axitinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 4225 319460-85-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • axitinib
  • inlyta
  • AG 013736
  • AG-013736
A benzamide and indazole derivative that acts as a TYROSINE KINASE inhibitor of the VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR. It is used in the treatment of advanced RENAL CELL CARCINOMA.
  • Molecular weight: 386.47
  • Formula: C22H18N4OS
  • CLOGP: 3.33
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 2
  • TPSA: 70.67
  • ALOGS: -5.85
  • ROTB: 5

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ
CL (Clearance) 5 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.00 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 4.30 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Jan. 27, 2012 FDA PFIZER

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
Disease progression 342.66 27.02 168 4235 91132 46590527
Neoplasm progression 282.99 27.02 103 4300 26580 46655079
Renal cancer 248.25 27.02 58 4345 3110 46678549
Diarrhoea 214.04 27.02 261 4142 559341 46122318
Metastatic renal cell carcinoma 173.63 27.02 35 4368 928 46680731
Death 167.10 27.02 180 4223 335368 46346291
Hypertension 143.29 27.02 130 4273 196226 46485433
Renal cell carcinoma 119.06 27.02 33 4370 3505 46678154
Palmar-plantar erythrodysaesthesia syndrome 105.24 27.02 47 4356 20404 46661255
Decreased appetite 101.25 27.02 107 4296 193729 46487930
Dysphonia 93.10 27.02 53 4350 38361 46643298
Hypothyroidism 77.97 27.02 44 4359 31294 46650365
Stomatitis 71.83 27.02 56 4347 68241 46613418
Blood pressure increased 67.89 27.02 71 4332 126595 46555064
Fatigue 46.71 27.02 144 4259 608553 46073106
Posterior reversible encephalopathy syndrome 39.64 27.02 22 4381 15119 46666540
Dehydration 38.27 27.02 60 4343 159480 46522179
Weight decreased 38.27 27.02 70 4333 210779 46470880
Renal cancer metastatic 35.83 27.02 8 4395 348 46681311
Oligodipsia 32.56 27.02 5 4398 24 46681635
Oral pain 31.96 27.02 23 4380 24774 46656885
Proteinuria 27.60 27.02 18 4385 16535 46665124
Drug ineffective 27.46 27.02 15 4388 677823 46003836

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
Disease progression 1060.18 20.46 538 10637 79336 29861967
Renal cancer 650.37 20.46 173 11002 3867 29937436
Neoplasm progression 630.76 20.46 241 10934 17782 29923521
Dysphonia 530.73 20.46 216 10959 18816 29922487
Diarrhoea 413.16 20.46 559 10616 333544 29607759
Metastatic renal cell carcinoma 378.57 20.46 102 11073 2390 29938913
Renal cell carcinoma 345.30 20.46 115 11060 5651 29935652
Death 335.00 20.46 525 10650 356758 29584545
Hypertension 305.99 20.46 295 10880 121059 29820244
Palmar-plantar erythrodysaesthesia syndrome 230.63 20.46 112 11063 14758 29926545
Fatigue 181.89 20.46 380 10795 320293 29621010
Decreased appetite 142.62 20.46 223 10952 149687 29791616
Blood pressure increased 122.02 20.46 142 11033 71786 29869517
Hypothyroidism 102.77 20.46 66 11109 14897 29926406
Neoplasm malignant 96.95 20.46 68 11107 17746 29923557
Aphonia 93.09 20.46 37 11138 3007 29938296
Stomatitis 92.23 20.46 90 11085 37189 29904114
Drug ineffective 76.36 20.46 17 11158 340370 29600933
Renal cancer metastatic 71.42 20.46 20 11155 541 29940762
Oral pain 60.66 20.46 40 11135 9429 29931874
Second primary malignancy 53.68 20.46 32 11143 6324 29934979
Weight decreased 51.71 20.46 148 11027 150773 29790530
Proteinuria 51.59 20.46 45 11130 16100 29925203
Glossodynia 48.12 20.46 24 11151 3337 29937966
Malignant urinary tract neoplasm 47.83 20.46 8 11167 12 29941291
Toxicity to various agents 43.55 20.46 7 11168 177176 29764127
Neutropenia 31.74 20.46 5 11170 128535 29812768
Blood thyroid stimulating hormone increased 31.16 20.46 17 11158 2839 29938464
Thyroid disorder 29.18 20.46 16 11159 2698 29938605
Therapy interrupted 28.68 20.46 19 11156 4510 29936793
Nausea 28.10 20.46 198 10977 296759 29644544
Oral discomfort 24.57 20.46 14 11161 2542 29938761
Febrile neutropenia 24.49 20.46 5 11170 106688 29834615
Blister 24.17 20.46 34 11141 20649 29920654
Posterior reversible encephalopathy syndrome 23.35 20.46 22 11153 8685 29932618
Constipation 22.89 20.46 93 11082 112813 29828490
Pain in extremity 22.52 20.46 91 11084 110130 29831173
Renal cell carcinoma stage IV 22.07 20.46 5 11170 55 29941248
Dry skin 22.04 20.46 34 11141 22420 29918883
Nephrotic syndrome 21.60 20.46 19 11156 6866 29934437
Drug interaction 21.21 20.46 26 11149 199542 29741761
Dysgeusia 20.85 20.46 35 11140 24766 29916537
Clear cell renal cell carcinoma 20.64 20.46 9 11166 922 29940381
Dehydration 20.64 20.46 96 11079 123443 29817860

Pharmacologic Action:

SourceCodeDescription
ATC L01EK01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors
FDA MoA N0000020000 Receptor Tyrosine Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:38637 tyrosine kinase inhibitors
CHEBI has role CHEBI:65207 vegfr inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Renal cell carcinoma indication 702391001 DOID:4450

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.57 acidic
pKa2 12.18 acidic
pKa3 4.85 Basic
pKa4 1.98 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Vascular endothelial growth factor receptor 3 Kinase INHIBITOR Kd 6.77 CHEMBL CHEMBL
Vascular endothelial growth factor receptor 1 Kinase INHIBITOR Kd 8.24 CHEMBL CHEMBL
Vascular endothelial growth factor receptor 2 Kinase INHIBITOR Kd 8.23 CHEMBL CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase Kd 7.51 CHEMBL
Cyclin-dependent kinase-like 2 Kinase Kd 6.28 CHEMBL
Epidermal growth factor receptor Kinase Kd 5.64 CHEMBL
Fibroblast growth factor receptor 3 Kinase Kd 6.68 CHEMBL
SRSF protein kinase 1 Kinase Kd 5.74 CHEMBL
Platelet-derived growth factor receptor alpha Kinase Kd 9.29 CHEMBL
Serine/threonine-protein kinase RIO3 Kinase Kd 6 CHEMBL
Hepatocyte growth factor receptor Kinase Kd 6.09 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 5 CHEMBL
Tyrosine-protein kinase JAK2 Kinase Kd 5.48 CHEMBL
Cyclin-G-associated kinase Kinase Kd 5.57 CHEMBL
Aurora kinase A Kinase Kd 7.14 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5 Kinase Kd 6.85 CHEMBL
Tyrosine-protein kinase ITK/TSK Kinase Kd 5.92 CHEMBL
Mitogen-activated protein kinase kinase kinase MLT Kinase Kd 5.59 CHEMBL
Interferon-induced, double-stranded RNA-activated protein kinase Kinase Kd 5.13 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 1 Kinase Kd 6.48 CHEMBL
Tyrosine-protein kinase Fgr Kinase Kd 5.74 CHEMBL
Dual specificity protein kinase TTK Kinase Kd 5.41 CHEMBL
Serine/threonine-protein kinase 10 Kinase Kd 5.92 CHEMBL
Serine/threonine-protein kinase 16 Kinase Kd 6.43 CHEMBL
Serine/threonine-protein kinase PLK4 Kinase Ki 8.38 CHEMBL
AP2-associated protein kinase 1 Kinase Kd 5.92 CHEMBL
Tyrosine-protein kinase JAK3 Kinase Kd 5.51 CHEMBL
Casein kinase II subunit alpha' Kinase Kd 5.55 CHEMBL
Tyrosine-protein kinase Yes Kinase Kd 5.57 CHEMBL
Serine/threonine-protein kinase N2 Kinase Kd 5.57 CHEMBL
Tyrosine-protein kinase CSK Kinase Kd 5.96 CHEMBL
Aurora kinase C Kinase Kd 8.89 CHEMBL
High affinity nerve growth factor receptor Kinase Kd 5.74 CHEMBL
Platelet-derived growth factor receptor beta Kinase Kd 9.24 CHEMBL
Fibroblast growth factor receptor 1 Kinase Kd 6.42 CHEMBL
Fibroblast growth factor receptor 2 Kinase Kd 6.96 CHEMBL
Myosin-IIIa Kinase Kd 5.72 CHEMBL
Ankyrin repeat and protein kinase domain-containing protein 1 Kinase Kd 5.44 CHEMBL
Mitogen-activated protein kinase kinase kinase 4 Kinase Kd 5.25 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 5 Kinase Kd 6.26 CHEMBL
Misshapen-like kinase 1 Kinase Kd 6.25 CHEMBL
Leucine-rich repeat serine/threonine-protein kinase 2 Kinase Kd 6.04 CHEMBL
Mast/stem cell growth factor receptor Kit Kinase Kd 9.31 CHEMBL
BMP-2-inducible protein kinase Kinase Kd 6 CHEMBL
TRAF2 and NCK-interacting protein kinase Kinase Kd 6.74 CHEMBL
Calcium/calmodulin-dependent protein kinase kinase 2 Kinase Kd 5.82 CHEMBL
Aurora kinase B Kinase Kd 7.96 CHEMBL
STE20-like serine/threonine-protein kinase Kinase Kd 6 CHEMBL
Bone morphogenetic protein receptor type-1B Kinase Kd 5.54 CHEMBL
Non-receptor tyrosine-protein kinase TYK2 Kinase Kd 5.44 CHEMBL
Interleukin-1 receptor-associated kinase 1 Kinase Kd 5.51 CHEMBL
Serine/threonine-protein kinase 4 Kinase Kd 5.85 CHEMBL
Calcium/calmodulin-dependent protein kinase kinase 1 Kinase Kd 5.85 CHEMBL
Serine/threonine-protein kinase 3 Kinase Kd 5.66 CHEMBL
Serine/threonine-protein kinase ULK2 Kinase Kd 5 CHEMBL
Activated CDC42 kinase 1 Kinase Kd 5.22 CHEMBL
Cyclin-dependent kinase 16 Kinase Kd 5.28 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 3 Kinase Kd 5.92 CHEMBL
Dual specificity testis-specific protein kinase 1 Kinase Kd 5.37 CHEMBL
Serine/threonine-protein kinase MRCK beta Kinase Kd 5.32 CHEMBL
G protein-coupled receptor kinase 4 Kinase Kd 5.64 CHEMBL
Serine/threonine-protein kinase ULK3 Kinase Kd 6.17 CHEMBL
Abelson tyrosine-protein kinase 2 Kinase Kd 7.15 CHEMBL
Activin receptor type-2B Kinase Kd 5.28 CHEMBL
Tyrosine-protein kinase Blk Kinase Kd 5.51 CHEMBL
Angiopoietin-1 receptor Kinase Kd 6.51 CHEMBL
Proto-oncogene tyrosine-protein kinase ROS Kinase Kd 5.49 CHEMBL
Ephrin type-B receptor 6 Kinase Kd 6.44 CHEMBL
Mitogen-activated protein kinase 8 Kinase Kd 5.41 CHEMBL
Macrophage colony-stimulating factor 1 receptor Kinase Kd 7.68 CHEMBL
Hormonally up-regulated neu tumor-associated kinase Kinase Kd 5.82 CHEMBL
Discoidin domain-containing receptor 2 Kinase Kd 5.28 CHEMBL
Tyrosine-protein kinase receptor Tie-1 Kinase Kd 7.01 CHEMBL
Serine/threonine-protein kinase PAK 4 Kinase Kd 5.35 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase Kd 7 CHEMBL
Epithelial discoidin domain-containing receptor 1 Kinase Kd 6.47 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 4 Kinase Kd 6.46 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 5.57 CHEMBL
Myosin light chain kinase 2, skeletal/cardiac muscle Kinase Kd 5.89 CHEMBL
Mitogen-activated protein kinase kinase kinase 9 Kinase Kd 5.52 CHEMBL
Mitogen-activated protein kinase kinase kinase 19 Kinase Kd 6.57 CHEMBL
Tyrosine-protein kinase receptor UFO Kinase Kd 6.38 CHEMBL
NUAK family SNF1-like kinase 2 Kinase Kd 5.89 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 2 Kinase Kd 5.59 CHEMBL
SRSF protein kinase 3 Kinase Kd 5.64 CHEMBL
Tyrosine-protein kinase TXK Kinase Kd 5.62 CHEMBL
Mitogen-activated protein kinase kinase kinase 12 Kinase Kd 5.77 CHEMBL
Myosin light chain kinase 3 Kinase Kd 5.77 CHEMBL
Receptor-interacting serine/threonine-protein kinase 1 Kinase Kd 5.60 CHEMBL
Mitogen-activated protein kinase kinase kinase 3 Kinase Kd 5.55 CHEMBL
Serine/threonine-protein kinase RIO1 Kinase Kd 5.92 CHEMBL
Receptor-interacting serine/threonine-protein kinase 4 Kinase Kd 5.85 CHEMBL
Serine/threonine-protein kinase SIK1 Kinase Kd 5.68 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 2 Kinase Kd 5.89 CHEMBL
Tyrosine-protein kinase Mer Kinase Kd 5.49 CHEMBL
Mitogen-activated protein kinase 10 Kinase Kd 5.96 CHEMBL
Non-receptor tyrosine-protein kinase TNK1 Kinase Kd 6.80 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 1 Kinase Kd 5.57 CHEMBL
Tyrosine-protein kinase ABL1 Kinase Kd 8.82 CHEMBL

External reference:

IDSource
C9LVQ0YUXG UNII
4031332 VUID
N0000184323 NUI
D03218 KEGG_DRUG
4031332 VANDF
C1328149 UMLSCUI
CHEBI:66910 CHEBI
AXI PDB_CHEM_ID
CHEMBL1289926 ChEMBL_ID
6450551 PUBCHEM_CID
DB06626 DRUGBANK_ID
D000077784 MESH_DESCRIPTOR_UI
8720 INN_ID
5659 IUPHAR_LIGAND_ID
1242999 RXNORM
187097 MMSL
28294 MMSL
d07823 MMSL
014143 NDDF
427882000 SNOMEDCT_US
429507005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
INLYTA HUMAN PRESCRIPTION DRUG LABEL 1 0069-0145 TABLET, FILM COATED 1 mg ORAL NDA 32 sections
INLYTA HUMAN PRESCRIPTION DRUG LABEL 1 0069-0151 TABLET, FILM COATED 5 mg ORAL NDA 32 sections
INLYTA HUMAN PRESCRIPTION DRUG LABEL 1 63539-026 TABLET, FILM COATED 1 mg ORAL NDA 29 sections
INLYTA HUMAN PRESCRIPTION DRUG LABEL 1 63539-044 TABLET, FILM COATED 5 mg ORAL NDA 29 sections