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Showing metabocard for Erlotinib (HMDB0014671)
Record Information | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Version | 4.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Status | Expected but not Quantified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Creation Date | 2012-09-06 15:16:50 UTC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Update Date | 2019-01-11 19:34:04 UTC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
HMDB ID | HMDB0014671 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Secondary Accession Numbers |
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Metabolite Identification | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Common Name | Erlotinib | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Description | Erlotinib hydrochloride (trade name Tarceva, Genentech/OSIP, originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. Similar to gefitinib, erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. Erlotinib has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The study suggests that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Structure | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Synonyms |
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Chemical Formula | C22H23N3O4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Average Molecular Weight | 393.4357 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Monoisotopic Molecular Weight | 393.168856239 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
IUPAC Name | N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Traditional Name | erlotinib | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CAS Registry Number | 183321-74-6 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
SMILES | COCCOC1=C(OCCOC)C=C2C(NC3=CC=CC(=C3)C#C)=NC=NC2=C1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
InChI Identifier | InChI=1S/C22H23N3O4/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
InChI Key | AAKJLRGGTJKAMG-UHFFFAOYSA-N | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Chemical Taxonomy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Description | This compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Kingdom | Organic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Super Class | Organoheterocyclic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Class | Diazanaphthalenes | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sub Class | Benzodiazines | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Direct Parent | Quinazolinamines | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Alternative Parents | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Substituents |
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Molecular Framework | Aromatic heteropolycyclic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
External Descriptors |
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Ontology | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Disposition | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Process | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Role | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Physical Properties | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
State | Solid | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Experimental Properties |
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Predicted Properties |
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Spectra |
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Biological Properties | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Cellular Locations |
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Biospecimen Locations |
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Tissue Locations | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pathways | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Normal Concentrations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Abnormal Concentrations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Associated Disorders and Diseases | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Disease References | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Associated OMIM IDs | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
External Links | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
DrugBank ID | DB00530 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Phenol Explorer Compound ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
FoodDB ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
KNApSAcK ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Chemspider ID | 154044 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
KEGG Compound ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
BioCyc ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
BiGG ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Wikipedia Link | Erlotinib | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
METLIN ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PubChem Compound | 176870 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDB ID | AQ4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ChEBI ID | 114785 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
References | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Material Safety Data Sheet (MSDS) | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
General References |
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Only showing the first 10 proteins. There are 11 proteins in total.
Enzymes
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
- Gene Name:
- CYP3A4
- Uniprot ID:
- P08684
- Molecular weight:
- 57255.585
References
- van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
- Johnson JR, Cohen M, Sridhara R, Chen YF, Williams GM, Duan J, Gobburu J, Booth B, Benson K, Leighton J, Hsieh LS, Chidambaram N, Zimmerman P, Pazdur R: Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res. 2005 Sep 15;11(18):6414-21. [PubMed:16166415 ]
- Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. [PubMed:17575239 ]
- Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, Cagnoni PJ: Effects of smoking on the pharmacokinetics of erlotinib. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2166-71. [PubMed:16609030 ]
- General function:
- Involved in transmembrane receptor protein tyrosine kinase activity
- Specific function:
- Isoform 2 may act as an antagonist of EGF action
- Gene Name:
- EGFR
- Uniprot ID:
- P00533
- Molecular weight:
- 134276.2
References
- Kim TE, Murren JR: Erlotinib OSI/Roche/Genentech. Curr Opin Investig Drugs. 2002 Sep;3(9):1385-95. [PubMed:12498017 ]
- Laird AD, Cherrington JM: Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents. Expert Opin Investig Drugs. 2003 Jan;12(1):51-64. [PubMed:12517254 ]
- Delbaldo C, Faivre S, Raymond E: [Epidermal growth factor inhibitors]. Rev Med Interne. 2003 Jun;24(6):372-83. [PubMed:12814826 ]
- Bulgaru AM, Mani S, Goel S, Perez-Soler R: Erlotinib (Tarceva): a promising drug targeting epidermal growth factor receptor tyrosine kinase. Expert Rev Anticancer Ther. 2003 Jun;3(3):269-79. [PubMed:12820772 ]
- Akita RW, Sliwkowski MX: Preclinical studies with Erlotinib (Tarceva). Semin Oncol. 2003 Jun;30(3 Suppl 7):15-24. [PubMed:12840797 ]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development.
- Gene Name:
- CYP1B1
- Uniprot ID:
- Q16678
- Molecular weight:
- 60845.33
References
- van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
- Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. [PubMed:17575239 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
- Gene Name:
- CYP2D6
- Uniprot ID:
- P10635
- Molecular weight:
- 55768.94
References
- van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
- Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. [PubMed:17575239 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
- Gene Name:
- CYP3A5
- Uniprot ID:
- P20815
- Molecular weight:
- 57108.065
References
- van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
- Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. [PubMed:17575239 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
- Gene Name:
- CYP1A1
- Uniprot ID:
- P04798
- Molecular weight:
- 58164.815
References
- van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
- Johnson JR, Cohen M, Sridhara R, Chen YF, Williams GM, Duan J, Gobburu J, Booth B, Benson K, Leighton J, Hsieh LS, Chidambaram N, Zimmerman P, Pazdur R: Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res. 2005 Sep 15;11(18):6414-21. [PubMed:16166415 ]
- Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. [PubMed:17575239 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
- Gene Name:
- CYP1A2
- Uniprot ID:
- P05177
- Molecular weight:
- 58406.915
References
- van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
- Lu JF, Eppler SM, Wolf J, Hamilton M, Rakhit A, Bruno R, Lum BL: Clinical pharmacokinetics of erlotinib in patients with solid tumors and exposure-safety relationship in patients with non-small cell lung cancer. Clin Pharmacol Ther. 2006 Aug;80(2):136-45. [PubMed:16890575 ]
- Johnson JR, Cohen M, Sridhara R, Chen YF, Williams GM, Duan J, Gobburu J, Booth B, Benson K, Leighton J, Hsieh LS, Chidambaram N, Zimmerman P, Pazdur R: Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res. 2005 Sep 15;11(18):6414-21. [PubMed:16166415 ]
- Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. [PubMed:17575239 ]
- Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, Cagnoni PJ: Effects of smoking on the pharmacokinetics of erlotinib. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2166-71. [PubMed:16609030 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
- Gene Name:
- CYP2C8
- Uniprot ID:
- P10632
- Molecular weight:
- 55824.275
References
- van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
- Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, Cagnoni PJ: Effects of smoking on the pharmacokinetics of erlotinib. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2166-71. [PubMed:16609030 ]
- General function:
- Involved in sequence-specific DNA binding transcription factor activity
- Specific function:
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes
- Gene Name:
- NR1I2
- Uniprot ID:
- O75469
- Molecular weight:
- 49761.2
References
- Harmsen S, Meijerman I, Beijnen JH, Schellens JH: Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009 Jun;64(1):35-43. doi: 10.1007/s00280-008-0842-3. Epub 2008 Oct 7. [PubMed:18839173 ]
- van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
Transporters
- General function:
- Involved in ATP binding
- Specific function:
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
- Gene Name:
- ABCB1
- Uniprot ID:
- P08183
- Molecular weight:
- 141477.3
References
- Marchetti S, de Vries NA, Buckle T, Bolijn MJ, van Eijndhoven MA, Beijnen JH, Mazzanti R, van Tellingen O, Schellens JH: Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008 Aug;7(8):2280-7. doi: 10.1158/1535-7163.MCT-07-2250. [PubMed:18723475 ]
- General function:
- Involved in ATP binding
- Specific function:
- Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
- Gene Name:
- ABCG2
- Uniprot ID:
- Q9UNQ0
- Molecular weight:
- 72313.5
References
- Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y: Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009 Sep;100(9):1701-7. doi: 10.1111/j.1349-7006.2009.01213.x. Epub 2009 May 12. [PubMed:19493273 ]
Only showing the first 10 proteins. There are 11 proteins in total.