatment for psoriasis. Expert Opin Pharmacother. 2012 Aug;13(12):1761-70. doi: 10.1517/14656566.2012.699959. Epub 2012 Jun 20. PMID: 22712800.