Icotinib
Identification
- Name
- Icotinib
- Accession Number
- DB11737
- Description
Icotinib is a potent and specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) Icotinib was approved in China by the SFDA in June, 2011 and in January 2014, Beta Pharma, Inc. was given a “May Proceed” from the US FDA to conduct a Phase I study for the evaluation of icotinib as a treatment of EGFR+ Non-Small Cell Lung Cancer (NSCLC).
- Type
- Small Molecule
- Groups
- Experimental, Investigational
- Structure
Structure for Icotinib (DB11737)
- Weight
- Average: 391.427
Monoisotopic: 391.153206168 - Chemical Formula
- C22H21N3O4
- Synonyms
- BPI-2009
- External IDs
- BPI-2009
Pharmacology
- Indication
Icotinib hydrochloride is a novel epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy.
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- Pharmacodynamics
In vitro: Icotinib inhibits EGFR activity in a dose-dependent manner, with an IC50 value of 5 nM and complete inhibition at 62.5 nM. Icotinib selectively solely inhibits the EGFR members including the wild type and mutants with inhibition efficacies of 61-99%. Icotinib blocks EGFR-mediated intracellular tyrosine phosphorylation in human epidermoid carcinoma A431 cells in a dose-dependent manner. Meanwhile, in the proliferation assay performed on A431, BGC-823, A549, H460, HCT8, KB and Bel-7402 cell lines, it was found that the relative sensitivity of cell lines to Icotinib is A431 > BGC-823 > A549 > H460 > KB > HCT8 and Bel-7402. Icotinib exhibits a broad spectrum of antitumor activity and it is especially effective against tumors expressing higher levels of EGFR. In vivo: In vivo studies demonstrated that Icotinib exhibited potent dose-dependent antitumor effects in nude mice carrying a variety of human tumor-derived xenografts. The drug was well tolerated at doses up to 120 mg/kg/day in mice without mortality or significant body weight loss during the treatment. A head to head randomized, double blind phase III trial using Gefitinib as an active control for patients with advanced non-small cell lung cancer (NSCLC) was finished recently (Trial registration ID: NCT01040780).
- Mechanism of action
Icotinib is a highly selective, first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) which binds reversibly to the ATP binding site of the EGFR protein, preventing completion of the signal transduction cascade. EGFR is an oncogenic receptor and patients with activating somatic mutations, such as an exon 19 deletion or exon 21 L858R mutation, within the tyrosine kinase domain display unchecked cell proliferation.
Target Actions Organism UEpidermal growth factor receptor antagonistHumans - Absorption
Bioavailability = 52%
- Volume of distribution
the volume of distribution was calculated as Vz/F = 115.00 ± 63.26 l
- Protein binding
Icotinib binds to Sudlow's site I in subdomain IIA of Human Serum Albumin (HSA) molecule, resulting in the formation of icotinib-HSA complexes.
- Metabolism
Hepatic (mainly CYP3A4, less CYP1A2)
- Route of elimination
>90% via faeces, 9% via urine
- Half-life
5.5 hrs
- Clearance
the clearance was calculated as CL/F = 13.30 ± 4.78 l/h
- Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More- Toxicity
The most common toxicities reported are skin-related events and diarrhea.
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Unlock Additional DataAbaloparatide The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Icotinib. Abametapir The serum concentration of Icotinib can be increased when it is combined with Abametapir. Abatacept The metabolism of Icotinib can be increased when combined with Abatacept. Acalabrutinib The metabolism of Icotinib can be decreased when combined with Acalabrutinib. Acetaminophen The serum concentration of Acetaminophen can be increased when it is combined with Icotinib. Adalimumab The metabolism of Icotinib can be increased when combined with Adalimumab. Alfentanil The metabolism of Alfentanil can be increased when combined with Icotinib. Alprazolam The metabolism of Alprazolam can be increased when combined with Icotinib. Ambrisentan The metabolism of Ambrisentan can be increased when combined with Icotinib. Amitriptyline The metabolism of Amitriptyline can be increased when combined with Icotinib. Additional Data Available- Extended DescriptionExtended DescriptionAvailable for Purchase
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - SeveritySeverityAvailable for Purchase
A severity rating for each drug interaction, from minor to major.
Learn more - Evidence LevelEvidence LevelAvailable for Purchase
A rating for the strength of the evidence supporting each drug interaction.
Learn more - ActionActionAvailable for Purchase
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- Food Interactions
- Not Available
Products
Purchasing individual compounds or compound libraries for your research?
Learn More- Product Ingredients
Ingredient UNII CAS InChI Key Icotinib hydrochloride JTD32I0J83 1204313-51-8 PNNGXMJMUUJHAV-UHFFFAOYSA-N
Categories
- ATC Codes
- L01XE48 — Icotinib
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Crown Compounds
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Inducers
- Cytochrome P-450 CYP3A5 Inducers (moderate)
- Cytochrome P-450 CYP3A5 Inducers (weak)
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Substrates
- Ethers
- Ethers, Cyclic
- Heterocyclic Compounds, Fused-Ring
- Protein Kinase Inhibitors
- Tyrosine Kinase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- 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
- Aniline and substituted anilines / Aminopyrimidines and derivatives / Alkyl aryl ethers / Imidolactams / Heteroaromatic compounds / Secondary amines / Oxacyclic compounds / Dialkyl ethers / Azacyclic compounds / Acetylides show 2 more
- Substituents
- Acetylide / Alkyl aryl ether / Amine / Aminopyrimidine / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Dialkyl ether / Ether show 13 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
Chemical Identifiers
- UNII
- 9G6U5L461Q
- CAS number
- 610798-31-7
- InChI Key
- QQLKULDARVNMAL-UHFFFAOYSA-N
- InChI
- InChI=1S/C22H21N3O4/c1-2-16-4-3-5-17(12-16)25-22-18-13-20-21(14-19(18)23-15-24-22)29-11-9-27-7-6-26-8-10-28-20/h1,3-5,12-15H,6-11H2,(H,23,24,25)
- IUPAC Name
- N-(3-ethynylphenyl)-7H,8H,10H,11H,13H,14H-1,4,7,10-tetraoxacyclododeca[2,3-g]quinazolin-4-amine
- SMILES
- C#CC1=CC=CC(NC2=NC=NC3=CC4=C(OCCOCCOCCO4)C=C23)=C1
References
- General References
- Tan F, Shi Y, Wang Y, Ding L, Yuan X, Sun Y: Icotinib, a selective EGF receptor tyrosine kinase inhibitor, for the treatment of non-small-cell lung cancer. Future Oncol. 2015;11(3):385-97. doi: 10.2217/fon.14.249. [PubMed:25675121]
- Tan F, Shen X, Wang D, Xie G, Zhang X, Ding L, Hu Y, He W, Wang Y, Wang Y: Icotinib (BPI-2009H), a novel EGFR tyrosine kinase inhibitor, displays potent efficacy in preclinical studies. Lung Cancer. 2012 May;76(2):177-82. doi: 10.1016/j.lungcan.2011.10.023. Epub 2011 Nov 22. [PubMed:22112293]
- Liu D, Jiang J, Zhang L, Tan F, Wang Y, Hu P: Metabolite characterization of a novel anti-cancer agent, icotinib, in humans through liquid chromatography/quadrupole time-of-flight tandem mass spectrometry. Rapid Commun Mass Spectrom. 2011 Aug 15;25(15):2131-40. doi: 10.1002/rcm.5061. [PubMed:21732454]
- Guan YS, He Q, Li M: Icotinib: activity and clinical application in Chinese patients with lung cancer. Expert Opin Pharmacother. 2014 Apr;15(5):717-28. doi: 10.1517/14656566.2014.890183. Epub 2014 Mar 4. [PubMed:24588695]
- Zhang HX, Xiong HX, Li LW: Investigation on the protein-binding properties of icotinib by spectroscopic and molecular modeling method. Spectrochim Acta A Mol Biomol Spectrosc. 2016 May 15;161:88-94. doi: 10.1016/j.saa.2016.02.014. Epub 2016 Feb 23. [PubMed:26963729]
- Icotonib approval [Link]
- Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer [Link]
- External Links
- PubChem Compound
- 22024915
- PubChem Substance
- 347828095
- ChemSpider
- 10762174
- BindingDB
- 50391089
- ChEMBL
- CHEMBL2087361
- ZINC
- ZINC000043207566
- PharmGKB
- PA166114460
- Wikipedia
- Icotinib
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Neoplasms, Lung 1 4 Completed Treatment Non-Small Cell Lung Carcinoma (NSCLC) 1 4 Not Yet Recruiting Treatment Adenocarcinomas / Carcinoma NOS / Non-Small Cell Lung Carcinoma (NSCLC) 1 4 Suspended Treatment Non-Small Cell Lung Carcinoma (NSCLC) 1 4 Unknown Status Treatment Adenocarcinomas / EGFR Positive Non-small Cell Lung Cancer 3 4 Unknown Status Treatment Neoplasms, Therapy-Associated 1 4 Unknown Status Treatment Non-Small Cell Lung Carcinoma (NSCLC) 5 3 Completed Treatment Brain Metastasis / Non-Small Cell Lung Carcinoma (NSCLC) 1 3 Completed Treatment Malignancies 1 3 Completed Treatment Non-Small Cell Lung Carcinoma (NSCLC) 3
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0126 mg/mL ALOGPS logP 2.88 ALOGPS logP 3.03 ChemAxon logS -4.5 ALOGPS pKa (Strongest Acidic) 16.14 ChemAxon pKa (Strongest Basic) 4.62 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 7 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 74.73 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 105.82 m3·mol-1 ChemAxon Polarizability 42.08 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
- Gene Name
- EGFR
- Uniprot ID
- P00533
- Uniprot Name
- Epidermal growth factor receptor
- Molecular Weight
- 134276.185 Da
References
- MedChem Express [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase 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 react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Zhang T, Zhang K, Ma L, Li Z, Wang J, Zhang Y, Lu C, Zhu M, Zhuang X: Metabolic Pathway of Icotinib In Vitro: The Differential Roles of CYP3A4, CYP3A5, and CYP1A2 on Potential Pharmacokinetic Drug-Drug Interaction. J Pharm Sci. 2018 Apr;107(4):979-983. doi: 10.1016/j.xphs.2017.12.007. Epub 2017 Dec 14. [PubMed:29247736]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Data supporting this enzyme action are limited to an in vitro study.
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- 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 un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Zhang T, Zhang K, Ma L, Li Z, Wang J, Zhang Y, Lu C, Zhu M, Zhuang X: Metabolic Pathway of Icotinib In Vitro: The Differential Roles of CYP3A4, CYP3A5, and CYP1A2 on Potential Pharmacokinetic Drug-Drug Interaction. J Pharm Sci. 2018 Apr;107(4):979-983. doi: 10.1016/j.xphs.2017.12.007. Epub 2017 Dec 14. [PubMed:29247736]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInducer
- General Function
- Oxygen binding
- 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 un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Zhuang X, Zhang T, Yue S, Wang J, Luo H, Zhang Y, Li Z, Che J, Yang H, Li H, Zhu M, Lu C: Allosteric activation of midazolam CYP3A5 hydroxylase activity by icotinib - Enhancement by ketoconazole. Biochem Pharmacol. 2016 Dec 1;121:67-77. doi: 10.1016/j.bcp.2016.09.012. Epub 2016 Sep 22. [PubMed:27666601]
- Zhang T, Zhang K, Ma L, Li Z, Wang J, Zhang Y, Lu C, Zhu M, Zhuang X: Metabolic Pathway of Icotinib In Vitro: The Differential Roles of CYP3A4, CYP3A5, and CYP1A2 on Potential Pharmacokinetic Drug-Drug Interaction. J Pharm Sci. 2018 Apr;107(4):979-983. doi: 10.1016/j.xphs.2017.12.007. Epub 2017 Dec 14. [PubMed:29247736]
Drug created on October 20, 2016 14:43 / Updated on June 12, 2020 10:53
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