Crisaborole
[CAS# 906673-24-3]

Identification

• Classification: Organic raw materials >> Nitrile compound
• Name: Crisaborole
• Synonyms: AN 2728; 4-[(1,3-Dihydro-1-hydroxy-2,1-benzoxaborol-5-yl)oxy]benzonitrile
• Molecular Formula: C₁₄H₁₀BNO₃
• Molecular Weight: 251.05
• CAS Registry Number: 906673-24-3
• EC Number: 696-120-1
• SMILES: B1(C2=C(CO1)C=C(C=C2)OC3=CC=C(C=C3)C#N)O

Properties

• Solubility: 30 mg/mL (DMSO)
• Density: 1.33±0.1 g/cm³ (20 °C 760 Torr), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2014 ACD/Labs)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319
• Safety Statements: P264-P264+P265-P270-P280-P301+P317-P302+P352-P305+P351+P338-P321-P330-P332+P317-P337+P317-P362+P364-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315

Discovery and Applications

Crisaborole, a novel benzoxaborole compound, was discovered by Anacor Pharmaceuticals during efforts to identify new treatments for inflammatory skin diseases. Developed through structure-based drug design, crisaborole emerged from a series of benzoxaborole derivatives known for their unique ability to inhibit phosphodiesterase 4 (PDE4). The chemical structure of crisaborole features a boron atom that forms a reversible covalent bond with the active site of PDE4, a crucial enzyme in inflammatory pathways. Its synthesis involved optimizing the benzoxaborole scaffold to enhance specificity and efficacy while minimizing potential side effects. Approved by the FDA in 2016, crisaborole represents a significant advancement in dermatological treatments, particularly for atopic dermatitis.

Crisaborole is primarily used as a topical treatment for mild to moderate atopic dermatitis (eczema) in patients two years of age and older. By inhibiting PDE4, crisaborole reduces the production of pro-inflammatory cytokines like TNF-a and IL-4, which are elevated in atopic dermatitis. This reduction in inflammatory signaling alleviates symptoms such as redness, itching, and swelling. Crisaborole's topical formulation allows for targeted application, leading to fewer systemic side effects compared to oral PDE4 inhibitors. Beyond atopic dermatitis, crisaborole's anti-inflammatory properties are being explored for other skin conditions characterized by inflammation and immune dysregulation, such as psoriasis and contact dermatitis. Its ability to modulate inflammatory pathways makes it a candidate for expanding therapeutic options in dermatology.

The inhibition of PDE4 by crisaborole can be beneficial in treating other inflammatory disorders. Research is ongoing to explore its potential in conditions like allergic conjunctivitis, chronic obstructive pulmonary disease (COPD), and inflammatory bowel disease (IBD). Its specific mechanism of action allows for the modulation of immune responses without broadly suppressing the immune system, offering a targeted approach to managing inflammation. Crisaborole's mechanism also helps in reducing pruritus (itch), a common symptom in various inflammatory skin diseases. By decreasing inflammatory mediators that contribute to the sensation of itch, crisaborole provides relief to patients, improving their quality of life.

Crisaborole's topical application minimizes systemic exposure, reducing the risk of side effects commonly associated with systemic PDE4 inhibitors, such as gastrointestinal distress and weight loss. Its safety profile makes it a preferable option, especially for pediatric and elderly populations who may be more susceptible to systemic side effects. As a non-steroidal anti-inflammatory drug (NSAID), crisaborole avoids the side effects associated with long-term steroid use, such as skin thinning and adrenal suppression. This characteristic makes it suitable for long-term management of chronic skin conditions without the concerns linked to steroid therapies.

The development of crisaborole as a topical ointment allows for direct application to affected skin areas, providing localized treatment with minimal systemic absorption. This approach maximizes therapeutic effects where they are needed most and minimizes the risk of systemic side effects.

References

2014. A Review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4-inhibitors in clinical dermatology. Dermatology Online Journal, 20(5).
DOI: 10.5070/d3205022608

2024. Efficacy and safety of crisaborole ointment, 2%, in participants aged ≥45 years with stasis dermatitis: Results from a fully decentralized, randomized, proof-of-concept phase 2a study. Journal of the American Academy of Dermatology, 90(5).
DOI: 10.1016/j.jaad.2023.12.048

2024. Crisaborole-Enthused Glycerosomal Gel for an Augmented Skin Permeation. Recent Advances in Drug Delivery and Formulation, 18(2).
DOI: 10.2174/0126673878283299240418112318