crisaborole 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
5201 906673-24-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • staquis
  • crisaborole
  • AN2728
  • eucrisa
Crisaborole is a phosphodiesterase 4 (PDE-4) inhibitor. PDE-4 inhibition results in increased intracellular cyclic adenosine monophosphate (cAMP) levels. The specific mechanism(s) by which crisaborole exerts its therapeutic action for the treatment of atopic dermatitis is not well defined.
  • Molecular weight: 251.05
  • Formula: C14H10BNO3
  • CLOGP: 2.63
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 1
  • TPSA: 62.48
  • ALOGS: -4.03
  • ROTB: 2
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
S (Water solubility) 0.11 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.906 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.773 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 50.003 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 201.837 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 1.590 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 4.520 % High 1
herg hERG pIC50 4.825 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 63.826 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 27.990 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 1.570 % High 1
kinase-safety-class ACVR2B,AURKA,AXL,BTK,CAMK2D,CDK5,CDK9,DDR1,EIF2AK3,ERBB2,GRK2,ITK,MAP2K6,MAPK7,MAPKAPK2,PDK1,PDK2,PDK4,PIK3CB,PIK3CG,PRKDC,STK33,TEK,TTK 24
kinase-selectivity-class MAP2K6 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.045 High 1
mh-clint Mouse hepatocyte intrinsic clearance 174.582 High 1
mppb Mouse plasma protein binding (% unbound) 2.720 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 0.439 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 4.780 % High 1
rh-clint Rat hepatocyte intrinsic clearance 94.406 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 38.090 % High 1
rppb Rat plasma protein binding (% unbound) 1.780 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 61.518 uM High 1

Approvals:

DateAgencyCompanyOrphan
March 27, 2020 EMA Pfizer Europe MA EEIG
Dec. 14, 2016 FDA ANACOR PHARMS INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Application site pain 2030.95 37.10 334 5233 4386 90618494
Burning sensation 687.71 37.10 223 5344 63229 90559651
Dermatitis atopic 494.60 37.10 138 5429 23334 90599546
Drug ineffective 393.79 37.10 448 5119 1383850 89239030
Eczema 246.82 37.10 100 5467 52770 90570110
Application site erythema 244.23 37.10 58 5509 5150 90617730
Skin burning sensation 187.84 37.10 63 5504 19548 90603332
Eyelid irritation 174.35 37.10 33 5534 975 90621905
Pruritus 152.34 37.10 176 5391 541349 90081531
Condition aggravated 126.26 37.10 168 5399 595377 90027503
Dry skin 122.78 37.10 73 5494 88000 90534880
Application site pruritus 122.25 37.10 32 5535 4215 90618665
Drug ineffective for unapproved indication 119.15 37.10 65 5502 66579 90556301
Off label use 110.30 37.10 221 5346 1102031 89520849
Rash 107.70 37.10 182 5385 795918 89826962
Application site swelling 104.50 37.10 20 5547 627 90622253
Erythema 101.03 37.10 95 5472 229151 90393729
Drug effective for unapproved indication 98.37 37.10 31 5536 7887 90614993
Skin irritation 85.57 37.10 32 5535 13571 90609309
Eye irritation 80.34 37.10 40 5527 33938 90588942
Skin exfoliation 68.74 37.10 46 5521 67867 90555013
Sleep disorder due to a general medical condition 67.32 37.10 39 5528 44699 90578181
Dermatitis 67.25 37.10 31 5536 22189 90600691
Application site burn 62.45 37.10 14 5553 960 90621920
Product use in unapproved indication 54.86 37.10 84 5483 336152 90286728
Application site irritation 47.99 37.10 13 5554 1948 90620932
Therapeutic product effect incomplete 47.52 37.10 59 5508 193837 90429043
Application site discolouration 46.84 37.10 11 5556 927 90621953
Application site exfoliation 43.37 37.10 9 5558 428 90622452
Therapeutic product ineffective 40.88 37.10 12 5555 2402 90620478
Skin disorder 39.88 37.10 26 5541 36680 90586200
Skin fissures 39.09 37.10 21 5546 20788 90602092
Application site inflammation 38.64 37.10 8 5559 376 90622504
Application site dryness 38.29 37.10 7 5560 170 90622710
Therapeutic response shortened 37.23 37.10 21 5546 22858 90600022

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Application site pain 1081.65 98.71 175 2352 2154 42616654
Burning sensation 391.02 98.71 111 2416 20902 42597906
Dermatitis atopic 335.31 98.71 88 2439 12316 42606492
Drug ineffective 296.10 98.71 262 2265 629935 41988873
Application site erythema 155.74 98.71 35 2492 2531 42616277
Pruritus 140.76 98.71 104 2423 188667 42430141
Rash 105.94 98.71 104 2423 276850 42341958

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Application site pain 1982.38 47.39 332 6108 5167 110577692
Drug ineffective 681.86 47.39 612 5828 1519928 109062931
Burning sensation 611.64 47.39 206 6234 69006 110513853
Dermatitis atopic 536 47.39 148 6292 25393 110557466
Application site erythema 322.61 47.39 73 6367 5537 110577322
Eczema 260.60 47.39 112 6328 72181 110510678
Pruritus 237.83 47.39 225 6215 581335 110001524
Condition aggravated 198.94 47.39 228 6212 734608 109848251
Skin burning sensation 184.48 47.39 63 6377 21762 110561097
Off label use 184.46 47.39 318 6122 1499867 109082992
Rash 173.79 47.39 225 6215 820739 109762120
Drug ineffective for unapproved indication 171.42 47.39 94 6346 102744 110480115
Dry skin 170.12 47.39 95 6345 107558 110475301
Application site pruritus 154.46 47.39 38 6402 4122 110578737
Erythema 146.52 47.39 127 6313 291320 110291539
Eyelid irritation 141.59 47.39 28 6412 1103 110581756
Skin irritation 95.89 47.39 36 6404 16283 110566576
Therapeutic product effect incomplete 95.47 47.39 89 6351 223716 110359143
Eye irritation 89.05 47.39 42 6398 33410 110549449
Application site swelling 87.44 47.39 18 6422 869 110581990
Dermatitis 86.77 47.39 39 6401 27798 110555061
Treatment failure 86.45 47.39 93 6347 277141 110305718
Skin exfoliation 81.05 47.39 55 6385 87596 110495263
Sleep disorder due to a general medical condition 76.83 47.39 44 6396 52068 110530791
Application site irritation 73.44 47.39 18 6422 1919 110580940
Application site discolouration 67.63 47.39 15 6425 1034 110581825
Skin disorder 62.62 47.39 36 6404 42877 110539982
Application site burn 62.59 47.39 14 6426 1003 110581856
Skin fissures 59.88 47.39 29 6411 24429 110558430
Application site vesicles 51.60 47.39 13 6427 1551 110581308
Product use in unapproved indication 49.20 47.39 91 6349 447286 110135573
Discomfort 48.37 47.39 61 6379 214646 110368213
Application site dryness 47.84 47.39 9 6431 271 110582588

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC D11AH06 DERMATOLOGICALS
OTHER DERMATOLOGICAL PREPARATIONS
OTHER DERMATOLOGICAL PREPARATIONS
Agents for dermatitis, excluding corticosteroids
FDA MoA N0000182960 Phosphodiesterase 4 Inhibitors
FDA EPC N0000182961 Phosphodiesterase 4 Inhibitor
CHEBI has role CHEBI:35475 non-steroidal anti-inflammatory drug
CHEBI has role CHEBI:50177 dermatologic drug
CHEBI has role CHEBI:50748 antipsoriatic
CHEBI has role CHEBI:68844 phosphodiesterase IV inhibitor

Related Drugs by ATC class:

D11AH Agents for dermatitis, excluding corticosteroids 11 drugs
abrocitinibalitretinoincromoglicic aciddelgocitinibdupilumablebrikizumabnemolizumabpimecrolimusruxolitinibtacrolimustralokinumab

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Atopic dermatitis indication 24079001 DOID:3310




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 7.8 acidic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
2% EUCRISA ANACOR PHARMS INC N207695 Dec. 14, 2016 RX OINTMENT TOPICAL 8501712 Feb. 16, 2027 METHOD OF TREATING MILD TO MODERATE ATOPIC DERMATITIS.
2% EUCRISA ANACOR PHARMS INC N207695 Dec. 14, 2016 RX OINTMENT TOPICAL 9682092 Feb. 16, 2027 METHOD OF TREATING MILD TO MODERATE ATOPIC DERMATITIS.
2% EUCRISA ANACOR PHARMS INC N207695 Dec. 14, 2016 RX OINTMENT TOPICAL 8168614 Jan. 20, 2030 METHOD OF TREATING MILD TO MODERATE ATOPIC DERMATITIS.

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
2% EUCRISA ANACOR PHARMS INC N207695 Dec. 14, 2016 RX OINTMENT TOPICAL April 3, 2026 ADDITION OF A ONCE DAILY DOSING REGIMEN

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Phosphodiesterase 4 Enzyme INHIBITOR IC50 6.31 SCIENTIFIC LITERATURE DRUG LABEL
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Enzyme IC50 5.21 CHEMBL
High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A Enzyme IC50 6.14 CHEMBL
Beta-lactamase Enzyme IC50 6.17 CHEMBL

External reference:

IDSource
Q2R47HGR7P UNII
4036360 VANDF
C4301781 UMLSCUI
CHEBI:134677 CHEBI
CHEMBL484785 ChEMBL_ID
44591583 PUBCHEM_CID
DB05219 DRUGBANK_ID
D10873 KEGG_DRUG
10024 INN_ID
C543085 MESH_SUPPLEMENTAL_RECORD_UI
9151 IUPHAR_LIGAND_ID
724007009 SNOMEDCT_US
763593001 SNOMEDCT_US
248463 MMSL
32196 MMSL
017053 NDDF
1865953 RXNORM

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Staquis HUMAN PRESCRIPTION DRUG LABEL 1 0009-2211 OINTMENT 20 mg TOPICAL Export only 1 sections
Eucrisa HUMAN PRESCRIPTION DRUG LABEL 1 55724-211 OINTMENT 20 mg TOPICAL NDA 25 sections