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Details

Stereochemistry ACHIRAL
Molecular Formula C14H10BNO3
Molecular Weight 251.0457
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CRISABOROLE

SMILES

c1cc(ccc1C#N)Oc2ccc3c(c2)COB3O

InChI

InChIKey=USZAGAREISWJDP-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created using several sources including:| https://www.ncbi.nlm.nih.gov/pubmed/27335049 | https://www.ncbi.nlm.nih.gov/pubmed/27525671 | https://www.ncbi.nlm.nih.gov/pubmed/27417017 | https://www.ncbi.nlm.nih.gov/pubmed/?term=27050693

Crisaborole is a topically administered, boron-containing, anti-inflammatory compound that inhibits the phosphodiesterase-4 (PDE4) activity and thereby suppresses the cytokine release of TNFalpha, IL-12, IL-23 and other cytokines. PDE4 is an an enzyme that converts the intracellular second messenger 3'5'-cyclic adenosine monophosphate (cAMP) into the active metabolite adenosine monophosphate (AMP). By inhibiting PDE4 and thus increasing levels of cAMP, crisaborole controls inflammation. The use of boron chemistry enabled synthesis of a low-molecular-weight compound (251 daltons), thereby facilitating effective penetration of crisaborole through human skin. Crisaborole is in clinical development for the topical treatment of psoriasis and being pursued for the topical treatment of atopic dermatitis. Preliminary studies in children and adults demonstrated favorable efficacy and safety profiles. Crisaborole may represent an anti-inflammatory option that safely minimizes the symptoms and severity of AD and that can be used for both acute and long-term management.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
EUCRISA

Approved Use

EUCRISA is indicated for topical treatment of mild to moderate atopic dermatitis in patients 2 years of age and older.

Launch Date

1.48167354E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
105 ng/mL
30000 mg/m² single, topical
dose: 30000 mg/m²
route of administration: Topical
experiment type: SINGLE
co-administered:
CRISABOROLE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: UNKNOWN
163.7 ng/mL
435 mg single, topical
dose: 435 mg
route of administration: Topical
experiment type: SINGLE
co-administered:
CRISABOROLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
448 ng × h/mL
30000 mg/m² single, topical
dose: 30000 mg/m²
route of administration: Topical
experiment type: SINGLE
co-administered:
CRISABOROLE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: UNKNOWN
1171 ng × h/mL
435 mg single, topical
dose: 435 mg
route of administration: Topical
experiment type: SINGLE
co-administered:
CRISABOROLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.17 h
30000 mg/m² single, topical
dose: 30000 mg/m²
route of administration: Topical
experiment type: SINGLE
co-administered:
CRISABOROLE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
3%
CRISABOROLE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
2 % 2 times / day steady, topical
Recommended
Dose: 2 %, 2 times / day
Route: topical
Route: steady
Dose: 2 %, 2 times / day
Sources: Page: p. 120
unhealthy, 2-21 years
n = 1021
Health Status: unhealthy
Age Group: 2-21 years
Sex: M+F
Population Size: 1021
Sources: Page: p. 120
Disc. AE: Application site pain, Impetigo...
Other AEs: Application site rash...
AEs leading to
discontinuation/dose reduction:
Application site pain (moderate|severe, 3 patients)
Impetigo (moderate, 1 patient)
Application site urticaria (mild|moderate, 2 patients)
Dermatitis atopic (severe, 1 patient)
Application site irritation (mild, 1 patient)
Other AEs:
Application site rash (moderate, 1 patient)
Sources: Page: p. 120
AEs

AEs

AESignificanceDosePopulation
Application site irritation mild, 1 patient
Disc. AE
2 % 2 times / day steady, topical
Recommended
Dose: 2 %, 2 times / day
Route: topical
Route: steady
Dose: 2 %, 2 times / day
Sources: Page: p. 120
unhealthy, 2-21 years
n = 1021
Health Status: unhealthy
Age Group: 2-21 years
Sex: M+F
Population Size: 1021
Sources: Page: p. 120
Application site urticaria mild|moderate, 2 patients
Disc. AE
2 % 2 times / day steady, topical
Recommended
Dose: 2 %, 2 times / day
Route: topical
Route: steady
Dose: 2 %, 2 times / day
Sources: Page: p. 120
unhealthy, 2-21 years
n = 1021
Health Status: unhealthy
Age Group: 2-21 years
Sex: M+F
Population Size: 1021
Sources: Page: p. 120
Application site rash moderate, 1 patient
2 % 2 times / day steady, topical
Recommended
Dose: 2 %, 2 times / day
Route: topical
Route: steady
Dose: 2 %, 2 times / day
Sources: Page: p. 120
unhealthy, 2-21 years
n = 1021
Health Status: unhealthy
Age Group: 2-21 years
Sex: M+F
Population Size: 1021
Sources: Page: p. 120
Impetigo moderate, 1 patient
Disc. AE
2 % 2 times / day steady, topical
Recommended
Dose: 2 %, 2 times / day
Route: topical
Route: steady
Dose: 2 %, 2 times / day
Sources: Page: p. 120
unhealthy, 2-21 years
n = 1021
Health Status: unhealthy
Age Group: 2-21 years
Sex: M+F
Population Size: 1021
Sources: Page: p. 120
Application site pain moderate|severe, 3 patients
Disc. AE
2 % 2 times / day steady, topical
Recommended
Dose: 2 %, 2 times / day
Route: topical
Route: steady
Dose: 2 %, 2 times / day
Sources: Page: p. 120
unhealthy, 2-21 years
n = 1021
Health Status: unhealthy
Age Group: 2-21 years
Sex: M+F
Population Size: 1021
Sources: Page: p. 120
Dermatitis atopic severe, 1 patient
Disc. AE
2 % 2 times / day steady, topical
Recommended
Dose: 2 %, 2 times / day
Route: topical
Route: steady
Dose: 2 %, 2 times / day
Sources: Page: p. 120
unhealthy, 2-21 years
n = 1021
Health Status: unhealthy
Age Group: 2-21 years
Sex: M+F
Population Size: 1021
Sources: Page: p. 120
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >15 uM]
no [IC50 >15 uM]
no [IC50 >15 uM]
no [IC50 >15 uM]
no [IC50 >15 uM]
no [IC50 >15 uM]
no [Ki 8.96 uM]
no (co-administration study)
Comment: The most sensitive enzyme, CYP2C9, was further investigated for drug interaction potential in a clinical trial (AN2728-PK-101) using 25 mg oral dose of warfarin as a CYP2C9 substrate. The results of this clinical trial showed there was no drug interaction potential.
Page: 3.0
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak [Inhibition 50 uM]
weak [Inhibition 50 uM]
weak [Inhibition 50 uM]
yes [IC50 25.3 uM]
yes [Ki 22.3 uM]
no (co-administration study)
Comment: To address the potential for crisaborole to inhibit CYP2C19 following clinical application of Crisaborole Ointment, 2%, the exposure of crisaborole, as determined in the maximal use PK trial (AN2728-AD-102) conducted in pediatric subjects with AD, was considered for the calculation of I/Ki. In this study, after topical administration of Crisaborole Ointment, 2% at a dose of 3 mg/cm2 applied to treatable BSA (mean %BSA = 48.7%), the mean ±SD plasma Cmax on Day 8 was 0.506 ± 0.781 μM (127± 196 ng/mL). Hence the ratios of [I]/ Ki for competitive inhibition (0.506/8.96 or 0.056) and metabolismbased inhibition (0.506/22.3 or 0.023) would be <0.1 and the corresponding R values would be < 1.1 which indicates that the probability of crisaborole to inhibit CYP2C19 under conditions of clinical use is low.
Page: 3.0
yes
yes
yes
yes
yes
yes
no (co-administration study)
Comment: The most sensitive enzyme, CYP2C9, was further investigated for drug interaction potential in a clinical trial (AN2728-PK-101) using 25 mg oral dose of warfarin as a CYP2C9 substrate. The results of this clinical trial showed there was no drug interaction potential.
Page: 3.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
weak
weak
weak
yes
yes
yes
yes
yes
yes
yes
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis.
2009 Apr 15
Crisaborole Topical Ointment, 2% in Adults With Atopic Dermatitis: A Phase 2a, Vehicle-Controlled, Proof-of-Concept Study.
2015 Oct
Crisaborole Topical Ointment, 2%: A Nonsteroidal, Topical, Anti-Inflammatory Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic Dermatitis.
2016 Apr
Post Hoc Analyses of the Effect of Crisaborole Topical Ointment, 2% on Atopic Dermatitis: Associated Pruritus from Phase 1 and 2 Clinical Studies.
2016 Feb
Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open-Label, Maximal-Use Systemic Exposure Study.
2016 Jul
Treatment of Skin Inflammation with Benzoxaborole Phosphodiesterase Inhibitors: Selectivity, Cellular Activity, and Effect on Cytokines Associated with Skin Inflammation and Skin Architecture Changes.
2016 Sep
Patents

Sample Use Guides

2% AN2728 applied twice daily for up to 28 days in children, adolescents, and adults (ages 2 years and older) with atopic dermatitis
Route of Administration: Topical
In vitro experiments showed that crisaborole inhibits cytokine production from peripheral blood mononuclear cells in a pattern similar to other PDE4 inhibitors and distinct from corticosteroids.
Name Type Language
CRISABOROLE
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
AN-2728
Code English
EUCRISA
Brand Name English
BENZONITRILE, 4-((1,3-DIHYDRO-1-HYDROXY-2,1-BENZOXABOROL-5-YL)OXY)-
Systematic Name English
CRISABOROLE [MI]
Common Name English
CRISABOROLE [INN]
Common Name English
CRISABOROLE [ORANGE BOOK]
Common Name English
AN2728
Code English
4-((1-HYDROXY-1,3-DIHYDROBENZO(C)(1,2)OXABOROL-6-YL)OXY)BENZONITRILE
Systematic Name English
CRISABOROLE [USAN]
Common Name English
CRISABOROLE [WHO-DD]
Common Name English
Classification Tree Code System Code
NDF-RT N0000182961
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
WHO-ATC D11AH06
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL484785
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY
LACTMED
Crisaborole
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY
RXCUI
1865953
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY
DRUG BANK
DB05219
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY
CAS
906673-24-3
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY
NCI_THESAURUS
C174863
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY
PUBCHEM
44591583
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY
MERCK INDEX
M11973
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY
DRUG CENTRAL
5201
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY
WIKIPEDIA
Crisaborole
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY
NDF-RT
N0000182960
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY Phosphodiesterase 4 Inhibitors [MoA]
INN
10024
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY
EPA CompTox
906673-24-3
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY
FDA UNII
Q2R47HGR7P
Created by admin on Sat Jun 26 02:09:12 UTC 2021 , Edited by admin on Sat Jun 26 02:09:12 UTC 2021
PRIMARY