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Drug

D0440 | gefitinib

Molecular Formula C22H24ClFN4O3
Molecular Weight 446.9
Structure
State solid
Clearance * 595 mL/min [IV administration]
Volume of distribution * 1400 L [IV administration]
Route of elimination Elimination is by metabolism (primarily CYP3A4) and excretion in feces. Excretion is predominantly via the feces (86%), with renal elimination of drug and metabolites accounting for less than 4% of the administered dose.
Protein binding 90% primarily to serum albumin and alpha 1-acid glycoproteins (independent of drug concentrations).
Half life 48 hours [IV administration]
Absorption Absorbed slowly after oral administration with a mean bioavailability of 60%. Peak plasma levels occurs 3-7 hours post-administration. Food does not affect the bioavailability of gefitinib.
Trade names Iressa
Description an EGFR inhibitor

L

L01XE02 Gefitinib


[L01XE] Protein kinase inhibitors


[L01X] OTHER ANTINEOPLASTIC AGENTS


[L01] ANTINEOPLASTIC AGENTS


[L] Antineoplastic and immunomodulating agents

Toxicity Dose Time Species Model Method Action Positive criterion Reference
MEMBRANE POTENTIAL 9.6 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
RESPIRATION 269.6 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. decrease EC20 36
RESPIRATION ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. Negative EC20 36
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex I activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex IV activity decrease p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex V activity decrease p < 0.001 3
SWELLING 63.6 µM 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) increase EC20 36

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase 50 μM bovine heart mitochondria Measurement of complex I activity Negative p < 0.05 3
NADH:ubiquinone reductase 269.6 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. inhibit EC20 36
Succinate dehydrogenase 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
Succinate dehydrogenase ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. Negative EC20 36
Quinol--cytochrome-c reductase 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
Cytochrome c oxidase 50 μM bovine heart mitochondria Measurement of complex IV activity inhibitor p < 0.05 3
ATP synthase 50 μM bovine heart mitochondria Measurement of complex V activity inhibitor p < 0.001 3
Cytochrome c 50.5 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes
Danger

Aggregated GHS information provided by 49 companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]


H315 (57.14%): Causes skin irritation [Warning Skin corrosion/irritation]


H318 (55.1%): Causes serious eye damage [Danger Serious eye damage/eye irritation]


H351 (57.14%): Suspected of causing cancer [Warning Carcinogenicity]


H361 (61.22%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]


H373 (57.14%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]


H400 (36.73%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]


H411 (55.1%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P201, P202, P260, P264, P270, P273, P280, P281, P301+P312, P302+P352, P305+P351+P338, P308+P313, P310, P314, P321, P330, P332+P313, P362, P391, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)


  • 15215-EP2269994A1 15215-EP2272827A1 15215-EP2272832A1
    15215-EP2275413A1 15215-EP2277865A1 15215-EP2280006A1
    15215-EP2281813A1 15215-EP2281815A1 15215-EP2287156A1
    15215-EP2292234A1 15215-EP2292615A1 15215-EP2298768A1
    15215-EP2298778A1 15215-EP2301533A1 15215-EP2301933A1
    15215-EP2305640A2 15215-EP2305671A1 15215-EP2311807A1
    15215-EP2311827A1 15215-EP2311840A1 15215-EP2316832A1
    15215-EP2316833A1 184475-35-2 3-Chloro-4-Fluoro-N-[(4z)-7-Methoxy-6-(3-Morpholin-4-Ylpropoxy)quinazolin-4(1h)-Ylidene]aniline
    32333-EP2281815A1 32333-EP2292615A1 32333-EP2301933A1
    32333-EP2305640A2 32333-EP2305671A1 32333-EP2311827A1
    4-(3'-Chloro-4'-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline 4-(3'-chloro-4'-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)-quinazoline 4-(3-CHLORO-4-FLUOROANILINO)-7-METHOXY-6-(3-MORPHOLINOPROPOXY)QUINAZOLINE
    4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)- 4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-4-morpholin)propoxy)- 4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-
    4-[(3-Chloro-4-fluorophenyl)amino]-7-methoxy-6-(3-morpholinopropoxy)quinazoline 475G352 4CA-0562
    6-(3-morpholinopropoxy)-N-(3-chloro-4-fluorophenyl)-7-methoxyquinazolin-4-amine A812870 AB0000095
    AB01273954-01 AB01273954-02 AB01273954-03
    AB01273954_04 AB20814 ABP000855
    AC-1556 AK-72948 AKOS000280752
    AM20090619 AMX10169 AOB6917
    API0002810 BCB03_000781 BCP01365
    BCP9000718 BCPP000221 BDBM5447
    BR-72948 C-22438 CAS-184475-35-2
    CC-28943 CCG-220642 CCRIS 9011
    CG0031 CHEBI:49668 CHEMBL939
    CS-0124 CTK7A0364 CU-00000000396-1
    D01977 DB00317 DSSTox_CID_21034
    DSSTox_GSID_41034 DSSTox_RID_79614 DTXSID8041034
    EBD446 EC-000.2409 EN002708
    FT-0081035 FT-0602325 G-4408
    GP9843 GTPL4941 Gefitini
    Gefitinib Gefitinib (JAN/USAN/INN) Gefitinib - Iressa
    Gefitinib [USAN:INN:BAN] Gefitinib [USAN] Gefitinib for system suitability, EuropePharmacopoeia (EP) Reference Standard
    Gefitinib, >=98% (HPLC) Gefitinib, EuropePharmacopoeia (EP) Reference Standard Gefitinib, Iressa, ZD1839
    Gefitinib,ZD-1839,Iressa Gefitinib/ZD-1839,Iressa H018
    HMS2089B19 HMS3244M21 HMS3244M22
    HMS3244N21 HMS3413H08 HMS3654A07
    HMS3677H08 HMS3714A05 HMS3748E17
    HY-50895 IRE IRRESSA
    Iressa Iressa Iressa (AstraZeneca)
    Iressa (TN) Iressa(TM) Iressa|||ZD 1839
    Irressat J10250 K00240
    KBioSS_002241 KS-00000E11 KS-1204
    Kinome_3321 Kinome_3322 LS-139916
    MCULE-6951584187 MFCD04307832 MLS003899193
    N-(3-Chloro-4-fluoro-phenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine N-(3-Chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine N-(3-chloranyl-4-fluoranyl-phenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine;
    N-(3-chloro-4-fluoro-phenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)-4-quinazolinamine N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine
    N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-4-quinazolinamine N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine NCGC00159455-02
    NCGC00159455-03 NCGC00159455-04 NCGC00159455-05
    NCGC00159455-06 NCGC00159455-08 NCGC00159455-09
    NCGC00159455-14 NSC-715055 NSC-759856
    NSC715055 NSC759856 Pharmakon1600-01502274
    Q-201149 Q417824 QCR-105
    S-2176 S65743JHBS SC-18023
    SCHEMBL7866 SMR002204119 SR-00000000262
    SR-00000000262-2 SR-00000000262-3 ST2413546
    STK621310 SW199108-4 SY002154
    SYN1042 Tox21_111683 Tox21_111683_1
    UNII-S65743JHBS XGALLCVXEZPNRQ-UHFFFAOYSA-N Z1551429741
    ZD 1839 ZD-1839 ZD1839
    ZINC19632614 cid_123631 gefitinib (iressa)
    gefitinib (zd1839) gefitinibum nchembio866-comp14
    s1025

    DrugBank Name gefitinib
    DrugBank DB00317
    CAS Number 184475-35-2, 857091-32-8
    PubChem Compound 123631
    KEGG Drug D01977
    ChEBI 49668
    PharmGKB PA131301952
    ChemSpider 110217
    BindingDB 5447.0
    TTD DAP000657
    Wikipedia Gefitinib