Biology:Crisaborole

From HandWiki
Short description: Chemical compound
Crisaborole
Crisaborole.svg
Clinical data
Pronunciation/juːˈkrɪsə/ yoo-KRIS-ə
Trade namesEucrisa, Staquis
Other namesAN-2728
AHFS/Drugs.comMonograph
MedlinePlusa617019
License data
Pregnancy
category
  • AU: B1
  • US: N (Not classified yet)
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  • EU: authorization withdrawn on request of pharmaceutical company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
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC14H10BNO3
Molar mass251.05 g·mol−1
3D model (JSmol)

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]

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

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

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.[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

Pharmacodynamics

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

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

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

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "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. ↑ 2.0 2.1 2.2 "Eucrisa- crisaborole ointment". 21 April 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=609b77de-1ca3-4783-b8f5-01a9c0f1d77d. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "Staquis EPAR". 29 January 2020. https://www.ema.europa.eu/en/medicines/human/EPAR/staquis.  Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  4. ↑ "Topical Administration of Crisaborole in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta-Analysis" (in en). Dermatologic Therapy 2023: 1–9. 2023-02-06. doi:10.1155/2023/1869934. ISSN 1529-8019. 
  5. ↑ "PRODUCT MONOGRAPH". 2018-06-07. https://pdf.hres.ca/dpd_pm/00045835.PDF. 
  6. ↑ 6.0 6.1 6.2 6.3 "A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4-inhibitors in clinical dermatology". Dermatology Online Journal 20 (5): 22608. May 2014. doi:10.5070/D3205022608. PMID 24852768. http://escholarship.org/uc/item/2hx1m6kv.pdf. 
  7. ↑ "WHO Drug Information, Vol. 29, No. 3, 2015. International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 74". World Health Information. p. 391. https://www.who.int/medicines/publications/druginformation/innlists/RL74.pdf. 
  8. ↑ "Exploration of Solid Forms of Crisaborole: Crystal Engineering Identifies Polymorphism in Commercial Sources and Facilitates Cocrystal Formation". Crystal Growth & Design 18 (8): 4416–4419. 2018. doi:10.1021/acs.cgd.8b00375. ISSN 1528-7483. 
  9. ↑ "AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis". Current Opinion in Investigational Drugs 10 (11): 1236–42. November 2009. PMID 19876791. 
  10. ↑ "Neue Wirkstoffe: Crisaborol" (in German). Österreichische Apotheker-Zeitung (17/2016). 16 August 2016. 
  11. ↑ "Crisaborole". AdisInsight. http://adisinsight.springer.com/drugs/800024239. 
  12. ↑ "Pfizer to Acquire Anacor". Pfizer (Press release). 16 May 2016. Retrieved 28 April 2020.
  13. ↑ "Pfizer Financial Report". Pfizer. https://s21.q4cdn.com/317678438/files/doc_financials/Quarterly/2019/q4/Q4-2019-PFE-Earnings-Release.pdf. 
  14. ↑ "Eucrisa (crisaborole) Ointment". 23 January 2017. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000TOC.cfm. 
  15. ↑ "Eucrisa Regulatory Decision Summary". 2014-10-23. https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00420. 
  16. ↑ 16.0 16.1 16.2 16.3 "Drug Trials Snapshot: Eucrisa". 14 December 2016. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-eucrisa.  This article incorporates text from this source, which is in the public domain.

External links



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Crisaborole&oldid=3640789"