Apremilast
[CAS# 608141-41-9]

Identification

• Classification: Biochemical >> Inhibitor >> Metabolism >> PDE inhibitor
• Name: Apremilast
• Synonyms: CC 10004; (S)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione; (S)-N-(2-(1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide
• Molecular Formula: C₂₂H₂₄N₂O₇S
• Molecular Weight: 460.50
• CAS Registry Number: 608141-41-9
• EC Number: 807-237-6
• SMILES: CCOC1=C(C=CC(=C1)[C@@H](CS(=O)(=O)C)N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)C)OC

Properties

• Solubility: 45 mg/mL (DMSO)
• Density: 1.381

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Risk Statements: H302-H312-H332-H360-H361-H361fd-H362-H372
• Safety Statements: P203-P260-P261-P263-P264-P270-P271-P280-P301+P317-P302+P352-P304+P340-P317-P318-P319-P321-P330-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H312
Reproductive toxicity	Repr.	1A	H360
Reproductive toxicity	Lact.	-	H362

Discovery and Applications

Apremilast is a novel oral medication used primarily in the treatment of inflammatory conditions such as psoriasis and psoriatic arthritis. Discovered and developed in the early 2000s, it represents a significant advancement in the management of chronic inflammatory diseases due to its targeted mechanism of action and favorable safety profile.

Apremilast functions as a selective inhibitor of phosphodiesterase 4 (PDE4), an enzyme involved in the regulation of inflammatory and immune responses. By inhibiting PDE4, apremilast increases intracellular levels of cyclic adenosine monophosphate (cAMP), which in turn modulates the activity of various inflammatory mediators. This action helps to reduce the inflammatory process that contributes to conditions like psoriasis and psoriatic arthritis.

The discovery of apremilast emerged from research focused on finding new treatments for chronic inflammatory diseases. Unlike traditional therapies that may broadly suppress the immune system, apremilast offers a more targeted approach by specifically affecting the PDE4 pathway. This targeted mechanism helps to mitigate inflammation and improve symptoms while minimizing some of the systemic side effects associated with other treatments.

Apremilast is used primarily for managing moderate to severe plaque psoriasis and active psoriatic arthritis. In the case of psoriasis, it helps reduce the number and severity of skin plaques, as well as alleviate associated symptoms such as itching and scaling. For psoriatic arthritis, apremilast reduces joint pain, swelling, and stiffness, improving physical function and quality of life for affected individuals.

Administered orally in tablet form, apremilast is typically taken twice daily. The dosing regimen may be adjusted based on the patient's response and tolerability. Clinical studies have demonstrated that apremilast is effective in improving symptoms of psoriasis and psoriatic arthritis, providing significant benefits for patients who have not responded adequately to other treatments.

One of the advantages of apremilast is its favorable safety profile compared to some other immunomodulatory drugs. Common side effects include gastrointestinal symptoms such as diarrhea, nausea, and abdominal pain, but these are generally manageable and often decrease with continued use. Unlike some systemic treatments, apremilast does not require regular blood monitoring, making it a more convenient option for long-term management.

In summary, apremilast represents an important advancement in the treatment of chronic inflammatory conditions such as psoriasis and psoriatic arthritis. Its selective inhibition of PDE4 provides a targeted approach to reducing inflammation, offering a valuable option for patients who require effective and well-tolerated therapy.

References

2019. Systemic Treatment of Psoriasis with JAK Inhibitors: A Review. Dermatology and Therapy, 9(4).
DOI: 10.1007/s13555-019-00347-w

2012. Oral apremilast in the treatment of active psoriatic arthritis: Results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis and Rheumatism, 64(10).
DOI: 10.1002/art.34627

2021. Real-World Experience of Patient-Relevant Benefits and Treatment Satisfaction with Apremilast in Patients with Psoriasis: An Analysis of the APPRECIATE Study. Dermatology and Therapy, 11(6).
DOI: 10.1007/s13555-021-00628-3