Identification

Name
Crisaborole
Accession Number
DB05219
Type
Small Molecule
Groups
Approved
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
AN-2728 / AN2728
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EucrisaOintment20 mg/gTopicalAnacor Pharmaceuticals, Inc.2017-01-30Not applicableUs
Categories
UNII
Q2R47HGR7P
CAS number
906673-24-3
Weight
Average: 251.05
Monoisotopic: 251.075373
Chemical Formula
C14H10BNO3
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

Pharmacology

Indication

Intended for the topical treatment of mild to moderate atopic dermatitis in patients 2 years of age and older.

Structured Indications
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.

TargetActionsOrganism
UcAMP-specific 3',5'-cyclic phosphodiesterase 4A
inhibitor
Human
UcAMP-specific 3',5'-cyclic phosphodiesterase 4B
inhibitor
Human
UcAMP-specific 3',5'-cyclic phosphodiesterase 4C
inhibitor
Human
UcAMP-specific 3',5'-cyclic phosphodiesterase 4D
inhibitor
Human
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
Toxicity

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.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AceclofenacThe metabolism of Aceclofenac can be decreased when combined with Crisaborole.Approved, Investigational
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Crisaborole.Approved
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Crisaborole.Approved
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be decreased when combined with Crisaborole.Approved, Vet Approved
AlmotriptanThe metabolism of Almotriptan can be decreased when combined with Crisaborole.Approved, Investigational
AlosetronThe metabolism of Alosetron can be decreased when combined with Crisaborole.Approved, Withdrawn
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Crisaborole.Approved, Illicit, Investigational
AminophenazoneThe metabolism of Aminophenazone can be decreased when combined with Crisaborole.Approved, Withdrawn
AmiodaroneThe metabolism of Amiodarone can be decreased when combined with Crisaborole.Approved, Investigational
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Crisaborole.Approved
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Crisaborole.Approved, Investigational
AmprenavirThe metabolism of Amprenavir can be decreased when combined with Crisaborole.Approved
AntipyrineThe metabolism of Antipyrine can be decreased when combined with Crisaborole.Approved
ApixabanThe metabolism of Apixaban can be decreased when combined with Crisaborole.Approved
Arachidonic AcidThe metabolism of Arachidonic Acid can be decreased when combined with Crisaborole.Experimental
ArformoterolThe metabolism of Arformoterol can be decreased when combined with Crisaborole.Approved, Investigational
ArtemetherThe metabolism of Artemether can be decreased when combined with Crisaborole.Approved
AtazanavirThe metabolism of Atazanavir can be decreased when combined with Crisaborole.Approved, Investigational
AtorvastatinThe metabolism of Atorvastatin can be decreased when combined with Crisaborole.Approved
AzelastineThe metabolism of Azelastine can be decreased when combined with Crisaborole.Approved
Benzyl alcoholThe metabolism of Benzyl alcohol can be decreased when combined with Crisaborole.Approved
BeraprostThe metabolism of Beraprost can be decreased when combined with Crisaborole.Investigational
BexaroteneThe metabolism of Bexarotene can be decreased when combined with Crisaborole.Approved, Investigational
BortezomibThe metabolism of Bortezomib can be decreased when combined with Crisaborole.Approved, Investigational
BosentanThe serum concentration of Bosentan can be increased when it is combined with Crisaborole.Approved, Investigational
BrivaracetamThe metabolism of Brivaracetam can be decreased when combined with Crisaborole.Approved, Investigational
BrompheniramineThe metabolism of Brompheniramine can be decreased when combined with Crisaborole.Approved
BuprenorphineThe metabolism of Buprenorphine can be decreased when combined with Crisaborole.Approved, Illicit, Investigational, Vet Approved
BupropionThe metabolism of Bupropion can be decreased when combined with Crisaborole.Approved
CabazitaxelThe metabolism of Cabazitaxel can be decreased when combined with Crisaborole.Approved
CabozantinibThe metabolism of Cabozantinib can be decreased when combined with Crisaborole.Approved
CaffeineThe metabolism of Caffeine can be decreased when combined with Crisaborole.Approved
Candesartan cilexetilThe metabolism of Candesartan can be decreased when combined with Crisaborole.Approved
CarbamazepineThe metabolism of Carbamazepine can be decreased when combined with Crisaborole.Approved, Investigational
CarbinoxamineThe metabolism of Carbinoxamine can be decreased when combined with Crisaborole.Approved
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Crisaborole.Approved, Investigational
CelecoxibThe metabolism of Celecoxib can be decreased when combined with Crisaborole.Approved, Investigational
CerivastatinThe metabolism of Cerivastatin can be decreased when combined with Crisaborole.Withdrawn
ChloroquineThe metabolism of Chloroquine can be decreased when combined with Crisaborole.Approved, Vet Approved
ChlorpropamideThe metabolism of Chlorpropamide can be decreased when combined with Crisaborole.Approved
CinnarizineThe metabolism of Cinnarizine can be decreased when combined with Crisaborole.Approved, Investigational
CisaprideThe metabolism of Cisapride can be decreased when combined with Crisaborole.Approved, Investigational, Withdrawn
ClopidogrelThe metabolism of Clopidogrel can be decreased when combined with Crisaborole.Approved, Nutraceutical
ClozapineThe metabolism of Clozapine can be decreased when combined with Crisaborole.Approved
CyclophosphamideThe metabolism of Cyclophosphamide can be decreased when combined with Crisaborole.Approved, Investigational
DabrafenibThe metabolism of Dabrafenib can be decreased when combined with Crisaborole.Approved
DapagliflozinThe metabolism of Dapagliflozin can be decreased when combined with Crisaborole.Approved
DapsoneThe metabolism of Dapsone can be decreased when combined with Crisaborole.Approved, Investigational
DasabuvirThe metabolism of Dasabuvir can be decreased when combined with Crisaborole.Approved
DextromethorphanThe metabolism of Dextromethorphan can be decreased when combined with Crisaborole.Approved
DiazepamThe metabolism of Diazepam can be decreased when combined with Crisaborole.Approved, Illicit, Vet Approved
DiclofenacThe metabolism of Diclofenac can be decreased when combined with Crisaborole.Approved, Vet Approved
DicoumarolThe metabolism of Dicoumarol can be decreased when combined with Crisaborole.Approved
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Crisaborole.Approved
DiphenhydramineThe metabolism of Diphenhydramine can be decreased when combined with Crisaborole.Approved
DoconexentThe metabolism of Doconexent can be decreased when combined with Crisaborole.Approved, Investigational
DolasetronThe metabolism of Dolasetron can be decreased when combined with Crisaborole.Approved
DomperidoneThe metabolism of Domperidone can be decreased when combined with Crisaborole.Approved, Investigational, Vet Approved
DonepezilThe metabolism of Donepezil can be decreased when combined with Crisaborole.Approved
DopamineThe metabolism of Dopamine can be decreased when combined with Crisaborole.Approved
DorzolamideThe metabolism of Dorzolamide can be decreased when combined with Crisaborole.Approved
DoxepinThe metabolism of Doxepin can be decreased when combined with Crisaborole.Approved
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Crisaborole.Approved, Illicit
EletriptanThe metabolism of Eletriptan can be decreased when combined with Crisaborole.Approved, Investigational
EltrombopagThe metabolism of Eltrombopag can be decreased when combined with Crisaborole.Approved
EnasidenibThe metabolism of Enasidenib can be decreased when combined with Crisaborole.Approved
EnzalutamideThe metabolism of Enzalutamide can be decreased when combined with Crisaborole.Approved
EpoprostenolThe metabolism of Epoprostenol can be decreased when combined with Crisaborole.Approved
ErlotinibThe metabolism of Erlotinib can be decreased when combined with Crisaborole.Approved, Investigational
EstradiolThe metabolism of Estradiol can be decreased when combined with Crisaborole.Approved, Investigational, Vet Approved
EstroneThe metabolism of Estrone can be decreased when combined with Crisaborole.Approved
EszopicloneThe metabolism of Eszopiclone can be decreased when combined with Crisaborole.Approved
EtodolacThe metabolism of Etodolac can be decreased when combined with Crisaborole.Approved, Investigational, Vet Approved
EtoricoxibThe metabolism of Etoricoxib can be decreased when combined with Crisaborole.Approved, Investigational
EtravirineThe metabolism of Etravirine can be decreased when combined with Crisaborole.Approved
FlunarizineThe metabolism of Flunarizine can be decreased when combined with Crisaborole.Approved
FlunitrazepamThe metabolism of Flunitrazepam can be decreased when combined with Crisaborole.Approved, Illicit
FluorouracilThe metabolism of Fluorouracil can be decreased when combined with Crisaborole.Approved
FluoxetineThe metabolism of Fluoxetine can be decreased when combined with Crisaborole.Approved, Vet Approved
FlurbiprofenThe metabolism of Flurbiprofen can be decreased when combined with Crisaborole.Approved, Investigational
FluvastatinThe metabolism of Fluvastatin can be decreased when combined with Crisaborole.Approved
FormoterolThe metabolism of Formoterol can be decreased when combined with Crisaborole.Approved, Investigational
FosphenytoinThe metabolism of Fosphenytoin can be decreased when combined with Crisaborole.Approved
GavestinelThe metabolism of Gavestinel can be decreased when combined with Crisaborole.Investigational
GliclazideThe metabolism of Gliclazide can be decreased when combined with Crisaborole.Approved
GlimepirideThe metabolism of Glimepiride can be decreased when combined with Crisaborole.Approved
GlipizideThe metabolism of Glipizide can be decreased when combined with Crisaborole.Approved
GlyburideThe metabolism of Glyburide can be decreased when combined with Crisaborole.Approved
GuanfacineThe metabolism of Guanfacine can be decreased when combined with Crisaborole.Approved, Investigational
HalofantrineThe metabolism of Halofantrine can be decreased when combined with Crisaborole.Approved
HaloperidolThe metabolism of Haloperidol can be decreased when combined with Crisaborole.Approved
HalothaneThe metabolism of Halothane can be decreased when combined with Crisaborole.Approved, Vet Approved
HexobarbitalThe metabolism of Hexobarbital can be decreased when combined with Crisaborole.Approved
HistamineThe metabolism of Histamine can be decreased when combined with Crisaborole.Approved, Investigational
HydromorphoneThe metabolism of Hydromorphone can be decreased when combined with Crisaborole.Approved, Illicit
IbuprofenThe metabolism of Ibuprofen can be decreased when combined with Crisaborole.Approved
IdarubicinThe metabolism of Idarubicin can be decreased when combined with Crisaborole.Approved
IfosfamideThe metabolism of Ifosfamide can be decreased when combined with Crisaborole.Approved
ImatinibThe metabolism of Imatinib can be decreased when combined with Crisaborole.Approved
indisulamThe metabolism of indisulam can be decreased when combined with Crisaborole.Investigational
IndomethacinThe metabolism of Indomethacin can be decreased when combined with Crisaborole.Approved, Investigational
IrbesartanThe metabolism of Irbesartan can be decreased when combined with Crisaborole.Approved, Investigational
IxazomibThe metabolism of Ixazomib can be decreased when combined with Crisaborole.Approved
KetamineThe metabolism of Ketamine can be decreased when combined with Crisaborole.Approved, Vet Approved
KetobemidoneThe metabolism of Ketobemidone can be decreased when combined with Crisaborole.Approved, Investigational
KetoprofenThe metabolism of Ketoprofen can be decreased when combined with Crisaborole.Approved, Vet Approved
LansoprazoleThe metabolism of Lansoprazole can be decreased when combined with Crisaborole.Approved, Investigational
LapatinibThe metabolism of Lapatinib can be decreased when combined with Crisaborole.Approved, Investigational
LeflunomideThe metabolism of Leflunomide can be decreased when combined with Crisaborole.Approved, Investigational
LesinuradThe metabolism of Lesinurad can be decreased when combined with Crisaborole.Approved
LevomilnacipranThe metabolism of Levomilnacipran can be decreased when combined with Crisaborole.Approved
LicofeloneThe metabolism of Licofelone can be decreased when combined with Crisaborole.Investigational
LidocaineThe metabolism of Lidocaine can be decreased when combined with Crisaborole.Approved, Vet Approved
LoperamideThe metabolism of Loperamide can be decreased when combined with Crisaborole.Approved
LoratadineThe metabolism of Loratadine can be decreased when combined with Crisaborole.Approved
LornoxicamThe metabolism of Lornoxicam can be decreased when combined with Crisaborole.Approved, Investigational
LosartanThe metabolism of Losartan can be decreased when combined with Crisaborole.Approved
LumiracoxibThe metabolism of Lumiracoxib can be decreased when combined with Crisaborole.Approved, Investigational
Mefenamic acidThe metabolism of Mefenamic acid can be decreased when combined with Crisaborole.Approved
MelatoninThe metabolism of Melatonin can be decreased when combined with Crisaborole.Approved, Nutraceutical, Vet Approved
MeloxicamThe metabolism of Meloxicam can be decreased when combined with Crisaborole.Approved, Vet Approved
MephenytoinThe metabolism of Mephenytoin can be decreased when combined with Crisaborole.Investigational, Withdrawn
MestranolThe metabolism of Mestranol can be decreased when combined with Crisaborole.Approved
MethadoneThe metabolism of Methadone can be decreased when combined with Crisaborole.Approved
MethoxyfluraneThe metabolism of Methoxyflurane can be decreased when combined with Crisaborole.Approved, Investigational, Vet Approved
MetronidazoleThe metabolism of Metronidazole can be decreased when combined with Crisaborole.Approved
MirtazapineThe metabolism of Mirtazapine can be decreased when combined with Crisaborole.Approved
MoclobemideThe metabolism of Moclobemide can be decreased when combined with Crisaborole.Approved
MontelukastThe metabolism of Montelukast can be decreased when combined with Crisaborole.Approved
MorphineThe metabolism of Morphine can be decreased when combined with Crisaborole.Approved, Investigational
muraglitazarThe metabolism of muraglitazar can be decreased when combined with Crisaborole.Investigational
Mycophenolate mofetilThe metabolism of Mycophenolate mofetil can be decreased when combined with Crisaborole.Approved, Investigational
NaloxoneThe metabolism of Naloxone can be decreased when combined with Crisaborole.Approved, Vet Approved
NaproxenThe metabolism of Naproxen can be decreased when combined with Crisaborole.Approved, Vet Approved
NateglinideThe metabolism of Nateglinide can be decreased when combined with Crisaborole.Approved, Investigational
NetupitantThe metabolism of Netupitant can be decreased when combined with Crisaborole.Approved
NevirapineThe metabolism of Nevirapine can be decreased when combined with Crisaborole.Approved
NicardipineThe metabolism of Nicardipine can be decreased when combined with Crisaborole.Approved
NiclosamideThe metabolism of Niclosamide can be decreased when combined with Crisaborole.Approved, Investigational, Vet Approved
NicotineThe metabolism of Nicotine can be decreased when combined with Crisaborole.Approved
NortriptylineThe metabolism of Nortriptyline can be decreased when combined with Crisaborole.Approved
OdanacatibThe metabolism of Odanacatib can be decreased when combined with Crisaborole.Investigational
OlodaterolThe metabolism of Olodaterol can be decreased when combined with Crisaborole.Approved
OmbitasvirThe metabolism of Ombitasvir can be decreased when combined with Crisaborole.Approved
OmeprazoleThe metabolism of Omeprazole can be decreased when combined with Crisaborole.Approved, Investigational, Vet Approved
OndansetronThe metabolism of Ondansetron can be decreased when combined with Crisaborole.Approved
OspemifeneThe metabolism of Ospemifene can be decreased when combined with Crisaborole.Approved
OxaprozinThe metabolism of Oxaprozin can be decreased when combined with Crisaborole.Approved
PaclitaxelThe metabolism of Paclitaxel can be decreased when combined with Crisaborole.Approved, Vet Approved
ParamethadioneThe metabolism of Paramethadione can be decreased when combined with Crisaborole.Approved
ParecoxibThe metabolism of Parecoxib can be decreased when combined with Crisaborole.Approved
PazopanibThe metabolism of Pazopanib can be decreased when combined with Crisaborole.Approved
PentamidineThe metabolism of Pentamidine can be decreased when combined with Crisaborole.Approved
PerospironeThe metabolism of Perospirone can be decreased when combined with Crisaborole.Approved
PerphenazineThe metabolism of Perphenazine can be decreased when combined with Crisaborole.Approved
PhenacetinThe metabolism of Phenacetin can be decreased when combined with Crisaborole.Withdrawn
PhenobarbitalThe metabolism of Phenobarbital can be decreased when combined with Crisaborole.Approved
PhenprocoumonThe metabolism of Phenprocoumon can be decreased when combined with Crisaborole.Approved, Investigational
PhenylbutazoneThe metabolism of Phenylbutazone can be decreased when combined with Crisaborole.Approved, Vet Approved
PhenytoinThe metabolism of Phenytoin can be decreased when combined with Crisaborole.Approved, Vet Approved
PioglitazoneThe metabolism of Pioglitazone can be decreased when combined with Crisaborole.Approved, Investigational
PiroxicamThe metabolism of Piroxicam can be decreased when combined with Crisaborole.Approved, Investigational
PitavastatinThe metabolism of Pitavastatin can be decreased when combined with Crisaborole.Approved
PonatinibThe metabolism of Ponatinib can be decreased when combined with Crisaborole.Approved
PrasugrelThe metabolism of Prasugrel can be decreased when combined with Crisaborole.Approved
PravastatinThe metabolism of Pravastatin can be decreased when combined with Crisaborole.Approved
ProgesteroneThe metabolism of Progesterone can be decreased when combined with Crisaborole.Approved, Vet Approved
ProguanilThe metabolism of Proguanil can be decreased when combined with Crisaborole.Approved
PromazineThe metabolism of Promazine can be decreased when combined with Crisaborole.Approved, Vet Approved
PropofolThe metabolism of Propofol can be decreased when combined with Crisaborole.Approved, Investigational, Vet Approved
QuazepamThe metabolism of Quazepam can be decreased when combined with Crisaborole.Approved, Illicit
QuinidineThe metabolism of Quinidine can be decreased when combined with Crisaborole.Approved
QuinineThe metabolism of Quinine can be decreased when combined with Crisaborole.Approved
RepaglinideThe metabolism of Repaglinide can be decreased when combined with Crisaborole.Approved, Investigational
RifampicinThe metabolism of Rifampicin can be decreased when combined with Crisaborole.Approved
RiociguatThe metabolism of Riociguat can be decreased when combined with Crisaborole.Approved
RofecoxibThe metabolism of Rofecoxib can be decreased when combined with Crisaborole.Investigational, Withdrawn
RosiglitazoneThe metabolism of Rosiglitazone can be decreased when combined with Crisaborole.Approved, Investigational
RosuvastatinThe metabolism of Rosuvastatin can be decreased when combined with Crisaborole.Approved
RupatadineThe metabolism of Rupatadine can be decreased when combined with Crisaborole.Approved
Salicylic acidThe metabolism of Salicylic acid can be decreased when combined with Crisaborole.Approved, Vet Approved
SelegilineThe metabolism of Selegiline can be decreased when combined with Crisaborole.Approved, Investigational, Vet Approved
SelexipagThe metabolism of Selexipag can be decreased when combined with Crisaborole.Approved
SeratrodastThe metabolism of Seratrodast can be decreased when combined with Crisaborole.Approved
SertralineThe metabolism of Sertraline can be decreased when combined with Crisaborole.Approved
SildenafilThe metabolism of Sildenafil can be decreased when combined with Crisaborole.Approved, Investigational
SimvastatinThe metabolism of Simvastatin can be decreased when combined with Crisaborole.Approved
SitagliptinThe metabolism of Sitagliptin can be decreased when combined with Crisaborole.Approved, Investigational
SitaxentanThe metabolism of Sitaxentan can be decreased when combined with Crisaborole.Approved, Investigational, Withdrawn
SorafenibThe metabolism of Sorafenib can be decreased when combined with Crisaborole.Approved, Investigational
SulfadiazineThe metabolism of Sulfadiazine can be decreased when combined with Crisaborole.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Sulfamethoxazole can be decreased when combined with Crisaborole.Approved
SulfamoxoleThe metabolism of Sulfamoxole can be decreased when combined with Crisaborole.Approved
SulfinpyrazoneThe metabolism of Sulfinpyrazone can be decreased when combined with Crisaborole.Approved
SulfisoxazoleThe metabolism of Sulfisoxazole can be decreased when combined with Crisaborole.Approved, Vet Approved
SuprofenThe metabolism of Suprofen can be decreased when combined with Crisaborole.Approved, Withdrawn
TamoxifenThe metabolism of Tamoxifen can be decreased when combined with Crisaborole.Approved
TapentadolThe metabolism of Tapentadol can be decreased when combined with Crisaborole.Approved
TazaroteneThe metabolism of Tazarotene can be decreased when combined with Crisaborole.Approved, Investigational
TemazepamThe metabolism of Temazepam can be decreased when combined with Crisaborole.Approved
TenoxicamThe metabolism of Tenoxicam can be decreased when combined with Crisaborole.Approved
TerbinafineThe metabolism of Terbinafine can be decreased when combined with Crisaborole.Approved, Investigational, Vet Approved
TerfenadineThe metabolism of Terfenadine can be decreased when combined with Crisaborole.Withdrawn
TestosteroneThe metabolism of Testosterone can be decreased when combined with Crisaborole.Approved, Investigational
ThalidomideThe metabolism of Thalidomide can be decreased when combined with Crisaborole.Approved, Investigational, Withdrawn
TheophyllineThe metabolism of Theophylline can be decreased when combined with Crisaborole.Approved
ThiamylalThe metabolism of Thiamylal can be decreased when combined with Crisaborole.Approved, Vet Approved
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Crisaborole.Approved
TolbutamideThe metabolism of Tolbutamide can be decreased when combined with Crisaborole.Approved
TolterodineThe metabolism of Tolterodine can be decreased when combined with Crisaborole.Approved, Investigational
TorasemideThe metabolism of Torasemide can be decreased when combined with Crisaborole.Approved
TrabectedinThe metabolism of Trabectedin can be decreased when combined with Crisaborole.Approved, Investigational
TreprostinilThe metabolism of Treprostinil can be decreased when combined with Crisaborole.Approved, Investigational
TretinoinThe metabolism of Tretinoin can be decreased when combined with Crisaborole.Approved, Investigational, Nutraceutical
TrimethadioneThe metabolism of Trimethadione can be decreased when combined with Crisaborole.Approved
TrimethoprimThe metabolism of Trimethoprim can be decreased when combined with Crisaborole.Approved, Vet Approved
TrimipramineThe metabolism of Trimipramine can be decreased when combined with Crisaborole.Approved
TroglitazoneThe metabolism of Troglitazone can be decreased when combined with Crisaborole.Investigational, Withdrawn
ValdecoxibThe metabolism of Valdecoxib can be decreased when combined with Crisaborole.Investigational, Withdrawn
Valproic AcidThe metabolism of Valproic Acid can be decreased when combined with Crisaborole.Approved, Investigational
ValsartanThe metabolism of Valsartan can be decreased when combined with Crisaborole.Approved, Investigational
VelpatasvirThe metabolism of Velpatasvir can be decreased when combined with Crisaborole.Approved
VenlafaxineThe metabolism of Venlafaxine can be decreased when combined with Crisaborole.Approved
VerapamilThe metabolism of Verapamil can be decreased when combined with Crisaborole.Approved
VicrivirocThe metabolism of Vicriviroc can be decreased when combined with Crisaborole.Investigational
VismodegibThe metabolism of Vismodegib can be decreased when combined with Crisaborole.Approved
VoriconazoleThe metabolism of Voriconazole can be decreased when combined with Crisaborole.Approved, Investigational
VortioxetineThe metabolism of Vortioxetine can be decreased when combined with Crisaborole.Approved
VoxilaprevirThe metabolism of Voxilaprevir can be decreased when combined with Crisaborole.Approved
WarfarinThe metabolism of Warfarin can be decreased when combined with Crisaborole.Approved
XimelagatranThe metabolism of Ximelagatran can be decreased when combined with Crisaborole.Approved, Investigational, Withdrawn
ZafirlukastThe metabolism of Zafirlukast can be decreased when combined with Crisaborole.Approved, Investigational
ZalcitabineThe metabolism of Zalcitabine can be decreased when combined with Crisaborole.Approved, Investigational
ZaltoprofenThe metabolism of Zaltoprofen can be decreased when combined with Crisaborole.Approved, Investigational
ZidovudineThe metabolism of Zidovudine can be decreased when combined with Crisaborole.Approved
ZileutonThe metabolism of Zileuton can be decreased when combined with Crisaborole.Approved, Investigational, Withdrawn
ZolpidemThe metabolism of Zolpidem can be decreased when combined with Crisaborole.Approved
ZopicloneThe metabolism of Zopiclone can be decreased when combined with Crisaborole.Approved
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:27417017]
  2. 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. [PubMed:28492291]
  3. 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. [PubMed:27335049]
  4. 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. [PubMed:24852768]
External Links
KEGG Drug
D10873
PubChem Compound
44591583
PubChem Substance
175426957
ChemSpider
24701949
BindingDB
50277665
ChEBI
134677
ChEMBL
CHEMBL484785
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
PhaseStatusPurposeConditionsCount
1CompletedTreatmentPsoriasis1
2CompletedTreatmentPsoriasis3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
OintmentTopical20 mg/g
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8039451No2006-06-112026-06-11Us
US8501712No2007-02-162027-02-16Us
US8168614No2010-01-202030-01-20Us
US9682092No2007-02-162027-02-16Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsolubleFDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.0234 mg/mLALOGPS
logP2.6ALOGPS
logP3.34ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)8.95ChemAxon
pKa (Strongest Basic)-3.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area62.48 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity65.6 m3·mol-1ChemAxon
Polarizability25.9 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9563
Blood Brain Barrier+0.9383
Caco-2 permeable-0.5845
P-glycoprotein substrateNon-substrate0.547
P-glycoprotein inhibitor INon-inhibitor0.8845
P-glycoprotein inhibitor IINon-inhibitor0.8936
Renal organic cation transporterNon-inhibitor0.6515
CYP450 2C9 substrateNon-substrate0.7986
CYP450 2D6 substrateNon-substrate0.7423
CYP450 3A4 substrateNon-substrate0.6599
CYP450 1A2 substrateInhibitor0.5611
CYP450 2C9 inhibitorNon-inhibitor0.6637
CYP450 2D6 inhibitorNon-inhibitor0.706
CYP450 2C19 inhibitorNon-inhibitor0.5344
CYP450 3A4 inhibitorNon-inhibitor0.8253
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.771
Ames testAMES toxic0.5445
CarcinogenicityNon-carcinogens0.8567
BiodegradationNot ready biodegradable0.9645
Rat acute toxicity2.4979 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7405
hERG inhibition (predictor II)Inhibitor0.5739
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Diaryl ether / Phenoxy compound / Benzonitrile / Phenol ether / Monocyclic benzene moiety / Benzenoid / Boronic acid ester / 1,2-oxaborole derivative / Boronic acid derivative / Oxacycle
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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
  1. 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. [PubMed:22841723]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:22841723]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:22841723]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:22841723]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
Kind
Protein
Organism
Human
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
Human
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
Human
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 on October 21, 2007 16:24 / Updated on November 09, 2017 03:50