Drug Details
| General Information of the Drug (ID: DR2172) | ||||
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| Name |
Afatinib
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| Synonyms |
Afatinib; 439081-18-2; 850140-72-6; BIBW2992; Tovok; Tomtovok; BIBW 2992; BIBW-2992; Afatinib (BIBW2992); (S,E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide; Afatinib free base; N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-2-Butenamide; UNII-41UD74L59M; C24H25ClFN5O3; (2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[(3S)-tetrahydrofuran-3-yloxy]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide; CHEMBL1173655; CHEBI:61390; 41UD74L59M; 850140-72-6 (free base); S1011; (2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[(3S)-oxolan-3-yloxy]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide; (S,E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide; (S)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide; (E)-N-[4-(3-chloro-4-fluoroanilino)-7-[(3S)-oxolan-3-yl]oxyquinazolin-6-yl]-4-(dimethylamino)but-2-enamide; (S,E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide.; 2-Butenamide, N-(4-((3-chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydro-3-furanyl)oxy)-6-quinazolinyl)-4-(dimethylamino)-, (2E)-; Afatinib [USAN:INN]; afatinibum; MFCD12407405; (E)-4-dimethylamino-but-2-enoic acid-(4-(3-chloro-4-fluoro-phenylamino)-7-((S)-tetrahydrofuran-3-yloxy)-quinazolin-6-yl)-amide; (E)-4-Dimethylamino-but-2-enoic acid-[4-(3-chloro-4-fluoro-phenylamino)-7-((S)-tetrahydrofuran-3-yloxy)-quinazolin-6-yl]-amide; 2-Butenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-, (2E)-; Afatinib, Free Base; BIBW2992,Afatinib; PubChem22403; Afatinib (USAN/INN); BIBW2992 - Afatinib; Tovok; ; ; BIBW 2992; (2E)-N-(4-(3-chloro-4-fluoroanilino)-7-(((3S)-oxolan-3-yl)oxy)quinoxazolin-6-yl)-4-(dimethylamino)but-2-enamide; cc-109; MLS006010000; GTPL5667; CHEBI:94698; DTXSID20893451; EX-A065; QCR-169; BCPP000338; AOB87785; BCP01779; ZINC3976838; BIBW2992/Tovok,BIBW-2992; 3123AC; ABP000859; BDBM50322823; NSC750691; NSC799327; Afatinib(cis-trans isomerismtautomers); AKOS015850681; AKOS015904219; AKOS025149636; BCP9000407; CCG-264776; DB08916; EX-8656; NSC-750691; NSC-799327; PB28439; NCGC00185000-01; (2e)-n-(4-((3-chloro-4-fluorophenyl)amino)-7-(((3s)-tetrahydro-3-furanyl)oxy)-6-quinazolinyl)-4-(dimethylamino)-2-butenamide; AC-26079; AC-27018; AM808098; DS-14172; SMR004701084; AB0033685; SW219248-1; X7366; A15572; D09724; Q-3651; AB01565886_02; 081B182; SR-01000941576; J-500781; J-502300; Q4688818; SR-01000941576-1; BRD-K66175015-001-01-7; (2E)-N-[4-(3-Chloro-4-fluoroanilino)-7-[[(3S)-oxolane-3-yl]oxy]quinazoline-6-yl]-4-(dimethylamino)-2-buteneamide; (E)-4-dimethylamino-but-2-enoic acid-(4-(3-chloro-4-fluoro-phenylamino)-7-((S)-tetrahydrofuran-3-yloxy)-quinazolin-6yl)-amide; (R,E)-N-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide; (S)-N-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide; N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-[[(3''S'')-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4(dimethylamino)-2-butenamide
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| Molecular Type |
Small molecule
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| Disease | Lung cancer [ICD-11: 2C25] | Approved | [1] | |
| Structure |
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Click to Download Mol2D MOL |
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| Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product | ||||
| Formula |
C24H25ClFN5O3
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| PubChem CID | ||||
| Canonical SMILES |
CN(C)CC=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OC4CCOC4
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| InChI |
1S/C24H25ClFN5O3/c1-31(2)8-3-4-23(32)30-21-11-17-20(12-22(21)34-16-7-9-33-13-16)27-14-28-24(17)29-15-5-6-19(26)18(25)10-15/h3-6,10-12,14,16H,7-9,13H2,1-2H3,(H,30,32)(H,27,28,29)/b4-3+/t16-/m0/s1
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| InChIKey |
ULXXDDBFHOBEHA-CWDCEQMOSA-N
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| CAS Number |
CAS 850140-72-6
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| ChEBI ID | ||||
| TTD Drug ID | ||||
| DrugBank ID | ||||
| Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally | ||||||
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| α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug | ||||||
| Celastrol | Celastrus strigillosus | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [2] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Biological
Regulation |
Induction | Mitochondrial Ca2+ overload | ||||
| Induction | ROS accumulation | |||||
| In-vitro Model | NCI-H23 | CVCL_1547 | Lung adenocarcinoma | Homo sapiens | ||
| NCI-H292 | CVCL_0455 | Lung mucoepidermoid carcinoma | Homo sapiens | |||
| In-vivo Model | A volume of 100 ul H23 cell suspension (1 * 108 cells/ml in normal saline) was subcutaneously injected into the right flanks of mouse (male BALB/c nude mice of 4-5 weeks old). | |||||
| Experimental
Result(s) |
Celastrol acts synergistically with afatinib to suppress non-small cell lung cancer cell proliferation by inducing paraptosis. | |||||
| β. A List of Natural Product(s) Able to Reverse the Resistance of This Drug | ||||||
| Bufalin | Bufo gargarizans | Click to Show/Hide the Molecular Data of This NP | ||||
| Reversing Drug Resistance | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [3] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | AKT1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CDH1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | EGFR | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | ERK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | MET | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | SNAI1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | VIM | Molecule Info |
Pathway MAP
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| In-vitro Model | NCI-H1975 | CVCL_1511 | Lung adenocarcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Bufalin reverses hepatocyte growth factor-induced resistance to afatinib in H1975 lung cancer cells. | |||||
| Target and Pathway | ||||
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| Target(s) | Epidermal growth factor receptor (EGFR) | Molecule Info | [4] | |
| Tyrosine kinase receptor Erbb2 (HER2) | Molecule Info | [4] | ||
| KEGG Pathway | ErbB signaling pathway | Click to Show/Hide | ||
| 2 | Calcium signaling pathway | |||
| 3 | HIF-1 signaling pathway | |||
| 4 | Focal adhesion | |||
| 5 | Adherens junction | |||
| 6 | Pathways in cancer | |||
| 7 | Proteoglycans in cancer | |||
| 8 | MicroRNAs in cancer | |||
| 9 | Pancreatic cancer | |||
| 10 | Endometrial cancer | |||
| 11 | Prostate cancer | |||
| 12 | Bladder cancer | |||
| 13 | Non-small cell lung cancer | |||
| 14 | Central carbon metabolism in cancer | |||
| 15 | MAPK signaling pathway | |||
| 16 | Ras signaling pathway | |||
| 17 | Rap1 signaling pathway | |||
| 18 | Cytokine-cytokine receptor interaction | |||
| 19 | FoxO signaling pathway | |||
| 20 | Endocytosis | |||
| 21 | PI3K-Akt signaling pathway | |||
| 22 | Dorso-ventral axis formation | |||
| 23 | Gap junction | |||
| 24 | Regulation of actin cytoskeleton | |||
| 25 | GnRH signaling pathway | |||
| 26 | Estrogen signaling pathway | |||
| 27 | Oxytocin signaling pathway | |||
| 28 | Epithelial cell signaling in Helicobacter pylori infection | |||
| 29 | Hepatitis C | |||
| 30 | Glioma | |||
| 31 | Melanoma | |||
| 32 | Choline metabolism in cancer | |||
| NetPath Pathway | TCR Signaling Pathway | Click to Show/Hide | ||
| 2 | IL4 Signaling Pathway | |||
| 3 | EGFR1 Signaling Pathway | |||
| Panther Pathway | Cadherin signaling pathway | Click to Show/Hide | ||
| 2 | EGF receptor signaling pathway | |||
| Pathwhiz Pathway | Phosphatidylinositol Phosphate Metabolism | Click to Show/Hide | ||
| Pathway Interaction Database | ErbB4 signaling events | Click to Show/Hide | ||
| 2 | ErbB2/ErbB3 signaling events | |||
| 3 | ErbB receptor signaling network | |||
| 4 | a6b1 and a6b4 Integrin signaling | |||
| 5 | Validated targets of C-MYC transcriptional repression | |||
| 6 | LPA receptor mediated events | |||
| 7 | Signaling events mediated by PTP1B | |||
| 8 | Arf6 signaling events | |||
| 9 | Signaling events mediated by TCPTP | |||
| 10 | Thromboxane A2 receptor signaling | |||
| 11 | SHP2 signaling | |||
| 12 | Regulation of Telomerase | |||
| 13 | EGF receptor (ErbB1) signaling pathway | |||
| 14 | EGFR-dependent Endothelin signaling events | |||
| 15 | Posttranslational regulation of adherens junction stability and dissassembly | |||
| 16 | Direct p53 effectors | |||
| 17 | ErbB1 downstream signaling | |||
| 18 | Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling | |||
| 19 | E-cadherin signaling in keratinocytes | |||
| 20 | Internalization of ErbB1 | |||
| 21 | Stabilization and expansion of the E-cadherin adherens junction | |||
| 22 | Syndecan-3-mediated signaling events | |||
| Reactome | SHC1 events in ERBB2 signaling | Click to Show/Hide | ||
| 2 | PLCG1 events in ERBB2 signaling | |||
| 3 | PIP3 activates AKT signaling | |||
| 4 | GRB2 events in ERBB2 signaling | |||
| 5 | PI3K events in ERBB2 signaling | |||
| 6 | Constitutive Signaling by Aberrant PI3K in Cancer | |||
| 7 | Sema4D induced cell migration and growth-cone collapse | |||
| 8 | RAF/MAP kinase cascade | |||
| 9 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | |||
| 10 | GRB2 events in EGFR signaling | |||
| 11 | GAB1 signalosome | |||
| 12 | SHC1 events in EGFR signaling | |||
| 13 | EGFR downregulation | |||
| 14 | EGFR Transactivation by Gastrin | |||
| 15 | Constitutive Signaling by EGFRvIII | |||
| WikiPathways | DNA Damage Response (only ATM dependent) | Click to Show/Hide | ||
| 2 | ErbB Signaling Pathway | |||
| 3 | EGF/EGFR Signaling Pathway | |||
| 4 | Focal Adhesion | |||
| 5 | Extracellular vesicle-mediated signaling in recipient cells | |||
| 6 | Bladder Cancer | |||
| 7 | Signaling by ERBB2 | |||
| 8 | Integrated Pancreatic Cancer Pathway | |||
| 9 | Signaling Pathways in Glioblastoma | |||
| 10 | Leptin signaling pathway | |||
| 11 | miR-targeted genes in muscle cell - TarBase | |||
| 12 | Semaphorin interactions | |||
| 13 | Regulation of Actin Cytoskeleton | |||
| 14 | MAPK Signaling Pathway | |||
| 15 | Aryl Hydrocarbon Receptor Pathway | |||
| 16 | TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer | |||
| 17 | Hair Follicle Development: Cytodifferentiation (Part 3 of 3) | |||
| 18 | Hair Follicle Development: Induction (Part 1 of 3) | |||
| 19 | Signaling by ERBB4 | |||
| 20 | Gastrin-CREB signalling pathway via PKC and MAPK | |||
| 21 | PIP3 activates AKT signaling | |||
| 22 | Nanoparticle-mediated activation of receptor signaling | |||
| 23 | Aryl Hydrocarbon Receptor | |||
| 24 | Spinal Cord Injury | |||
| 25 | Gastric cancer network 2 | |||
| 26 | AGE/RAGE pathway | |||
| 27 | Arylhydrocarbon receptor (AhR) signaling pathway | |||
| 28 | miR-targeted genes in lymphocytes - TarBase | |||
| 29 | miR-targeted genes in epithelium - TarBase | |||
| 30 | Integrated Breast Cancer Pathway | |||
| 31 | Signaling by EGFR | |||
| 32 | L1CAM interactions | |||
