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Drug

D1377 | Imatinib

Molecular Formula C29H31N7O
Molecular Weight 493.6
Structure
State solid
Clearance * 8 L/h [50-year-old CML and GIST patient weighing 50 kg] * 14 L/h [50-year-old CML and GIST patient weighing 100 kg]
Route of elimination Imatinib elimination is predominately in the feces, mostly as metabolites. 81% of the dose is eliminated within 7 days, in feces (68% of the dose) and urine (13% of the dose). Unchanged imatinib accounted for 25% of the dose (5% urine, 20% faces), the remainder being metabolites.
Protein binding 95% protein bound, mostly to albumin and alpha-1-acid glycoprotein.
Half life Following oral administration in healthy volunteers, the elimination half-lives of imatinib and its major active metabolite, the N-demethyl derivative (CGP74588) are approximately 18 and 40 hours, respectively.
Absorption The pharmacokinetics in CML and GIST patients are similar. Imatinib is well absorbed with mean absolute bioavailability is 98% and maximum plasma levels achieved within 2-4 hours of dosing
Trade names Gleevec, Glivec
Description a small molecule kinase inhibitor

L

L01XE01 Imatinib


[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 25.7 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 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). Rotenone (2µM) was used as 100% baseline for complex I inhibition. Negative 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
GLYCOLYSIS 249
SWELLING ND 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 ) Negative EC20 36

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase 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). Rotenone (2µM) was used as 100% baseline for complex I inhibition. Negative EC20 36
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
Cytochrome c 163.6 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 9 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H302 (22.22%): Harmful if swallowed [Warning Acute toxicity, oral]


H315 (11.11%): Causes skin irritation [Warning Skin corrosion/irritation]


H319 (11.11%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]


H341 (55.56%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]


H351 (77.78%): Suspected of causing cancer [Warning Carcinogenicity]


H360 (55.56%): May damage fertility or the unborn child [Danger Reproductive toxicity]


H361 (33.33%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]


H362 (55.56%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]


H373 (22.22%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]


H411 (22.22%): 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, P263, P264, P270, P273, P280, P281, P301+P312, P302+P352, P305+P351+P338, P308+P313, P314, P321, P330, P332+P313, P337+P313, P362, P391, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)


  • 1080014-82-9 112GI019 12810-EP2269994A1
    12810-EP2270008A1 12810-EP2272827A1 12810-EP2275412A1
    12810-EP2275413A1 12810-EP2277865A1 12810-EP2287156A1
    12810-EP2289892A1 12810-EP2291366A2 12810-EP2292234A1
    12810-EP2292617A1 12810-EP2305667A2 12810-EP2308855A1
    12810-EP2311807A1 12810-EP2311821A1 12810-EP2311840A1
    12810-EP2316831A1 12810-EP2316832A1 12810-EP2316833A1
    152459-95-5 1iep 1xbb
    4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYL]-BENZAMIDE 4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide 4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3- pyridinyl)-2-pyrimidinyl]amino]phenyl]benzamide
    4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-phenyl]benzamide 4-[(4-methyl-1-piperazinyl)-methyl]-N-{4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]-amino]-phenyl)-benzamide 4-[(4-methyl-1-piperazinyl)-methyl]-N-{4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]-amino]-phenyl}-benzamide
    4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[(4-(3-pyridinyl)-2-pyrimidinyl]amino]-phenyl]benzamide 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide methanesulfonate
    4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]benzamide 4-[(4-methyl-1-piperazinyl)methyl]-n[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide 4-[(4-methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide
    4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide 4-[(4-methylpiperazin-1-yl)methyl]-N-{4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl}benzamide 459I955
    AB0044023 AB00698388-07 AB00698388-10
    AB00698388-11 AB00698388-12 AB00698388-13
    AB00698388_15 AB00698388_16 AC-524
    ACMC-20a8ej AK107630 AKOS000280662
    AM20090646 ANW-61817 API0024674
    AX8134347 BCP01542 BCP9000775
    BCPP000205 BDBM13530 BIDD:GT0047
    BKJ8M8G5HI BRD-K92723993-066-02-9 BRD-K92723993-066-04-5
    Benzamide, 4-((4-methyl)-1-piperazinyl)methyl)-N-(4-methyl-3-((4-(3-pyridinyl)-2-pyrimidinyl)amino)phenyl)- Benzamide, 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]- (9CI) Benzamide, 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-, methanesulfonate (1:1);4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide monomethanesulfonate;imatinib;Imatinib mesylate
    C29H31N7O CCG-101289 CCRIS 9076
    CGP 57148B CGP-57148 CHEBI:45783
    CHEMBL941 CS-0964 CTK8B9010
    Cgp 57148 D08066 DB00619
    DTXSID3037125 ES-0058 EX-A063
    FT-0651483 GTPL5687 Glamox (TN)
    Gleevec (TN) (Novartis) Gleevec(TM) Glivec
    HMS2089D03 HMS3244P06 HMS3244P10
    HMS3244P14 HMS3656K04 HMS3715P03
    HY-15463 I0906 IMATINIB
    Imatinib Imatinib (Gleevec) Imatinib (INN)
    Imatinib (STI571) Imatinib - Gleevec Imatinib Methansulfonate
    Imatinib [INN:BAN] Imatinib free base Imatinib, 21
    KS-00000GF2 KSC919A1B Kinome_3724
    LS-182208 LS-187106 MCULE-2384256888
    MRF-0000449 N-(3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)-4-methylphenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide N-(4-Methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide
    N-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)-4-[(4-methylpiperazin-1-yl)methyl]benzamide NCGC00159456-02
    NCGC00159456-03 NCGC00159456-04 NCGC00159456-05
    NCGC00159456-06 NCGC00159456-07 NCGC00159456-09
    NCGC00159456-16 NS00009172 NSC-743414
    NSC-759854 NSC743414 NSC759854
    Pharmakon1600-01502276 Q-201231 Q177094
    QCR-269 S2475 SB17306
    SCHEMBL3827 SR-01000763561 SR-01000763561-4
    SR-01000763561-6 ST 1571 ST1571
    STI STI 571 STI-571
    STI571 STK617705 SW197805-5
    UNII-BKJ8M8G5HI VCC905240 W-3956
    Z1551429727 ZINC19632618 alpha-(4-Methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-p-tolu-p-toluidide
    alpha-(4-methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-p-toluidide benzamide, 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]- cid_5291
    imatinib-CD3 sti-571

    DrugBank DB00619
    CAS Number 1080014-82-9, 1092942-82-9, 1134803-18-1, 152459-95-5, 220127-57-1
    PubChem Compound 5291