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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5677 1609392-27-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • deucravacitinib
  • BMS-986165
  • sotyktu
Deucravacitinib is an inhibitor of tyrosine kinase 2 (TYK2). TYK2 is a member of the Janus kinase (JAK) family. Deucravacitinib binds to the regulatory domain of TYK2, stabilizing an inhibitory interaction between the regulatory and the catalytic domains of the enzyme. This results in allosteric inhibition of receptor-mediated activation of TYK2 and its downstream activation of Signal Transducers and Activators of Transcription (STATs) as shown in cell-based assays. JAK kinases, including TYK2, function as pairs of homo- or heterodimers in the JAK-STAT pathways. TYK2 pairs with JAK1 to mediate multiple cytokine pathways and also pairs with JAK2 to transmit signals as shown in cell-based assays. The precise mechanism linking inhibition of TYK2 enzyme to therapeutic effectiveness in the treatment of adults with moderate-to-severe plaque psoriasis is not currently known.
  • Molecular weight: 425.47
  • Formula: C20H22N8O3
  • CLOGP: 1.88
  • LIPINSKI: 1
  • HAC: 11
  • HDO: 3
  • TPSA: 135.95
  • ALOGS: -3.42
  • ROTB: 7
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
6 mg O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.764 High 0.90
caco2-efflux Caco-2 efflux ratio (BA/AB) 5.140 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 45.290 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 1.099 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 30.190 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 47.870 % High 1
herg hERG pIC50 4.385 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.135 uL/min/10^6 cells High 0.90
hlm-clint Human liver microsomal intrinsic clearance 2.965 uL/min/mg protein High 0.90
hppb Human plasma protein binding (% unbound) 19.600 % High 1
kinase-safety-class ACVR2A,ACVR2B,ALK,AURKA,AXL,BLK,BMX,BRAF,CAMK2B,CAMK2D,CDK1,CDK16,CDK2,CDK9,CLK2,CLK4,CSF1R,DDR1,DYRK1A,DYRK1B,EGFR,EIF2AK3,ERBB2,FLT3,GAK,GRK2,GSK3B,IRAK1,IRAK3,ITK,JAK1,KDR,KIT,LCK,MAP3K10,MAP3K11,MAP3K21,MAP3K9,MAP4K1,MAP4K3,MAP4K5,MAPK7,MARK4,MET,NTRK1,PDK1,PDK2,PDK4,PIK3CA,PIK3CD,PIK3CG,PRKCD,PRKDC,SIK2,SIK3,SRC,STK33,TNIK,ULK1 59
kinase-selectivity-class ACVR2B,AURKB,AXL,CAMK2D,CDK1,CDK16,CDK9,CLK2,CLK4,CSF1R,DDR1,DYRK1A,DYRK1B,EGFR,FLT3,GSK3B,IRAK1,IRAK3,JAK1,KIT,MAP3K10,MAP3K11,MAP3K21,MAP4K1,MAP4K3,MAP4K5,MAPK7,MARK4,MET,NTRK1,PDK1,SIK2,SIK3,STK33,SYK,TNIK,TYRO3,ULK1 38
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 32.810 High 1
mh-clint Mouse hepatocyte intrinsic clearance 3.767 High 1
mppb Mouse plasma protein binding (% unbound) 21.130 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 32.137 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 34.260 % High 1
rh-clint Rat hepatocyte intrinsic clearance 1.770 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 72.450 % High 1
rppb Rat plasma protein binding (% unbound) 6.680 % High 0.90
solubility-dd Solubility at pH 7.4 in DMSO 9.226 uM High 1

Approvals:

DateAgencyCompanyOrphan
Sept. 9, 2022 FDA BRISTOL-MYERS SQUIBB
March 24, 2023 EMA BRISTOL-MYERS SQUIBB PHARMA EEIG
Sept. 26, 2022 PMDA BRISTOL-MYERS SQUIBB K.K.

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
Acne 414.38 43.29 93 1222 28414 90598718
Skin burning sensation 209.68 43.29 50 1265 19561 90607571
Pruritus 208.75 43.29 116 1199 541409 90085723
Erythema 199.70 43.29 86 1229 229160 90397972
Mouth ulceration 81.42 43.29 28 1287 39946 90587186
Rash 65.34 43.29 68 1247 796032 89831100
Burning sensation 58.68 43.29 25 1290 63427 90563705
Folliculitis 45.03 43.29 31 1284 204322 90422810

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
Acne 113.28 54.45 29 661 13615 42607030
Skin burning sensation 98.16 54.45 23 667 7464 42613181
Pruritus 94.44 54.45 50 640 188721 42431924
Erythema 84.59 54.45 39 651 108754 42511891
Folliculitis 72.40 54.45 17 673 5541 42615104

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
Acne 388.16 45.78 93 1701 33427 110554078
Skin burning sensation 317.85 45.78 73 1721 21752 110565753
Pruritus 294.40 45.78 155 1639 581405 110006100
Erythema 283.22 45.78 122 1672 291325 110296180
Burning sensation 86.83 45.78 35 1759 69177 110518328
Rash 67.27 45.78 74 1720 820890 109766615
Therapy interrupted 65.23 45.78 26 1768 49796 110537709
Adverse event 56.98 45.78 30 1764 108779 110478726
Folliculitis 52.35 45.78 33 1761 167620 110419885
Product dose omission issue 49.08 45.78 41 1753 321741 110265764
Drug ineffective 47.15 45.78 86 1708 1520454 109067051

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L04AF07 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Janus-associated kinase (JAK) inhibitors
MeSH PA D000092004 Tyrosine Kinase Inhibitors
MeSH PA D003879 Dermatologic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA EPC N0000194043 Tyrosine Kinase 2 Inhibitor
FDA MoA N0000194044 Tyrosine Kinase 2 Inhibitors
CHEBI has role CHEBI:50748 antipsoriatic
CHEBI has role CHEBI:67079 anti-inflammatory agent
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

L04AF Janus-associated kinase (JAK) inhibitors 7 drugs
baricitinibdeuruxolitinibfilgotinibpeficitinibritlecitinibtofacitinibupadacitinib

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

DiseaseRelationSNOMED_IDDOID
Plaque psoriasis indication 200965009
Pustular psoriasis indication 200973000
Erythrodermic psoriasis indication 200977004
Active tuberculosis contraindication 427099000
Severe active infection contraindication




🐶 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
6MG SOTYKTU BRISTOL N214958 Sept. 9, 2022 RX TABLET ORAL 11021475 Nov. 7, 2033 TREATMENT OF MODERATE-TO-SEVERE PLAQUE PSORIASIS IN ADULTS WHO ARE CANDIDATES FOR SYSTEMIC THERAPY OR PHOTOTHERAPY
6MG SOTYKTU BRISTOL N214958 Sept. 9, 2022 RX TABLET ORAL RE47929 Nov. 7, 2033 TREATMENT OF ACTIVE PSORIATIC ARTHRITIS IN ADULTS
6MG SOTYKTU BRISTOL N214958 Sept. 9, 2022 RX TABLET ORAL RE47929 Nov. 7, 2033 TREATMENT OF MODERATE-TO-SEVERE PLAQUE PSORIASIS IN ADULTS WHO ARE CANDIDATES FOR SYSTEMIC THERAPY OR PHOTOTHERAPY
6MG SOTYKTU BRISTOL N214958 Sept. 9, 2022 RX TABLET ORAL 12521390 Feb. 11, 2043 TREATMENT OF ADULTS WITH ACTIVE PSORIATIC ARTHRITIS
6MG SOTYKTU BRISTOL N214958 Sept. 9, 2022 RX TABLET ORAL 12521390 Feb. 11, 2043 TREATMENT OF MODERATE-TO-SEVERE PLAQUE PSORIASIS IN ADULTS WHO ARE CANDIDATES FOR SYSTEMIC THERAPY OR PHOTOTHERAPY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
6MG SOTYKTU BRISTOL N214958 Sept. 9, 2022 RX TABLET ORAL Sept. 9, 2027 NEW CHEMICAL ENTITY
6MG SOTYKTU BRISTOL N214958 Sept. 9, 2022 RX TABLET ORAL March 6, 2029 TREATMENT OF ACTIVE PSORIATIC ARTHRITIS IN ADULTS

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Non-receptor tyrosine-protein kinase TYK2 Kinase INHIBITOR IC50 9.70 SCIENTIFIC LITERATURE DRUG LABEL
Tyrosine-protein kinase JAK2 Kinase Kd 8 CHEMBL
Signal transducer and activator of transcription 3 Transcription factor IC50 7.05 CHEMBL
Signal transducer and activator of transcription 1-alpha/beta Transcription factor IC50 7.47 CHEMBL
Tyrosine-protein kinase JAK3 Kinase IC50 8.52 CHEMBL
Tyrosine-protein kinase JAK1 Kinase INHIBITOR IC50 9 SCIENTIFIC LITERATURE
Bone morphogenetic protein receptor type-2 Kinase INHIBITOR IC50 6.71 SCIENTIFIC LITERATURE
Non-receptor tyrosine-protein kinase TYK2 Kinase IC50 7 CHEMBL

External reference:

IDSource
CHEBI:757668 CHEBI
CHEMBL4435170 ChEMBL_ID
C000628674 MESH_SUPPLEMENTAL_RECORD_UI
10432 IUPHAR_LIGAND_ID
DB16650 DRUGBANK_ID
1025321000122103 SNOMEDCT_US
4041706 VANDF
C5420928 UMLSCUI
11342 INN_ID
D11817 KEGG_DRUG
134821691 PUBCHEM_CID
361718 MMSL
40933 MMSL
d09921 MMSL
019177 NDDF
N0A21N6RAU UNII
2612087 RXNORM

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
SOTYKTU HUMAN PRESCRIPTION DRUG LABEL 1 0003-0895 TABLET, FILM COATED 6 mg ORAL NDA 29 sections