tofacitinib indications/contra

Stem definitionDrug idCAS RN
Janus kinase inhibitors, antineoplastics 4713 477600-75-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • tasocitinib
  • xeljanz
  • CP 690550
  • tofacitinib citrate
  • tofacitinib
  • CP-690550
Tofacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs) which modulate intracellular activity including gene expression. Tofacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs.
  • Molecular weight: 312.38
  • Formula: C16H20N6O
  • CLOGP: 1.55
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 1
  • TPSA: 88.91
  • ALOGS: -3.02
  • ROTB: 3

Drug dosage:

DoseUnitRoute
10 mg O

Approvals:

DateAgencyCompanyOrphan
Nov. 6, 2012 FDA PF PRISM CV

FDA Adverse Event Reporting System

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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
Arthralgia 5798.94 42.50 1905 11734 58956 3313264
Musculoskeletal stiffness 4299.43 42.50 1096 12543 12854 3359366
Drug ineffective 4173.88 42.50 1781 11858 114309 3257911
Joint swelling 3914.89 42.50 1061 12578 15996 3356224
Condition aggravated 2592.09 42.50 943 12696 38290 3333930
Fatigue 2414.90 42.50 1197 12442 106043 3266177
Synovitis 2273.96 42.50 452 13187 1393 3370827
Pain 2231.72 42.50 1002 12637 70555 3301665
Headache 2087.15 42.50 1034 12605 90946 3281274
Peripheral swelling 2020.35 42.50 629 13010 15503 3356717
Pain in extremity 2019.52 42.50 838 12801 48374 3323846
Rheumatoid arthritis 1992.96 42.50 618 13021 15020 3357200
Joint range of motion decreased 1719.85 42.50 370 13269 1840 3370380
Herpes zoster 1118.27 42.50 369 13270 10903 3361317
Tenderness 1075.35 42.50 258 13381 2228 3369992
Back pain 1019.12 42.50 482 13157 37523 3334697
Swelling 964.44 42.50 379 13260 18665 3353555
Musculoskeletal pain 942.37 42.50 333 13306 12133 3360087
Diarrhoea 941.63 42.50 648 12991 103700 3268520
Drug effect incomplete 933.25 42.50 295 13344 7555 3364665
Nausea 918.89 42.50 695 12944 128950 3243270
Nasopharyngitis 878.64 42.50 369 13270 21578 3350642
Abdominal discomfort 873.06 42.50 352 13287 18532 3353688
Joint stiffness 845.34 42.50 242 13397 4360 3367860
Sinusitis 804.11 42.50 321 13318 16447 3355773
Cough 741.65 42.50 395 13244 39463 3332757
Weight increased 733.49 42.50 345 13294 26395 3345825
Rash 703.91 42.50 468 13171 70353 3301867
Dry mouth 676.17 42.50 245 13394 9577 3362643
Upper respiratory tract infection 669.00 42.50 242 13397 9413 3362807

Pharmacologic Action:

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SourceCodeDescription
ATC L04AA29 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Selective immunosuppressants
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
CHEBI has role CHEBI:35842 antirheumatic drug
FDA EPC N0000190858 Janus Kinase Inhibitor
FDA MoA N0000190857 Janus Kinase Inhibitors

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Rheumatoid arthritis indication 69896004 DOID:7148

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.27 acidic
pKa2 6.48 Basic
pKa3 0.91 Basic

Orange Book patent data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 5MG BASE XELJANZ PF PRISM CV N203214 Nov. 6, 2012 RX TABLET ORAL 7091208 Dec. 8, 2020 TREATMENT OF RHEUMATOID ARTHRITIS
EQ 11MG BASE XELJANZ XR PFIZER INC N208246 Feb. 23, 2016 RX TABLET, EXTENDED RELEASE ORAL 7091208 Dec. 8, 2020 TREATMENT OF RHEUMATOID ARTHRITIS

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 5MG BASE XELJANZ PF PRISM CV N203214 Nov. 6, 2012 RX TABLET ORAL Dec. 14, 2020 TREATMENT OF ADULT PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS WHO HAVE HAD AN INADEQUATE RESPONSE OR INTOLERANCE TO METHOTREXATE OR OTHER NON-BIOLOGIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS
EQ 11MG BASE XELJANZ XR PFIZER INC N208246 Feb. 23, 2016 RX TABLET, EXTENDED RELEASE ORAL Dec. 14, 2020 TREATMENT OF ADULT PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS WHO HAVE HAD AN INADEQUATE RESPONSE OR INTOLERANCE TO METHOTREXATE OR OTHER NON-BIOLOGIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
JAK2/TYK2 Kinase INHIBITOR IC50 6.64 CHEMBL CHEMBL
JAK1/TYK2 Kinase INHIBITOR IC50 7.46 CHEMBL CHEMBL
JAK2/JAK1 Kinase INHIBITOR IC50 6.39 DRUG LABEL DRUG LABEL
JAK3/JAK1 Kinase INHIBITOR IC50 7.25 DRUG LABEL DRUG LABEL
Tyrosine-protein kinase JAK2 Kinase INHIBITOR Kd 9.24 CHEMBL
Ribosomal protein S6 kinase alpha-6 Kinase Kd 6.27 CHEMBL
Ribosomal protein S6 kinase alpha-1 Kinase Kd 5.85 CHEMBL
JAK1/JAK2/TYK2 Kinase INHIBITOR IC50 7.12 CHEMBL
Tyrosine-protein kinase JAK1 Kinase INHIBITOR Ki 9.17 CHEMBL
G protein-coupled receptor kinase 7 Kinase Kd 5.37 CHEMBL
Serine/threonine-protein kinase N2 Kinase Kd 5.92 CHEMBL
Rho-associated protein kinase 1 Kinase Kd 6.33 CHEMBL
Leucine-rich repeat serine/threonine-protein kinase 2 Kinase Kd 6.26 CHEMBL
BMP-2-inducible protein kinase Kinase Kd 5.15 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 2 Kinase Kd 5.80 CHEMBL
Non-receptor tyrosine-protein kinase TYK2 Kinase INHIBITOR Ki 8.36 CHEMBL
Calcium/calmodulin-dependent protein kinase type 1D Kinase Kd 5.80 CHEMBL
Serine/threonine-protein kinase 3 Kinase Kd 5.37 CHEMBL
Tyrosine-protein kinase JAK3 Kinase INHIBITOR IC50 8.48 WOMBAT-PK
Calcium/calmodulin-dependent protein kinase type II subunit alpha Kinase Kd 5.46 CHEMBL
Serine/threonine-protein kinase ULK3 Kinase Kd 5.19 CHEMBL
Rho-associated protein kinase 2 Kinase Kd 6.38 CHEMBL
Tyrosine-protein kinase Fyn Kinase Kd 5.96 CHEMBL
Protein kinase C delta type Kinase Kd 5.70 CHEMBL
Serine/threonine-protein kinase DCLK3 Kinase Kd 8.35 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase Kd 5.48 CHEMBL
Myotonin-protein kinase Kinase Kd 5.92 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 6.34 CHEMBL
NUAK family SNF1-like kinase 2 Kinase Kd 6.62 CHEMBL
Calcium/calmodulin-dependent protein kinase type II subunit delta Kinase Kd 5.57 CHEMBL
Serine/threonine-protein kinase N1 Kinase Kd 6.77 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 2 Kinase Kd 5.32 CHEMBL
Non-receptor tyrosine-protein kinase TNK1 Kinase Kd 6.92 CHEMBL
Ribosomal protein S6 kinase alpha-2 Kinase Kd 6.22 CHEMBL
Tyrosine-protein kinase ABL1 Kinase Kd 5.66 CHEMBL
Serine/threonine-protein kinase DCLK1 Kinase Kd 5.17 CHEMBL
Calcium/calmodulin-dependent protein kinase type 1 Kinase Kd 5.92 CHEMBL
Serine/threonine-protein kinase PknB Kinase Kd 5.70 CHEMBL
Tyrosine-protein kinase JAK3 Kinase IC50 7.32 CHEMBL
Tyrosine-protein kinase JAK2 Kinase IC50 5.69 CHEMBL

External reference:

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IDSource
5677 IUPHAR_LIGAND_ID
D09783 KEGG_DRUG
4031786 VUID
N0000186059 NUI
C2930696 UMLSCUI
87LA6FU830 UNII
9298 INN_ID
CHEMBL221959 ChEMBL_ID
CHEMBL459769 ChEMBL_ID
C479163 MESH_SUPPLEMENTAL_RECORD_UI
DB08895 DRUGBANK_ID
CHEMBL2103743 ChEMBL_ID
540737-29-9 SECONDARY_CAS_RN
1357536 RXNORM
28976 MMSL
d07925 MMSL
014743 NDDF
4031786 VANDF
N0000186059 NDFRT
704313003 SNOMEDCT_US
704316006 SNOMEDCT_US
9926791 PUBCHEM_CID
CHEBI:71200 CHEBI
MI1 PDB_CHEM_ID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
XELJANZ HUMAN PRESCRIPTION DRUG LABEL 1 0069-0501 TABLET, FILM COATED, EXTENDED RELEASE 11 mg ORAL NDA 20 sections
XELJANZ HUMAN PRESCRIPTION DRUG LABEL 1 0069-1001 TABLET, FILM COATED 5 mg ORAL NDA 20 sections
XELJANZ HUMAN PRESCRIPTION DRUG LABEL 1 63539-012 TABLET, FILM COATED 5 mg ORAL NDA 20 sections
XELJANZ HUMAN PRESCRIPTION DRUG LABEL 1 63539-501 TABLET, EXTENDED RELEASE 11 mg ORAL NDA 20 sections