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

Stem definitionDrug idCAS RN
Janus kinase inhibitors, antineoplastics 5504 1622902-68-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • abrocitinib
  • cibinqo
  • PF-04965842
Abrocitinib is a Janus kinase (JAK)1 inhibitor. JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs) which modulate intracellular activity including gene expression. Inhibition of JAK1 modulates the signalling pathways by preventing the phosphorylation and activation of STATs. It is used for treating adults with moderate to severe atopic dermatitis (also known as eczema, when the skin is itchy, red and dry).
  • Molecular weight: 323.42
  • Formula: C14H21N5O2S
  • CLOGP: 2.54
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 2
  • TPSA: 90.98
  • ALOGS: -2.89
  • ROTB: 5
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.15 g O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.169 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.911 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 39.264 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 4.943 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 36.260 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 55.790 % High 1
herg hERG pIC50 4.628 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.754 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 7.015 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 29.760 % High 1
kinase-safety-class AAK1,ACVR2A,ACVR2B,ACVRL1,ALK,AURKA,AURKB,AURKC,AXL,BLK,BRAF,CAMK2A,CAMK2B,CAMK2D,CAMK2G,CDK1,CDK14,CDK16,CDK19,CDK3,CDK5,CDK7,CDK9,CHEK1,CLK1,CLK2,CLK4,CSF1R,DDR1,DYRK1A,DYRK1B,EGFR,EIF2AK3,EPHA2,ERBB2,FGFR1,FLT3,GAK,GRK1,GRK2,GRK3,GSK3B,HASPIN,IGF1R,IKBKB,IRAK1,IRAK3,ITK,JAK1,JAK2,JAK3,KIT,LCK,LRRK2,MAP2K1,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K2,MAP3K21,MAP3K7,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK1,MAPK10,MAPK3,MAPK7,MAPK9,MARK3,MARK4,MELK,MET,NTRK1,PAK4,PDK1,PDK2,PIK3CD,PRKAA1,PRKAA2,PRKACA,PRKCA,PRKCD,PRKDC,PRKG1,ROCK1,ROCK2,RPS6KA1,SGK1,SIK2,SIK3,SRC,STK33,SYK,TEK,TTK,ULK1,ULK2 100
kinase-selectivity-class AAK1,ACVR2B,AKT1,AURKA,AURKB,AXL,BRAF,CAMK2B,CAMK2D,CDK1,CDK16,CDK2,CDK7,CDK8,CDK9,CLK2,CLK4,DYRK1A,DYRK1B,EGFR,FLT3,GSK3B,HASPIN,IRAK1,IRAK3,JAK1,JAK2,JAK3,KDR,LRRK2,MAP2K6,MAP3K10,MAP3K21,MAP4K1,MAP4K3,MAPK1,MARK4,MELK,NTRK1,PDK1,PRKACA,PRKCD,ROCK1,ROCK2,SIK2,SIK3,STK17A,STK33,SYK,ULK1 50
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 4.989 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 9.528 High 1
mh-clint Mouse hepatocyte intrinsic clearance 20.559 High 1
mppb Mouse plasma protein binding (% unbound) 34 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 12.647 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 49.370 % High 1
rat-kpuu-brain Rat brain Kpuu 0.127 % High 1
rh-clint Rat hepatocyte intrinsic clearance 5.236 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 77.330 % High 1
rppb Rat plasma protein binding (% unbound) 27.040 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 99.541 uM High 1

Approvals:

DateAgencyCompanyOrphan
Sept. 27, 2021 PMDA PFIZER JAPAN INC.
Dec. 9, 2021 EMA PFIZER EUROPE MA EEIG
Jan. 14, 2022 FDA PFIZER 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
Condition aggravated 191.60 30.16 135 1943 595410 90030959
Drug ineffective 169.61 30.16 180 1898 1384118 89242251
Therapeutic product effect incomplete 168.86 30.16 84 1994 193812 90432557
Eczema herpeticum 112.70 30.16 16 2062 209 90626160
Acne 101.28 30.16 34 2044 28473 90597896
Dermatitis atopic 79.42 30.16 27 2051 23445 90602924
Off label use 74.33 30.16 107 1971 1102145 89524224
Pruritus 59.08 30.16 67 2011 541458 90084911
Cutaneous T-cell lymphoma 57.41 30.16 12 2066 1608 90624761
Therapeutic response unexpected 43.46 30.16 17 2061 21863 90604506
Eczema 40.20 30.16 21 2057 52849 90573520
Skin exfoliation 37.92 30.16 22 2056 67891 90558478
Lipids increased 31.08 30.16 7 2071 1325 90625044
Oral herpes 30.39 30.16 15 2063 33509 90592860

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
Therapeutic product effect incomplete 173.97 39.84 74 1578 70865 42548818
Condition aggravated 137.14 39.84 98 1554 260656 42359027
Eczema herpeticum 136.07 39.84 21 1631 287 42619396
Drug ineffective 122.29 39.84 134 1518 630063 41989620
Pruritus 74.42 39.84 60 1592 188711 42430972
Off label use 61.89 39.84 97 1555 638238 41981445
Dermatitis atopic 55.16 39.84 20 1632 12384 42607299
Lipids increased 54.61 39.84 12 1640 1200 42618483
Eczema 50.00 39.84 25 1627 34061 42585622

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
Therapeutic product effect incomplete 322.53 32.08 150 3243 223655 110362251
Condition aggravated 307.29 32.08 219 3174 734617 109851289
Drug ineffective 222.65 32.08 250 3143 1520290 109065616
Eczema herpeticum 190.76 32.08 29 3364 457 110585449
Off label use 118.46 32.08 183 3210 1500002 109085904
Pruritus 103.69 32.08 107 3286 581453 110004453
Dermatitis atopic 83.93 32.08 31 3362 25510 110560396
Acne 79.18 32.08 32 3361 33488 110552418
Eczema 66.72 32.08 36 3357 72257 110513649
Sleep disorder 57.42 32.08 48 3345 198596 110387310
Cutaneous T-cell lymphoma 49.92 32.08 13 3380 3371 110582535
Dry skin 41.83 32.08 31 3362 107622 110478284
Drug effective for unapproved indication 38.59 32.08 15 3378 14152 110571754
Skin exfoliation 38.05 32.08 27 3366 87624 110498282
Herpes zoster 37.23 32.08 29 3364 108350 110477556
Therapeutic response unexpected 34.13 32.08 16 3377 23827 110562079
Product prescribing error 32.46 32.08 20 3373 51311 110534595

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC D11AH08 DERMATOLOGICALS
OTHER DERMATOLOGICAL PREPARATIONS
OTHER DERMATOLOGICAL PREPARATIONS
Agents for dermatitis, excluding corticosteroids
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000190857 Janus Kinase Inhibitors
FDA EPC N0000190858 Janus Kinase Inhibitor
CHEBI has role CHEBI:35526 hypoglycemic agent
CHEBI has role CHEBI:50177 dermatologic drug
CHEBI has role CHEBI:50748 antipsoriatic
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

D11AH Agents for dermatitis, excluding corticosteroids 11 drugs
alitretinoincrisaborolecromoglicic 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

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
100MG CIBINQO PFIZER N213871 Jan. 14, 2022 RX TABLET ORAL 9549929 Feb. 19, 2034 TREATMENT OF ADULTS WITH REFRACTORY, MODERATE-TO-SEVERE ATOPIC DERMATITIS NOT ADEQUATELY CONTROLLED WITH OTHER SYSTEMIC DRUG PRODUCTS OR WHEN USE OF THOSE THERAPIES IS INADVISABLE
200MG CIBINQO PFIZER N213871 Jan. 14, 2022 RX TABLET ORAL 9549929 Feb. 19, 2034 TREATMENT OF ADULTS WITH REFRACTORY, MODERATE-TO-SEVERE ATOPIC DERMATITIS NOT ADEQUATELY CONTROLLED WITH OTHER SYSTEMIC DRUG PRODUCTS OR WHEN USE OF THOSE THERAPIES IS INADVISABLE
50MG CIBINQO PFIZER N213871 Jan. 14, 2022 RX TABLET ORAL 9549929 Feb. 19, 2034 TREATMENT OF ADULTS WITH REFRACTORY, MODERATE-TO-SEVERE ATOPIC DERMATITIS NOT ADEQUATELY CONTROLLED WITH OTHER SYSTEMIC DRUG PRODUCTS OR WHEN USE OF THOSE THERAPIES IS INADVISABLE

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG CIBINQO PFIZER N213871 Jan. 14, 2022 RX TABLET ORAL Feb. 9, 2026 NEW PATIENT POPULATION
200MG CIBINQO PFIZER N213871 Jan. 14, 2022 RX TABLET ORAL Feb. 9, 2026 NEW PATIENT POPULATION
50MG CIBINQO PFIZER N213871 Jan. 14, 2022 RX TABLET ORAL Feb. 9, 2026 NEW PATIENT POPULATION
100MG CIBINQO PFIZER N213871 Jan. 14, 2022 RX TABLET ORAL Jan. 14, 2027 NEW CHEMICAL ENTITY
200MG CIBINQO PFIZER N213871 Jan. 14, 2022 RX TABLET ORAL Jan. 14, 2027 NEW CHEMICAL ENTITY
50MG CIBINQO PFIZER N213871 Jan. 14, 2022 RX TABLET ORAL Jan. 14, 2027 NEW CHEMICAL ENTITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Tyrosine-protein kinase JAK1 Kinase INHIBITOR IC50 7.54 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Tyrosine-protein kinase JAK3 Kinase IC50 6.32 CHEMBL
Amine oxidase [flavin-containing] A Enzyme IC50 5.22 CHEMBL
Vascular endothelial growth factor receptor 2 Kinase IC50 5.92 CHEMBL
Non-receptor tyrosine-protein kinase TYK2 Kinase IC50 6.80 CHEMBL
Tyrosine-protein kinase JAK2 Kinase INHIBITOR IC50 6.10 SCIENTIFIC LITERATURE

External reference:

IDSource
CHEBI:755682 CHEBI
CHEMBL3655081 ChEMBL_ID
C000634427 MESH_SUPPLEMENTAL_RECORD_UI
9991 IUPHAR_LIGAND_ID
DB14973 DRUGBANK_ID
1287408008 SNOMEDCT_US
1287482006 SNOMEDCT_US
4041157 VANDF
C5139788 UMLSCUI
D11400 KEGG_DRUG
11012 INN_ID
78323835 PUBCHEM_CID
353076 MMSL
40053 MMSL
d09824 MMSL
018933 NDDF
73SM5SF3OR UNII
2591476 RXNORM
73SM5SF3OR INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Cibinqo HUMAN PRESCRIPTION DRUG LABEL 1 0069-0235 TABLET, FILM COATED 50 mg ORAL NDA 34 sections
Cibinqo HUMAN PRESCRIPTION DRUG LABEL 1 0069-0335 TABLET, FILM COATED 100 mg ORAL NDA 34 sections
Cibinqo HUMAN PRESCRIPTION DRUG LABEL 1 0069-0435 TABLET, FILM COATED 200 mg ORAL NDA 34 sections
CIBINQO HUMAN PRESCRIPTION DRUG LABEL 1 63539-236 TABLET, FILM COATED 50 mg ORAL NDA 34 sections
CIBINQO HUMAN PRESCRIPTION DRUG LABEL 1 63539-336 TABLET, FILM COATED 100 mg ORAL NDA 34 sections
CIBINQO HUMAN PRESCRIPTION DRUG LABEL 1 63539-436 TABLET, FILM COATED 200 mg ORAL NDA 34 sections