Wikipedia

Crisaborole

(Redirected from AN2728)

Crisaborole, sold under the brand name Eucrisa among others, is a nonsteroidal topical medication used for the treatment of mild-to-moderate atopic dermatitis (eczema) in adults and children.[1][2][3][4]

Crisaborole
Clinical data
Pronunciation/juːˈkrɪsə/ yoo-KRIS-ə
Trade namesEucrisa, Staquis
Other namesAN-2728
AHFS/Drugs.comMonograph
MedlinePlusa617019
License data
Pregnancy
category
  • AU: B1
Routes of
administration		Topical (ointment)
ATC code
Legal status
Legal status
  • CA: ℞-only
  • US: ℞-only
  • EU: authorization withdrawn on request of pharmaceutical company
  • In general: ℞ (Prescription only)
Identifiers
  • 4-[(1-Hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)oxy]benzonitrile
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.225.309 Edit this at Wikidata
Chemical and physical data
FormulaC14H10BNO3
Molar mass251.05 g·mol−1
3D model (JSmol)
  • B1(c2ccc(cc2CO1)Oc3ccc(cc3)C#N)O
  • InChI=1S/C14H10BNO3/c16-8-10-1-3-12(4-2-10)19-13-5-6-14-11(7-13)9-18-15(14)17/h1-7,17H,9H2
  • Key:USZAGAREISWJDP-UHFFFAOYSA-N

The most common side effects are reactions at the application site (including burning or stinging).[3]

Crisaborole is a phosphodiesterase 4 (PDE-4) inhibitor, although its specific mechanism of action in atopic dermatitis is not known.[1][2]

Side effects edit

At the site of application, crisaborole may cause burning or stinging. Rarely, there may be an allergic reaction.[5]

Medical uses edit

In the US, crisaborole is indicated for topical treatment of mild to moderate atopic dermatitis in people three months of age and older.[2]

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.[3]

Pharmacology edit

Pharmacodynamics edit

Crisaborole is a phosphodiesterase-4 inhibitor, mainly acting on phosphodiesterase 4B (PDE4B), which causes inflammation.[6] Chemically, crisaborole is a phenoxybenzoxaborole.[6] Inhibition of PDE4B appears to suppress the release of tumor necrosis factor alpha (TNFα), interleukin-12 (IL-12), IL-23 and other cytokines, proteins believed to be involved in the immune response and inflammation.[6]

People with atopic dermatitis produce high levels of proteins called cytokines, which can cause the inflammation of the skin seen in dermatitis.[3] 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.[3] By blocking their release, crisaborole is expected to ease the inflammation and therefore relieve symptoms of the disease.[3]

Chemistry edit

Crisaborole (chemical name: 4-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)oxy]benzonitrile) is a member of the class of benzoxaboroles characterized by the presence of a boronic acid hemiester with a phenolic ether and a nitrile.[7] Crisaborole crystallizes into two polymorphs that differ in the conformation of the oxaborole ring. A cocrystal with 4,4'-bipyridine has been prepared and studied by X-ray crystallography.[8]

History edit

Crisaborole was developed by Anacor Pharmaceuticals for the topical treatment of psoriasis.[9][6][10] During preclinical and clinical development, crisaborole was called AN2728 and PF-06930164.[11] The drug was assumed to be potential $2bn-a-year blockbuster, when Pfizer acquired Anacor Pharmaceuticals.[12] However, the drug was commercially not successful, reaching only US$147 million in sales in 2018, and US$138 million in sales in 2019.[13]

Crisaborole was approved for use in the United States in December 2016[14][1] and for use in Canada in June 2018.[15]

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.[1] In both trials participants received treatment with either crisaborole or placebo twice daily for 28 days.[16] Neither the participants nor the health care providers knew which treatment was being given until after the trials were completed.[16] Overall, participants receiving crisaborole achieved greater response with clear or almost clear skin after 28 days of treatment.[1][16] The trials were conducted in the US.[16]

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).[3]

See also edit

References edit

  1. ^ a b c d e "FDA Approves Eucrisa for Eczema" (Press release). U.S. Food and Drug Administration (FDA). 14 December 2016.   This article incorporates text from this source, which is in the public domain.
  2. ^ a b c "Eucrisa- crisaborole ointment". DailyMed. 21 April 2020. Retrieved 28 April 2020.
  3. ^ a b c d e f g "Staquis EPAR". European Medicines Agency (EMA). 29 January 2020. Retrieved 28 April 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  4. ^ He Y, Liu J, Wang Y, Kuai W, Liu R, Wu J (6 February 2023). Pimpinelli N (ed.). "Topical Administration of Crisaborole in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta-Analysis". Dermatologic Therapy. 2023: 1–9. doi:10.1155/2023/1869934. ISSN 1529-8019.
  5. ^ "PRODUCT MONOGRAPH" (PDF). Government of Canada. 7 June 2018. Archived (PDF) from the original on 7 April 2019. Retrieved 7 April 2019.
  6. ^ a b c d Moustafa F, Feldman SR (May 2014). "A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4-inhibitors in clinical dermatology" (PDF). Dermatology Online Journal. 20 (5): 22608. doi:10.5070/D3205022608. PMID 24852768.
  7. ^ "WHO Drug Information, Vol. 29, No. 3, 2015. International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 74" (PDF). World Health Information. p. 391. Retrieved 26 April 2016.
  8. ^ Campillo-Alvarado G, Didden TD, Oburn SM, Swenson DC, MacGillivray LR (2018). "Exploration of Solid Forms of Crisaborole: Crystal Engineering Identifies Polymorphism in Commercial Sources and Facilitates Cocrystal Formation". Crystal Growth & Design. 18 (8): 4416–4419. doi:10.1021/acs.cgd.8b00375. ISSN 1528-7483.
  9. ^ Nazarian R, Weinberg JM (November 2009). "AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis". Current Opinion in Investigational Drugs. 10 (11): 1236–42. PMID 19876791.
  10. ^ Spreitzer H (16 August 2016). "Neue Wirkstoffe: Crisaborol". Österreichische Apotheker-Zeitung (in German) (17/2016).
  11. ^ "Crisaborole". AdisInsight. Retrieved 24 July 2017.
  12. ^ "Pfizer to Acquire Anacor". Pfizer (Press release). 16 May 2016. Retrieved 28 April 2020.
  13. ^ "Pfizer Financial Report" (PDF). Pfizer. Retrieved 9 April 2020.
  14. ^ "Eucrisa (crisaborole) Ointment". U.S. Food and Drug Administration (FDA). 23 January 2017. Retrieved 28 April 2020.
  15. ^ "Eucrisa Regulatory Decision Summary". Health Canada. 23 October 2014. Archived from the original on 14 September 2019. Retrieved 14 September 2019.
  16. ^ a b c d "Drug Trials Snapshot: Eucrisa". U.S. Food and Drug Administration (FDA). 14 December 2016. Retrieved 28 April 2020.   This article incorporates text from this source, which is in the public domain.

External links edit

  • "Crisaborole". Drug Information Portal. U.S. National Library of Medicine.
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