Drug Details

General Information of the Drug (ID: DR2172)
Name
Afatinib
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
Disease Lung cancer [ICD-11: 2C25] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2-5 h
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability
Clearance
The total body clearance of drug is 1530 mL/min
Elimination
Following administration of an oral solution of 15 mg afatinib, 85.4% of the dose was recovered in the feces and 4.3% in urine
Half-life
The concentration or amount of drug in body reduced by one-half in 37 hours
Metabolism
The drug is metabolized via the enzyme-catalyzed metabolic reactions
Vd
The volume of distribution (Vd) of drug is 4500 L
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C24H25ClFN5O3
PubChem CID
10184653
Canonical SMILES
CN(C)CC=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OC4CCOC4
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
InChIKey
ULXXDDBFHOBEHA-CWDCEQMOSA-N
CAS Number
CAS 850140-72-6
ChEBI ID
CHEBI:61390
TTD Drug ID
D05UFG
DrugBank ID
DB08916
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    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
                    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
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression CDH1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation MET  Molecule Info 
Pathway MAP
Down-regulation Expression SNAI1  Molecule Info 
Pathway MAP
Down-regulation Expression VIM  Molecule Info 
Pathway MAP
                    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
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
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5667).
Reference 2 Celastrol acts synergistically with afatinib to suppress non-small cell lung cancer cell proliferation by inducing paraptosis. J Cell Physiol. 2021 Jun;236(6):4538-4554.
Reference 3 [Bufalin reverses hepatocyte growth factor-induced resistance to afatinib in H1975 lung cancer cells]. Zhonghua Zhong Liu Za Zhi. 2015 Jul;37(7):490-6.
Reference 4 Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
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