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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 1282 184475-35-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ZD1839
  • gefitinib
  • iressa
  • ZD 1839
Gefitinib reversibly inhibits the kinase activity of wild-type and certain activating mutations of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor, thereby inhibiting further downstream signalling and blocking EGFR-dependent proliferation.
  • Molecular weight: 446.91
  • Formula: C22H24ClFN4O3
  • CLOGP: 5.45
  • LIPINSKI: 1
  • HAC: 7
  • HDO: 1
  • TPSA: 68.74
  • ALOGS: -4.22
  • ROTB: 8

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.00 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 2 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 8 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 60 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 23 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 12 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.09 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 34 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
May 5, 2003 FDA

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
Malignant neoplasm progression 1087.01 42.12 255 1746 11873 2344211
Diarrhoea 499.22 42.12 224 1777 83340 2272744
Interstitial lung disease 474.76 42.12 121 1880 7691 2348393
Drug resistance 383.82 42.12 83 1918 2541 2353543
Hepatic function abnormal 382.66 42.12 97 1904 5995 2350089
Liver disorder 324.36 42.12 86 1915 6328 2349756
Disease progression 283.80 42.12 97 1904 16998 2339086
Lung disorder 260.91 42.12 72 1929 6140 2349944
Metastases to central nervous system 236.96 42.12 54 1947 2094 2353990
Rash 205.99 42.12 111 1890 59447 2296637
Pneumonia 137.55 42.12 80 1921 49216 2306868
Pleural effusion 128.38 42.12 49 1952 11619 2344465
Vomiting 126.56 42.12 87 1914 71515 2284569
Pyrexia 120.96 42.12 76 1925 53632 2302452
Acquired gene mutation 120.89 42.12 20 1981 130 2355954
Paronychia 114.26 42.12 25 1976 797 2355287
Decreased appetite 111.00 42.12 58 1943 28833 2327251
Dehydration 109.86 42.12 53 1948 22242 2333842
Dermatitis acneiform 109.09 42.12 24 1977 785 2355299
Alanine aminotransferase increased 96.21 42.12 42 1959 13990 2342094
Nausea 93.99 42.12 88 1913 112101 2243983
Dyspnoea 90.46 42.12 74 1927 78659 2277425
EGFR gene mutation 90.46 42.12 13 1988 26 2356058
Metastases to meninges 89.54 42.12 18 1983 376 2355708
Malignant transformation 88.60 42.12 13 1988 32 2356052
Dry skin 84.23 42.12 31 1970 6621 2349463
Aspartate aminotransferase increased 80.78 42.12 36 1965 12576 2343508
Respiratory failure 78.36 42.12 36 1965 13492 2342592
Stomatitis 72.86 42.12 31 1970 9679 2346405
Metastases to bone 71.16 42.12 21 1980 2248 2353836
Skin disorder 69.36 42.12 23 1978 3608 2352476
Skin toxicity 66.62 42.12 16 1985 774 2355310
Anaemia 62.82 42.12 43 1958 34749 2321335
Pneumothorax 62.14 42.12 19 1982 2293 2353791
Metastases to liver 61.69 42.12 20 1981 2921 2353163
Asthenia 57.68 42.12 46 1955 46880 2309204
Pneumonitis 55.47 42.12 20 1981 4019 2352065
Pulmonary embolism 54.55 42.12 31 1970 18052 2338032
Lymphangiosis carcinomatosa 54.42 42.12 11 1990 236 2355848
Metastases to lung 54.18 42.12 16 1985 1715 2354369
Small cell lung cancer 53.00 42.12 11 1990 270 2355814
Hypoxia 50.42 42.12 21 1980 6206 2349878
Acne 48.43 42.12 17 1984 3159 2352925
Nail disorder 46.75 42.12 13 1988 1123 2354961
Skin ulcer 44.37 42.12 17 1984 4042 2352042

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
Interstitial lung disease 560.13 41.42 150 1344 9546 1735741
Malignant neoplasm progression 473.31 41.42 143 1351 14015 1731272
Lung disorder 292.87 41.42 79 1415 5040 1740247
Diarrhoea 231.80 41.42 124 1370 53728 1691559
Disease progression 202.01 41.42 80 1414 17183 1728104
Rash 200.05 41.42 101 1393 38592 1706695
Pneumonia 194.40 41.42 105 1389 46077 1699210
Drug resistance 175.65 41.42 48 1446 3182 1742105
Dehydration 126.80 41.42 58 1436 17600 1727687
Hepatic function abnormal 119.42 41.42 43 1451 7031 1738256
Nausea 114.86 41.42 78 1416 51118 1694169
Vomiting 114.58 41.42 70 1424 38245 1707042
Respiratory failure 105.13 41.42 48 1446 14457 1730830
Decreased appetite 104.49 41.42 56 1438 23815 1721472
Metastases to central nervous system 102.95 41.42 27 1467 1518 1743769
Pyrexia 95.20 41.42 67 1427 46333 1698954
Dermatitis acneiform 92.78 41.42 23 1471 1029 1744258
Liver disorder 86.63 41.42 32 1462 5604 1739683
Dyspnoea 81.66 41.42 64 1430 51995 1693292
Acquired gene mutation 73.02 41.42 14 1480 181 1745106
Pleural effusion 71.78 41.42 34 1460 11076 1734211
Metastases to bone 63.57 41.42 19 1475 1719 1743568
Lymphangiosis carcinomatosa 58.86 41.42 12 1482 216 1745071
Hypoxia 56.90 41.42 24 1470 5939 1739348
Pneumonitis 55.61 41.42 21 1473 3894 1741393
Pulmonary embolism 49.65 41.42 28 1466 13031 1732256
Metastases to lung 48.51 41.42 15 1479 1520 1743767
Anaemia 47.64 41.42 37 1457 29420 1715867
Hypophagia 46.93 41.42 18 1476 3479 1741808
Haemoptysis 44.42 41.42 19 1475 4857 1740430
Lung infiltration 43.48 41.42 15 1479 2144 1743143
Cerebral infarction 43.21 41.42 19 1475 5190 1740097
Alanine aminotransferase increased 43.10 41.42 25 1469 12253 1733034
Paronychia 42.78 41.42 11 1483 569 1744718
Metastases to pleura 41.67 41.42 8 1486 104 1745183

Pharmacologic Action:

SourceCodeDescription
ATC L01XE02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Protein kinase inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
FDA EPC N0000175605 Kinase Inhibitor

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer indication 254637007 DOID:3908
Non-small cell lung cancer, positive for epidermal growth factor receptor expression indication 426964009
Fibrosis of lung contraindication 51615001 DOID:3770
Acute nephropathy contraindication 58574008
Interstitial pneumonia contraindication 64667001
Disease of liver contraindication 235856003 DOID:409
Pregnancy, function contraindication 289908002
Breastfeeding (mother) contraindication 413712001
Non-small cell lung cancer, negative for epidermal growth factor receptor expression contraindication 427038005

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 7.65 Basic
pKa2 5.8 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
250MG IRESSA ASTRAZENECA PHARMS N206995 July 13, 2015 RX TABLET ORAL July 13, 2022 FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS HAVE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETIONS OR EXON 21 (L858R) SUBSTITUTION MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Epidermal growth factor receptor Kinase INHIBITOR Ki 9.40 CHEMBL CHEMBL
Mitogen-activated protein kinase 10 Kinase Kd 5.64 CHEMBL
Tyrosine-protein kinase ABL1 Kinase Kd 6.64 CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase Kd 6 CHEMBL
Mitogen-activated protein kinase 9 Kinase Kd 5.85 CHEMBL
Vascular endothelial growth factor receptor 2 Kinase IC50 5.72 CHEMBL
Hepatocyte growth factor receptor Kinase Kd 5.46 CHEMBL
Casein kinase I isoform epsilon Kinase Kd 6.37 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 6.28 CHEMBL
Ephrin type-B receptor 4 Kinase Kd 5.60 CHEMBL
Cyclin-G-associated kinase Kinase Kd 8.15 CHEMBL
Serine/threonine-protein kinase SBK1 Kinase Kd 6.25 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5 Kinase Kd 6.22 CHEMBL
Casein kinase I isoform delta Kinase Kd 5.49 CHEMBL
Serine/threonine-protein kinase pim-3 Kinase Kd 5.24 CHEMBL
Serine/threonine-protein kinase D1 Kinase Kd 5.46 CHEMBL
Ephrin type-A receptor 1 Kinase Kd 5.40 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 1 Kinase Kd 6.54 CHEMBL
Tyrosine-protein kinase Fgr Kinase Kd 5.59 CHEMBL
Tyrosine-protein kinase FRK Kinase Kd 5.70 CHEMBL
Ephrin type-A receptor 8 Kinase Kd 5.74 CHEMBL
Ephrin type-A receptor 3 Kinase Kd 5.26 CHEMBL
Serine/threonine-protein kinase 10 Kinase Kd 6.33 CHEMBL
Serine/threonine-protein kinase 17B Kinase Kd 5.42 CHEMBL
Receptor tyrosine-protein kinase erbB-2 Kinase Kd 5.96 CHEMBL
Tyrosine-protein kinase HCK Kinase Kd 5.36 CHEMBL
Phosphorylase b kinase gamma catalytic chain, liver/testis isoform Kinase Kd 5.57 CHEMBL
Citron Rho-interacting kinase Kinase Kd 5.89 CHEMBL
Homeodomain-interacting protein kinase 4 Kinase Kd 6.51 CHEMBL
Misshapen-like kinase 1 Kinase Kd 5.74 CHEMBL
Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma Kinase Kd 5.12 CHEMBL
Interleukin-1 receptor-associated kinase 4 Kinase Kd 6.27 CHEMBL
Serine/threonine-protein kinase 36 Kinase Kd 5.24 CHEMBL
Mast/stem cell growth factor receptor Kit Kinase Kd 5.74 CHEMBL
Receptor tyrosine-protein kinase erbB-4 Kinase Kd 6.39 CHEMBL
Serine/threonine-protein kinase 17A Kinase Kd 5.70 CHEMBL
Ephrin type-A receptor 6 Kinase Kd 6.23 CHEMBL
TRAF2 and NCK-interacting protein kinase Kinase Kd 5.16 CHEMBL
Ribosomal protein S6 kinase alpha-4 Kinase Kd 5.92 CHEMBL
STE20-like serine/threonine-protein kinase Kinase Kd 6.04 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 2 Kinase Kd 6.44 CHEMBL
Interleukin-1 receptor-associated kinase 1 Kinase Kd 7.16 CHEMBL
Tyrosine-protein kinase Lyn Kinase Kd 6 CHEMBL
Ephrin type-A receptor 5 Kinase Kd 5.82 CHEMBL
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform Kinase Kd 5.43 CHEMBL
Ephrin type-B receptor 1 Kinase Kd 5.89 CHEMBL
Interleukin-1 receptor-associated kinase 3 Kinase Kd 5.82 CHEMBL
Mitogen-activated protein kinase kinase kinase 2 Kinase Kd 5.48 CHEMBL
Abelson tyrosine-protein kinase 2 Kinase Kd 5.80 CHEMBL
Tyrosine-protein kinase Blk Kinase Kd 5.92 CHEMBL
Receptor tyrosine-protein kinase erbB-3 Kinase Kd 6.10 CHEMBL
Ephrin type-B receptor 6 Kinase Kd 5.49 CHEMBL
Serine/threonine-protein kinase SIK2 Kinase Kd 5.68 CHEMBL
Cyclin-dependent kinase 7 Kinase Kd 6.21 CHEMBL
Mitogen-activated protein kinase 4 Kinase Kd 5.51 CHEMBL
Mitogen-activated protein kinase 6 Kinase Kd 5.80 CHEMBL
Death-associated protein kinase 3 Kinase Kd 5.24 CHEMBL
Serine/threonine-protein kinase DCLK3 Kinase Kd 5.54 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase IC50 5.77 CHEMBL
Myotonin-protein kinase Kinase Kd 5.16 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 6.20 CHEMBL
Myosin light chain kinase 2, skeletal/cardiac muscle Kinase Kd 5.72 CHEMBL
Leukocyte tyrosine kinase receptor Kinase Kd 5.26 CHEMBL
Mitogen-activated protein kinase kinase kinase 19 Kinase Kd 6.62 CHEMBL
Tyrosine-protein kinase receptor UFO Kinase Kd 5.74 CHEMBL
NUAK family SNF1-like kinase 2 Kinase Kd 5.34 CHEMBL
ATP-binding cassette sub-family G member 2 Transporter IC50 5.96 CHEMBL
Tyrosine-protein kinase TXK Kinase Kd 5.22 CHEMBL
Mitogen-activated protein kinase kinase kinase 3 Kinase Kd 5.68 CHEMBL
Serine/threonine-protein kinase Chk2 Kinase Kd 6.10 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase Kd 5.42 SCIENTIFIC LITERATURE
Serine/threonine-protein kinase NLK Kinase Kd 5.38 CHEMBL
Cruzipain Enzyme IC50 4.06 CHEMBL
Tubulin alpha-1A chain Structural Kd 6.39 CHEMBL
Serine/threonine-protein kinase ULK3 Kinase Kd 5.85 CHEMBL

External reference:

IDSource
D000077156 MESH_DESCRIPTOR_UI
4021392 VUID
N0000148810 NUI
C1122962 UMLSCUI
D01977 KEGG_DRUG
398685009 SNOMEDCT_US
328134 RXNORM
d04868 MMSL
17257 MMSL
4021392 VANDF
407100002 SNOMEDCT_US
009981 NDDF
CHEMBL939 ChEMBL_ID
DB00317 DRUGBANK_ID
S65743JHBS UNII
8204 INN_ID
IRE PDB_CHEM_ID
CHEBI:49668 CHEBI
123631 PUBCHEM_CID
4941 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
IRESSA HUMAN PRESCRIPTION DRUG LABEL 1 0310-0482 TABLET, COATED 250 mg ORAL NDA 18 sections