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 613.53 41.07 155 1020 16940 2339970
Diarrhoea 481.33 41.07 186 989 83378 2273532
Renal cancer 342.05 41.07 56 1119 628 2356282
Death 265.57 41.07 122 1053 81346 2275564
Hypertension 239.99 41.07 84 1091 27277 2329633
Neoplasm progression 229.56 41.07 55 1120 4613 2352297
Metastatic renal cell carcinoma 223.13 41.07 34 1141 227 2356683
Decreased appetite 209.12 41.07 77 1098 28814 2328096
Fatigue 199.80 41.07 102 1073 84771 2272139
Renal cell carcinoma 174.00 41.07 32 1143 725 2356185
Dysphonia 132.71 41.07 38 1137 6326 2350584
Weight decreased 125.13 41.07 53 1122 28318 2328592
Dehydration 116.34 41.07 47 1128 22248 2334662
Nausea 114.78 41.07 79 1096 112110 2244800
Palmar-plantar erythrodysaesthesia syndrome 114.67 41.07 31 1144 4170 2352740
Hypothyroidism 108.22 41.07 30 1145 4427 2352483
Stomatitis 100.80 41.07 34 1141 9676 2347234
Blood pressure increased 99.64 41.07 39 1136 16947 2339963
Asthenia 94.03 41.07 51 1124 46875 2310035
Vomiting 69.39 41.07 49 1126 71553 2285357
Proteinuria 59.20 41.07 17 1158 2833 2354077
Posterior reversible encephalopathy syndrome 56.95 41.07 16 1159 2464 2354446
Constipation 53.06 41.07 27 1148 21602 2335308
Renal cancer metastatic 47.75 41.07 8 1167 102 2356808
General physical health deterioration 44.69 41.07 21 1154 14118 2342792

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 1855.50 44.22 499 2446 16764 1727072
Diarrhoea 942.96 44.22 399 2546 53453 1690383
Renal cancer 856.43 44.22 162 2783 929 1742907
Death 680.34 44.22 372 2573 87071 1656765
Dysphonia 650.36 44.22 159 2786 3396 1740440
Hypertension 558.89 44.22 208 2737 19240 1724596
Metastatic renal cell carcinoma 524.54 44.22 98 2847 513 1743323
Fatigue 501.46 44.22 255 2690 50526 1693310
Renal cell carcinoma 491.40 44.22 108 2837 1400 1742436
Neoplasm progression 451.89 44.22 117 2828 3150 1740686
Decreased appetite 385.44 44.22 169 2776 23702 1720134
Blood pressure increased 235.83 44.22 95 2850 10658 1733178
Nausea 212.70 44.22 148 2797 51048 1692788
Weight decreased 206.98 44.22 109 2836 22644 1721192
Palmar-plantar erythrodysaesthesia syndrome 199.77 44.22 63 2882 3444 1740392
Neoplasm malignant 178.71 44.22 61 2884 4278 1739558
Stomatitis 176.80 44.22 64 2881 5340 1738496
Asthenia 174.17 44.22 113 2832 34557 1709279
Hypothyroidism 149.92 44.22 47 2898 2513 1741323
Constipation 145.06 44.22 75 2870 14925 1728911
Dehydration 133.56 44.22 75 2870 17583 1726253
Proteinuria 117.07 44.22 40 2905 2804 1741032
Malaise 102.66 44.22 77 2868 29488 1714348
Pain in extremity 99.27 44.22 63 2882 18409 1725427
Headache 96.59 44.22 79 2866 34297 1709539
Renal impairment 94.86 44.22 53 2892 12261 1731575
Dyspnoea 93.67 44.22 93 2852 51966 1691870
Vomiting 87.12 44.22 78 2867 38237 1705599
Oral pain 86.78 44.22 27 2918 1403 1742433
Renal cancer metastatic 85.19 44.22 18 2927 188 1743648
Second primary malignancy 72.76 44.22 22 2923 1037 1742799
Acute kidney injury 63.71 44.22 63 2882 34881 1708955
Aphonia 63.48 44.22 17 2928 514 1743322
Dysgeusia 62.72 44.22 30 2915 5019 1738817
Arthralgia 59.72 44.22 51 2894 23393 1720443
Blood thyroid stimulating hormone increased 55.85 44.22 16 2929 623 1743213
Nephrotic syndrome 54.67 44.22 19 2926 1397 1742439
Blood creatinine increased 54.28 44.22 39 2906 13907 1729929
Glossodynia 54.08 44.22 16 2929 699 1743137
Posterior reversible encephalopathy syndrome 53.91 44.22 19 2926 1456 1742380
Pneumothorax 52.54 44.22 22 2923 2690 1741146
General physical health deterioration 49.48 44.22 36 2909 13082 1730754
Dry mouth 47.83 44.22 23 2922 3890 1739946
Cough 47.30 44.22 41 2904 19156 1724680
Blister 46.85 44.22 23 2922 4069 1739767
Dry skin 45.92 44.22 22 2923 3690 1740146
Malignant urinary tract neoplasm 45.76 44.22 8 2937 26 1743810

Pharmacologic Action:

SourceCodeDescription
ATC L01XE17 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Protein kinase inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000020000 Receptor Tyrosine Kinase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase 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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
1MG INLYTA PF PRISM CV N202324 Jan. 27, 2012 RX TABLET ORAL 7141581 June 30, 2020 TREATMENT OF RENAL CELL CARCINOMA
5MG INLYTA PF PRISM CV N202324 Jan. 27, 2012 RX TABLET ORAL 7141581 June 30, 2020 TREATMENT OF RENAL CELL CARCINOMA

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
D000077784 MESH_DESCRIPTOR_UI
4031332 VUID
N0000184323 NUI
C1700874 UMLSCUI
D03218 KEGG_DRUG
429507005 SNOMEDCT_US
427882000 SNOMEDCT_US
1242999 RXNORM
014143 NDDF
28294 MMSL
d07823 MMSL
4031332 VANDF
C9LVQ0YUXG UNII
8720 INN_ID
6450551 PUBCHEM_CID
CHEBI:66910 CHEBI
AXI PDB_CHEM_ID
DB06626 DRUGBANK_ID
5659 IUPHAR_LIGAND_ID
CHEMBL1289926 ChEMBL_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
INLYTA HUMAN PRESCRIPTION DRUG LABEL 1 0069-0145 TABLET, FILM COATED 1 mg ORAL NDA 19 sections
INLYTA HUMAN PRESCRIPTION DRUG LABEL 1 0069-0151 TABLET, FILM COATED 5 mg ORAL NDA 19 sections
INLYTA HUMAN PRESCRIPTION DRUG LABEL 1 63539-026 TABLET, FILM COATED 1 mg ORAL NDA 19 sections
INLYTA HUMAN PRESCRIPTION DRUG LABEL 1 63539-044 TABLET, FILM COATED 5 mg ORAL NDA 19 sections