Crisaborole, sold under the brand name Eucrisa among others, is a

nonsteroidal A nonsteroidal compound is a drug that is not a steroid nor a steroid derivative. Nonsteroidal anti-inflammatory drugs (NSAIDs) are distinguished from corticosteroids as a class of anti-inflammatory agents. List of nonsteroidal steroid receptor mo ...

topical medication A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surface area, body surfaces such as the skin or mucous membranes to treat ailments via a large ...

used for the treatment of mild-to-moderate

atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin. Atopic dermatitis is also often called simply eczema but the same term is also used to refer to dermatitis, the larger group of skin conditi ...

(eczema) in adults and children. The most common side effects are reactions at the application site (including burning or stinging). Crisaborole is a phosphodiesterase 4 (PDE-4) inhibitor, although its specific mechanism of action in atopic dermatitis is not known.

Side effects

At the site of application, crisaborole may cause burning or stinging. Rarely, there may be an

allergic reaction Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...

Medical uses

In the US, crisaborole is indicated for topical treatment of mild to moderate atopic dermatitis in people three months of age and older. In the EU, crisaborole was authorized for treatment of mild to moderate atopic dermatitis in people two years of age and older with ≤ 40% body surface area (BSA) affected.

Pharmacology

Pharmacodynamics

Crisaborole is a

phosphodiesterase-4 inhibitor A phosphodiesterase-4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). It is a member of the larger family of PDE inhibito ...

, mainly acting on phosphodiesterase 4B (PDE4B), which causes inflammation. Chemically, crisaborole is a phenoxybenzoxaborole. Inhibition of PDE4B appears to suppress the release of

tumor necrosis factor alpha Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...

(TNFα),

interleukin-12 Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, helper T cells and human B- lymphoblastoid cells ( NC-37) in response to antigenic stimulation. IL-12 belongs to the family of i ...

(IL-12), IL-23 and other

cytokines Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

, proteins believed to be involved in the immune response and inflammation. People with atopic dermatitis produce high levels of cytokines, which can cause the inflammation of the skin seen in dermatitis. Crisaborole blocks the release of certain cytokines involved in the inflammation process such as tumor necrosis factor alpha, interleukins (IL‑2, IL-4, IL-5), and interferon gamma. By blocking their release, crisaborole is expected to ease the inflammation and therefore relieve symptoms of the disease.

Chemistry

Crisaborole (chemical name: 4- 1-hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)oxyenzonitrile) is a member of the class of benzoxaboroles characterized by the presence of a

boronic acid A boronic acid is an organic compound related to boric acid () in which one of the three hydroxyl groups () is replaced by an alkyl or aryl group (represented by R in the general formula ). As a compound containing a carbon–boron bond, memb ...

hemiester with a phenolic ether and a nitrile. Crisaborole crystallizes into two polymorphs that differ in the conformation of the oxaborole ring. A

cocrystal In materials science (specifically crystallography), cocrystals are "solids that are crystalline, single- phase materials composed of two or more different molecular or ionic compounds generally in a stoichiometric ratio which are neither solva ...

with

4,4'-bipyridine 4,4′-Bipyridine (abbreviated to 4,4′-bipy or 4,4′-bpy) is an organic compound with the formula . It is one of several isomers of bipyridine. It is a colorless solid that is soluble in organic solvents. is mainly used as a precursor to '' ...

has been prepared and studied by

X-ray crystallography X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring th ...

History

Crisaborole was developed by Anacor Pharmaceuticals for the topical treatment of

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ...

. During preclinical and clinical development, crisaborole was called AN2728 and PF-06930164. The drug was assumed to be potential $2bn-a-year blockbuster, when Pfizer acquired Anacor Pharmaceuticals. However, the drug was commercially not successful, reaching only in sales in 2018, and in sales in 2019. Crisaborole was approved for use in the United States in December 2016 and for use in Canada in June 2018. The safety and efficacy of crisaborole were established in two placebo-controlled trials with a total of 1,522 participants ranging in age from two years of age to 79 years of age, with mild to moderate atopic dermatitis. In both trials participants received treatment with either crisaborole or placebo twice daily for 28 days. Neither the participants nor the health care providers knew which treatment was being given until after the trials were completed. Overall, participants receiving crisaborole achieved greater response with clear or almost clear skin after 28 days of treatment. The trials were conducted in the US. Crisaborole, approved for the treatment of mild to moderate atopic dermatitis in the European Union, has been rapidly withdrawn from the European market (March 2020 - February 2022). Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

References

{{Portal bar , Medicine Ethers Nitriles Boronate esters PDE4 inhibitors Drugs developed by Pfizer Phosphodiesterase inhibitors Oxaboroles