Identification
- Summary
Crisaborole is a non-steroidal topical medication used for the treatment of mild-moderate atopic dermatitis.
- Brand Names
- Eucrisa
- Generic Name
- Crisaborole
- DrugBank Accession Number
- DB05219
- Background
Crisaborole is a novel oxaborole approved by FDA on December 14, 2016 as Eucrisa, a topical treatment of for mild to moderate atopic dermatitis. This non-steroidal agent is efficacious in improving disease severity, reducing the risk of infection and reducing the signs and symptoms in patients 2 years old and older. It reduces the local inflammation in the skin and prevents further exacerbation of the disease with a good safety profile. Its structure contains a boron atom, which facilitates skin penetration and binding to the bimetal center of the phosphodiesterase 4 enzyme. It is currently under development as topical treatment of psoriasis.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Crisaborole (DB05219)
- Weight
- Average: 251.05
Monoisotopic: 251.075373 - Chemical Formula
- C14H10BNO3
- Synonyms
- Crisaborole
- External IDs
- AN-2728
- AN2728
Pharmacology
- Indication
Intended for the topical treatment of mild to moderate atopic dermatitis in patients 2 years of age and older.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Mild atopic dermatitis •••••••••••• Treatment of Moderate atopic dermatitis •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Crisaborole has broad-spectrum anti-inflammatory activity by mainly targeting phosphodiesterase 4 (PDE4) enzyme that is a key regulator of inflammatory cytokine production. As this enzyme is expressed in keratinocytes and immune cells, crisaborole mediates an anti-inflammatory effect on almost all inflammatory cells. Topical application of this drug is useful as it potentiates the localization of this drug in the skin and this anti-inflammatory activity is in the low micromolar range.
- Mechanism of action
Inhibition of PDE4 by crisaborole leads to elevated levels of cyclic adenosine monophosphate (cAMP). Increased intracellular levels of cAMP inhibit the NF-kB pathway and suppress the release of pro-inflammatory mediators such as TNF-alfa and various interleukins that play a causative role in psoriasis and atopic dermatitis. Suppression of downstream effects in different cell types may explain the therapeutic role of crisaborole in immune-mediated skin diseases.
Target Actions Organism UcAMP-specific 3',5'-cyclic phosphodiesterase 4A inhibitorHumans UcAMP-specific 3',5'-cyclic phosphodiesterase 4B inhibitorHumans UcAMP-specific 3',5'-cyclic phosphodiesterase 4C inhibitorHumans UcAMP-specific 3',5'-cyclic phosphodiesterase 4D inhibitorHumans - Absorption
Systemic concentrations of crisaborole were reached by 8 days of twice-daily topical administration. It has low systemic absorption thus poses less risk for developing systemic side effects.
- Volume of distribution
Not Available
- Protein binding
Based on an in vitro study, crisaborole is 97% bound to human plasma proteins
- Metabolism
Crisaborole is substantially metabolized into inactive metabolites. The major metabolite 5-(4-cyanophenoxy)-2-hydroxyl benzylalcohol (metabolite 1), is formed via hydrolysis; this metabolite is further metabolized into downstream metabolites, among which 5-(4-cyanophenoxy)-2-hydroxyl benzoic acid (metabolite 2), formed via oxidation, is also a major metabolite.
- Route of elimination
Renal excretion of metabolites is the major route of elimination.
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Hypersensitivity reactions such as contact urticaria may occur and discontinuation of the treatment is advised. No evidence of mutagenic or clastrogenic potential as well as altered effects on fertility. Oral LD50 value for rats is >500mg/kg.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareDaprodustat The metabolism of Daprodustat can be decreased when combined with Crisaborole. Erdafitinib The serum concentration of Erdafitinib can be increased when it is combined with Crisaborole. Etrasimod The serum concentration of Etrasimod can be increased when it is combined with Crisaborole. Resmetirom The metabolism of Resmetirom can be decreased when combined with Crisaborole. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Eucrisa Ointment 20 mg/1g Topical Pfizer Laboratories Div Pfizer Inc 2017-01-30 Not applicable US 
Eucrisa Ointment 2 % w/w Topical Pfizer Canada Ulc 2018-08-29 Not applicable Canada 
Staquis Ointment 20 mg/g Cutaneous Pfizer Europe Ma Eeig 2020-12-16 2022-02-08 EU 
Staquis Ointment 20 mg/1g Topical Pharmacia & Upjohn Company LLC 2020-11-01 Not applicable US Staquis Ointment 20 mg/g Cutaneous Pfizer Europe Ma Eeig 2020-12-16 2022-02-08 EU
Categories
- ATC Codes
- D11AH06 — Crisaborole
- Drug Categories
- Agents for Dermatitis, Excluding Corticosteroids
- Anti-Inflammatory Agents
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (weak)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (moderate)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (moderate)
- Cytochrome P-450 Enzyme Inhibitors
- Dermatologicals
- Phosphodiesterase 4 Inhibitors
- Phosphodiesterase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Ethers
- Direct Parent
- Diarylethers
- Alternative Parents
- Phenoxy compounds / Phenol ethers / Benzonitriles / Oxaborole derivatives / Boronic acid esters / Oxacyclic compounds / Organic metalloid salts / Nitriles / Organometalloid compounds / Hydrocarbon derivatives
- Substituents
- 1,2-oxaborole derivative / Aromatic heteropolycyclic compound / Benzenoid / Benzonitrile / Boronic acid derivative / Boronic acid ester / Carbonitrile / Cyanide / Diaryl ether / Hydrocarbon derivative
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Q2R47HGR7P
- CAS number
- 906673-24-3
- InChI Key
- USZAGAREISWJDP-UHFFFAOYSA-N
- InChI
- 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
- IUPAC Name
- 4-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)oxy]benzonitrile
- SMILES
- OB1OCC2=C1C=CC(OC1=CC=C(C=C1)C#N)=C2
References
- General References
- Paller AS, Tom WL, Lebwohl MG, Blumenthal RL, Boguniewicz M, Call RS, Eichenfield LF, Forsha DW, Rees WC, Simpson EL, Spellman MC, Stein Gold LF, Zaenglein AL, Hughes MH, Zane LT, Hebert AA: Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016 Sep;75(3):494-503.e4. doi: 10.1016/j.jaad.2016.05.046. Epub 2016 Jul 11. [Article]
- Paton DM: Crisaborole: Phosphodiesterase inhibitor for treatment of atopic dermatitis. Drugs Today (Barc). 2017 Apr;53(4):239-245. doi: 10.1358/dot.2017.53.4.2604174. [Article]
- Zane LT, Hughes MH, Shakib S: Tolerability of Crisaborole Ointment for Application on Sensitive Skin Areas: A Randomized, Double-Blind, Vehicle-Controlled Study in Healthy Volunteers. Am J Clin Dermatol. 2016 Oct;17(5):519-526. [Article]
- Moustafa F, Feldman SR: A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4-inhibitors in clinical dermatology. Dermatol Online J. 2014 May 16;20(5):22608. [Article]
- External Links
- KEGG Drug
- D10873
- PubChem Compound
- 44591583
- PubChem Substance
- 175426957
- ChemSpider
- 24701949
- BindingDB
- 50277665
- 1865953
- ChEBI
- 134677
- ChEMBL
- CHEMBL484785
- ZINC
- ZINC000169748244
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Crisaborole
- FDA label
- Download (185 KB)
- MSDS
- Download (42.3 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Atopic Dermatitis 2 4 Completed Other Atopic Dermatitis 1 4 Completed Treatment Atopic Dermatitis 2 4 Completed Treatment Seborrheic Dermatitis 1 4 Terminated Treatment Atopic Dermatitis 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Ointment Topical 2 % w/w Ointment Topical 20 mg/1g Ointment Cutaneous 2.0000 g Ointment Cutaneous 20 MG/G - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8039451 Yes 2011-10-18 2026-12-11 US US8501712 Yes 2013-08-06 2027-08-16 US US8168614 Yes 2012-05-01 2030-07-20 US US9682092 Yes 2017-06-20 2027-08-16 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Insoluble FDA Label - Predicted Properties
Property Value Source Water Solubility 0.0234 mg/mL ALOGPS logP 2.6 ALOGPS logP 3.34 Chemaxon logS -4 ALOGPS pKa (Strongest Acidic) 8.95 Chemaxon pKa (Strongest Basic) -3.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 62.48 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 65.6 m3·mol-1 Chemaxon Polarizability 25.9 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9563 Blood Brain Barrier + 0.9383 Caco-2 permeable - 0.5845 P-glycoprotein substrate Non-substrate 0.547 P-glycoprotein inhibitor I Non-inhibitor 0.8845 P-glycoprotein inhibitor II Non-inhibitor 0.8936 Renal organic cation transporter Non-inhibitor 0.6515 CYP450 2C9 substrate Non-substrate 0.7986 CYP450 2D6 substrate Non-substrate 0.7423 CYP450 3A4 substrate Non-substrate 0.6599 CYP450 1A2 substrate Inhibitor 0.5611 CYP450 2C9 inhibitor Non-inhibitor 0.6637 CYP450 2D6 inhibitor Non-inhibitor 0.706 CYP450 2C19 inhibitor Non-inhibitor 0.5344 CYP450 3A4 inhibitor Non-inhibitor 0.8253 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.771 Ames test AMES toxic 0.5445 Carcinogenicity Non-carcinogens 0.8567 Biodegradation Not ready biodegradable 0.9645 Rat acute toxicity 2.4979 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7405 hERG inhibition (predictor II) Inhibitor 0.5739
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Metal ion binding
- Specific Function
- Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
- Gene Name
- PDE4A
- Uniprot ID
- P27815
- Uniprot Name
- cAMP-specific 3',5'-cyclic phosphodiesterase 4A
- Molecular Weight
- 98142.155 Da
References
- Freund YR, Akama T, Alley MR, Antunes J, Dong C, Jarnagin K, Kimura R, Nieman JA, Maples KR, Plattner JJ, Rock F, Sharma R, Singh R, Sanders V, Zhou Y: Boron-based phosphodiesterase inhibitors show novel binding of boron to PDE4 bimetal center. FEBS Lett. 2012 Sep 21;586(19):3410-4. doi: 10.1016/j.febslet.2012.07.058. Epub 2012 Jul 25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Metal ion binding
- Specific Function
- Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging f...
- Gene Name
- PDE4B
- Uniprot ID
- Q07343
- Uniprot Name
- cAMP-specific 3',5'-cyclic phosphodiesterase 4B
- Molecular Weight
- 83342.695 Da
References
- Freund YR, Akama T, Alley MR, Antunes J, Dong C, Jarnagin K, Kimura R, Nieman JA, Maples KR, Plattner JJ, Rock F, Sharma R, Singh R, Sanders V, Zhou Y: Boron-based phosphodiesterase inhibitors show novel binding of boron to PDE4 bimetal center. FEBS Lett. 2012 Sep 21;586(19):3410-4. doi: 10.1016/j.febslet.2012.07.058. Epub 2012 Jul 25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Metal ion binding
- Specific Function
- Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
- Gene Name
- PDE4C
- Uniprot ID
- Q08493
- Uniprot Name
- cAMP-specific 3',5'-cyclic phosphodiesterase 4C
- Molecular Weight
- 79900.795 Da
References
- Freund YR, Akama T, Alley MR, Antunes J, Dong C, Jarnagin K, Kimura R, Nieman JA, Maples KR, Plattner JJ, Rock F, Sharma R, Singh R, Sanders V, Zhou Y: Boron-based phosphodiesterase inhibitors show novel binding of boron to PDE4 bimetal center. FEBS Lett. 2012 Sep 21;586(19):3410-4. doi: 10.1016/j.febslet.2012.07.058. Epub 2012 Jul 25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
- Gene Name
- PDE4D
- Uniprot ID
- Q08499
- Uniprot Name
- cAMP-specific 3',5'-cyclic phosphodiesterase 4D
- Molecular Weight
- 91114.1 Da
References
- Freund YR, Akama T, Alley MR, Antunes J, Dong C, Jarnagin K, Kimura R, Nieman JA, Maples KR, Plattner JJ, Rock F, Sharma R, Singh R, Sanders V, Zhou Y: Boron-based phosphodiesterase inhibitors show novel binding of boron to PDE4 bimetal center. FEBS Lett. 2012 Sep 21;586(19):3410-4. doi: 10.1016/j.febslet.2012.07.058. Epub 2012 Jul 25. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
Drug created at October 21, 2007 22:24 / Updated at November 02, 2022 09:01