Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMTKD7Q)

Drug Name

BIBW 2992 Drug Info

Synonyms

Afatinib; Tomtovok; Tovok; BIBW-2992; Tovok (TN); Tovok, BIBW2992; (2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[(3S)-tetrahydrofuran-3-yloxy]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide; EGFR inhibitor 2nd gens

Indication

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25.Y	Approved	[1]

Cross-matching ID

PubChem CID: 10184653
ChEBI ID: CHEMBL1173655
CAS Number: CAS 850140-72-6
TTD Drug ID: DMTKD7Q
VARIDT Drug ID: DR00354

Molecule-Related Drug Atlas

Molecule Type:

DTT

DTP

DOT

Drug Status:

Approved Drug(s)

Clinical Trial Drug(s)

Download the Complete Related Drug List

Drug(s) Targeting Erbb2 tyrosine kinase receptor (HER2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[7]
Dacomitinib	DMOH8VY	Non-small-cell lung cancer	2C25.Y	Approved	[8]
Merimepodib	DM0HS92	Breast cancer	2C60-2C65	Approved	[9]
NERATINIB MALEATE	DMEDU7B	HER2/NEU overexpressing breast cancer	2C60-2C65	Approved	[10]
Margetuximab	DMKEY6S	HER2-positive breast cancer	2C60-2C65	Approved	[11]
Trastuzumab	DMZQOUX	Breast cancer	2C60-2C65	Approved	[12]
Tucatinib	DMBESUA	HER2-positive breast cancer	2C60-2C65	Approved	[13]
Pertuzumab	DMHJV0X	Adrenal gland neoplasm		Approved	[14]
Masoprocol	DMMVNZ0	Prostate cancer	2C82.0	Approved	[15]
HKI-272	DM6QOVN	Breast cancer	2C60-2C65	Phase 3	[16]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Targeting Epidermal growth factor receptor (EGFR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[17]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[7]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[18]
Erlotinib	DMCMBHA	Adrenal gland neoplasm		Approved	[19]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[16]
Dacomitinib	DMOH8VY	Non-small-cell lung cancer	2C25.Y	Approved	[20]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[21]
Epidermal growth factor	DMVONE6	Vulnerary	ND56.Z	Approved	[20]
Merimepodib	DM0HS92	Breast cancer	2C60-2C65	Approved	[9]
Nitroglycerin	DMQ2491	Angina pectoris	BA40	Approved	[22]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[23]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[24]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[25]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[26]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[25]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[25]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[27]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[25]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[28]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[29]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Transported By Breast cancer resistance protein (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[30]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[31]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[32]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[33]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[34]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[35]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[36]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[35]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[37]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[38]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Affected By Ras GTPase-activating-like protein IQGAP1 (IQGAP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[39]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[40]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[6]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[41]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[42]
Dihydroartemisinin	DMBXVMZ	Malaria	1F40-1F45	Approved	[43]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[44]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[45]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[46]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[47]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Affected By Protein SET (SET)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[48]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[49]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[50]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[51]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[52]
Sevoflurane	DMC9O43	Anaesthesia	9A78.6	Approved	[52]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[53]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[45]
Diethylstilbestrol	DMN3UXQ	Gonorrheal vaginitis	GA02	Approved	[54]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[55]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Affected By POU domain, class 5, transcription factor 1 (POU5F1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[56]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[57]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[58]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[59]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[41]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[60]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[61]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[62]
Lamotrigine	DM8SXYG	Bipolar disorder	6A60	Approved	[63]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[64]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[2]
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Inhibitor	[2]

------------------------------------------------------------------------------------

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[3]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

------------------------------------------------------------------------------------

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
POU domain, class 5, transcription factor 1 (POU5F1)	OTDHHN7O	PO5F1_HUMAN	Gene/Protein Processing	[4]
Protein SET (SET)	OTGYYQJO	SET_HUMAN	Protein Interaction/Cellular Processes	[5]
Ras GTPase-activating-like protein IQGAP1 (IQGAP1)	OTZRWTGA	IQGA1_HUMAN	Post-Translational Modifications	[6]

------------------------------------------------------------------------------------

References

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).
2	Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
3	Breast cancer resistance protein (BCRP/ABCG2) and P-glycoprotein (P-gp/ABCB1) transport afatinib and restrict its oral availability and brain accumulation. Pharmacol Res. 2017 Jun;120:43-50.
4	YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells. PLoS One. 2017 Aug 7;12(8):e0182149. doi: 10.1371/journal.pone.0182149. eCollection 2017.
5	Oncoprotein SET dynamically regulates cellular stress response through nucleocytoplasmic transport in breast cancer. Cell Biol Toxicol. 2023 Aug;39(4):1795-1814. doi: 10.1007/s10565-022-09784-4. Epub 2022 Dec 19.
6	Tyrosine phosphorylation of the scaffold protein IQGAP1 in the MET pathway alters function. J Biol Chem. 2020 Dec 25;295(52):18105-18121. doi: 10.1074/jbc.RA120.015891. Epub 2020 Oct 21.
7	Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
8	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: 7422).
9	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
10	2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
11	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
12	Her2/neu is not a commonly expressed therapeutic target in melanoma -- a large cohort tissue microarray study. Melanoma Res. 2004 Jun;14(3):207-10.
13	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
14	Clinical pipeline report, company report or official report of Roche (2009).
15	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
16	A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
17	Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
18	Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer. 2004 Feb 9;90(3):566-72.
19	Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
20	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. (Target id: 1797).
21	Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
22	Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
23	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
24	MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
25	Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
26	Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
27	Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
28	Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
29	Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
30	Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
31	Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
32	The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
33	Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
34	Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
35	Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
36	The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
37	Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
38	Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
39	Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells. J Cell Biochem. 2006 Aug 1;98(5):1163-84.
40	Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
41	A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
42	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
43	Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells. Chem Res Toxicol. 2015 Oct 19;28(10):1903-13. doi: 10.1021/acs.chemrestox.5b00105. Epub 2015 Sep 21.
44	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
45	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
46	Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
47	Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
48	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
49	Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
50	Inhibition of fatty acid synthase expression by 1alpha,25-dihydroxyvitamin D3 in prostate cancer cells. J Steroid Biochem Mol Biol. 2003 May;85(1):1-8. doi: 10.1016/s0960-0760(03)00142-0.
51	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
52	The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence. Cell Biol Toxicol. 2023 Aug;39(4):1561-1575. doi: 10.1007/s10565-022-09747-9. Epub 2022 Aug 12.
53	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
54	Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
55	Synergistic effect of trichostatin A and 5-aza-2'-deoxycytidine on growth inhibition of pancreatic endocrine tumour cell lines: a proteomic study. Proteomics. 2009 Apr;9(7):1952-66. doi: 10.1002/pmic.200701089.
56	Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
57	Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism. Chem Biol Interact. 2016 Apr 25;250:1-11.
58	Quercetin in elimination of tumor initiating stem-like and mesenchymal transformation property in head and neck cancer. Head Neck. 2013 Mar;35(3):413-9. doi: 10.1002/hed.22982. Epub 2012 Mar 16.
59	Retinoic acid represses a cassette of candidate pluripotency chromosome 12p genes during induced loss of human embryonal carcinoma tumorigenicity. Biochim Biophys Acta. 2005 Oct 15;1731(1):48-56. doi: 10.1016/j.bbaexp.2005.08.006. Epub 2005 Sep 1.
60	The antipsychotic chlorpromazine suppresses YAP signaling, stemness properties, and drug resistance in breast cancer cells. Chem Biol Interact. 2019 Apr 1;302:28-35. doi: 10.1016/j.cbi.2019.01.033. Epub 2019 Jan 28.
61	Arsenic trioxide induces differentiation of cancer stem cells in hepatocellular carcinoma through inhibition of LIF/JAK1/STAT3 and NF-kB signaling pathways synergistically. Clin Transl Med. 2021 Feb;11(2):e335. doi: 10.1002/ctm2.335.
62	Altered expression of genes identified in rats with prostatic chronic inflammation in a prostate spheroid model treated by estradiol/testosterone. J Toxicol Sci. 2021;46(11):515-523. doi: 10.2131/jts.46.515.
63	Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
64	Effects of Exposure to Acetaminophen and Ibuprofen on Fetal Germ Cell Development in Both Sexes in Rodent and Human Using Multiple Experimental Systems. Environ Health Perspect. 2018 Apr 16;126(4):047006. doi: 10.1289/EHP2307.