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

General Information of Drug (ID: DMZQOUX)

• Drug Name: Trastuzumab Drug Info
• Synonyms: Herceptin; Herceptin (TN); Trastuzumab (INN); Trastuzumab (genetical recombination); Trastuzumab (genetical recombination) (JAN); Trastuzumab (ERBB2 mAb inhibitor)

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[1]
Inflammatory breast cancer	2C62	Approved	[2]
Lung cancer	2C25.0	Approved	[3]
Gastric adenocarcinoma	2B72	Application submitted	[4]
HER2-positive breast cancer	2C60-2C65	Application submitted	[4]
Gastric cancer	2B72	Investigative	[5]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  TTD Drug ID: DMZQOUX
  VARIDT Drug ID: DR01171

Molecule-Related Drug Atlas

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	[8]
Dacomitinib	DMOH8VY	Non-small-cell lung cancer	2C25.Y	Approved	[9]
BIBW 2992	DMTKD7Q	Non-small-cell lung cancer	2C25.Y	Approved	[10]
Merimepodib	DM0HS92	Breast cancer	2C60-2C65	Approved	[11]
NERATINIB MALEATE	DMEDU7B	HER2/NEU overexpressing breast cancer	2C60-2C65	Approved	[12]
Margetuximab	DMKEY6S	HER2-positive breast cancer	2C60-2C65	Approved	[13]
Tucatinib	DMBESUA	HER2-positive breast cancer	2C60-2C65	Approved	[14]
Pertuzumab	DMHJV0X	Adrenal gland neoplasm		Approved	[15]
Masoprocol	DMMVNZ0	Prostate cancer	2C82.0	Approved	[16]
HKI-272	DM6QOVN	Breast cancer	2C60-2C65	Phase 3	[17]

Drug(s) Affected By Receptor tyrosine-protein kinase erbB-2 (ERBB2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[18]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[19]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[20]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[21]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
Selenium	DM25CGV	N. A.	N. A.	Approved	[23]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[24]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[25]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[26]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Not Available	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Drug Response	[7]

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: 5082).
• [2] Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32.
• [3] Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2022 Jan 20;386(3):241-251.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730.
• [6] 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.
• [7] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [8] 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.
• [9] 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).
• [10] Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
• [11] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [12] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [15] Clinical pipeline report, company report or official report of Roche (2009).
• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [17] 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.
• [18] Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines. Cancers (Basel). 2020 Sep 27;12(10):2774. doi: 10.3390/cancers12102774.
• [19] Down-regulation of HER-2 expression in human breast cancer cell HBC-4 and ZR75-1 by nitrogen-mustard-N-oxide. Kobe J Med Sci. 2007;53(4):135-42.
• [20] Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol. 2004 Apr;32(2):397-414.
• [21] Epidermal growth factor receptor activity determines response of colorectal cancer cells to gefitinib alone and in combination with chemotherapy. Clin Cancer Res. 2005 Oct 15;11(20):7480-9. doi: 10.1158/1078-0432.CCR-05-0328.
• [22] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [23] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [24] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [25] Inhibition of prostate cancer cell colony formation by the flavonoid quercetin correlates with modulation of specific regulatory genes. Clin Diagn Lab Immunol. 2004 Jan;11(1):63-9. doi: 10.1128/cdli.11.1.63-69.2004.
• [26] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [27] Aspirin inhibits ErbB2 to induce apoptosis in cervical cancer cells. Med Oncol. 2010 Jun;27(2):379-87. doi: 10.1007/s12032-009-9221-0. Epub 2009 May 8.