Details
Stereochemistry | ACHIRAL |
Molecular Formula | C14H10BNO3 |
Molecular Weight | 251.045 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OB1OCC2=C1C=CC(OC3=CC=C(C=C3)C#N)=C2
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
Molecular Formula | C14H10BNO3 |
Molecular Weight | 251.045 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/?term=19303290Curator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=19303290
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2366459 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=27050693 |
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Target ID: CHEMBL2366442 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=27050693 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | EUCRISA Approved UseEUCRISA is indicated for topical treatment of mild to moderate atopic dermatitis in patients 2 years of age and older. Launch Date2016 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
105 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26777394 |
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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31657024 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
448 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26777394 |
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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31657024 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.17 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26777394 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3% |
CRISABOROLE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse 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) Other AEs:Impetigo (moderate, 1 patient) Application site urticaria (mild|moderate, 2 patients) Dermatitis atopic (severe, 1 patient) Application site irritation (mild, 1 patient) Application site rash (moderate, 1 patient) Sources: Page: p. 120 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=72 Page: 72.0 |
no [IC50 >15 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=72 Page: 72.0 |
no [IC50 >15 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=72 Page: 72.0 |
no [IC50 >15 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=72 Page: 72.0 |
no [IC50 >15 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=72 Page: 72.0 |
no [IC50 >15 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=72 Page: 72.0 |
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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=3 Page: 3.0 |
|||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=4 Page: 4.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=4 Page: 4.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=4 Page: 4.0 |
no | |||
no | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=4 Page: 4.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=4 Page: 4.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=4 Page: 4.0 |
no | |||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=4 Page: 4.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=4 Page: 4.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=4 Page: 4.0 |
no | |||
no | ||||
no | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=89 Page: 89.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=89 Page: 89.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=89 Page: 89.0 |
weak [Inhibition 50 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=89 Page: 89.0 |
weak [Inhibition 50 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=89 Page: 89.0 |
weak [Inhibition 50 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=72 Page: 72.0 |
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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=3 Page: 3.0 |
|||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=89 Page: 89.0 |
yes | |||
yes | ||||
yes | ||||
yes | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=89 Page: 89.0 |
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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=3 Page: 3.0 |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=88 Page: 88.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=88 Page: 88.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=88 Page: 88.0 |
weak | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=88 Page: 88.0 |
weak | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=88 Page: 88.0 |
weak | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=88 Page: 88.0 |
yes | |||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207695Orig1s000ClinPharmR.pdf#page=88 Page: 88.0 |
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
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 |
|
A Phase 2, Randomized, Controlled, Dose-Ranging Study Evaluating Crisaborole Topical Ointment, 0.5% and 2% in Adolescents With Mild to Moderate Atopic Dermatitis. | 2015 Dec |
|
Crisaborole Topical Ointment, 2% in Adults With Atopic Dermatitis: A Phase 2a, Vehicle-Controlled, Proof-of-Concept Study. | 2015 Oct |
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Crisaborole Topical Ointment, 2%: A Nonsteroidal, Topical, Anti-Inflammatory Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic Dermatitis. | 2016 Apr |
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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 |
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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 |
|
Pharmacokinetic Profile, Safety, and Tolerability of Crisaborole Topical Ointment, 2% in Adolescents with Atopic Dermatitis: An Open-Label Phase 2a Study. | 2016 Mar-Apr |
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 Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=27050693
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 20:24:41 GMT 2023
by
admin
on
Fri Dec 15 20:24:41 GMT 2023
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Record UNII |
Q2R47HGR7P
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Record Status |
Validated (UNII)
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N0000182961
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D11AH06
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CHEMBL484785
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Crisaborole
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Q2R47HGR7P
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906673-24-3
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C174863
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Crisaborole
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N0000182960
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CD-176
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
Catalytic domain
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METABOLIC ENZYME -> SUBSTRATE |
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METABOLIC ENZYME -> SUBSTRATE |
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INTERMEDIATE -> INGREDIENT |
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BINDER->LIGAND |
BINDING
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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Related Record | Type | Details | ||
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METABOLITE INACTIVE -> PARENT |
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METABOLITE INACTIVE -> PARENT |
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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