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

General Information of Drug (ID: DML6GAN)

• Drug Name: Taxol/Paraplatin/Herceptin Drug Info
• Synonyms: Paclitaxel/carboplatin/trastuzumab

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 3	[1]

• Cross-matching ID: TTD Drug ID: DML6GAN

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	[3]
Dacomitinib	DMOH8VY	Non-small-cell lung cancer	2C25.Y	Approved	[4]
BIBW 2992	DMTKD7Q	Non-small-cell lung cancer	2C25.Y	Approved	[5]
Merimepodib	DM0HS92	Breast cancer	2C60-2C65	Approved	[6]
NERATINIB MALEATE	DMEDU7B	HER2/NEU overexpressing breast cancer	2C60-2C65	Approved	[7]
Margetuximab	DMKEY6S	HER2-positive breast cancer	2C60-2C65	Approved	[8]
Trastuzumab	DMZQOUX	Breast cancer	2C60-2C65	Approved	[9]
Tucatinib	DMBESUA	HER2-positive breast cancer	2C60-2C65	Approved	[10]
Pertuzumab	DMHJV0X	Adrenal gland neoplasm		Approved	[11]
Masoprocol	DMMVNZ0	Prostate cancer	2C82.0	Approved	[12]

Drug(s) Targeting Apoptosis regulator Bcl-2 (BCL-2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MCI-186	DM8ZHP1	Amyotrophic lateral sclerosis	8B60.0	Approved	[13]
Taxol	DMUOT9V	Breast cancer	2C60-2C65	Approved	[14]
GDC-0199	DMH0QKA	Chronic lymphocytic leukaemia	2A82.0	Approved	[15]
ABT-263	DMNE56X	Myelofibrosis	2A20.2	Phase 3	[11]
Oblimersen	DM7KI4E	Melanoma	2C30	Phase 3	[16]
RG7601	DMDVAFP	Chronic lymphocytic leukaemia	2A82.0	Phase 3	[15]
Thymoquinone	DMVDTR2	Polycystic ovarian syndrome	5A80.1	Phase 2/3	[17]
Obatoclax	DMPF9ZM	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
PI-88/Taxotere	DM4FIWC	Solid tumour/cancer	2A00-2F9Z	Phase 2	[19]
Gossypol	DMJWE3I	Prostate cancer	2C82.0	Phase 2	[20]

Drug(s) Targeting Human Deoxyribonucleic acid (hDNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[21]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[22]
Daunorubicin	DMQUSBT	Acute monocytic leukemia		Approved	[23]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[24]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[25]
Carboplatin	DMG281S	Adenocarcinoma	2D40	Approved	[26]
Busulfan	DMXYJ9C	Chronic myelogenous leukaemia	2A20.0	Approved	[27]
Procarbazine	DMIK367	Hodgkin lymphoma	2B30	Approved	[28]
Dactinomycin	DM2YGNW	Adult kidney Wilms tumor		Approved	[29]
Dacarbazine	DMNPZL4	Adenocarcinoma	2D40	Approved	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Apoptosis regulator Bcl-2 (BCL-2)	TTJGNVC	BCL2_HUMAN	Modulator	[2]
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Inhibitor	[2]
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Binder	[1]

References

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• [2] Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005 Dec;6(5):425-32.
• [3] 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.
• [4] 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).
• [5] Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
• [6] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [7] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [9] 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.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [11] Clinical pipeline report, company report or official report of Roche (2009).
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [13] Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
• [14] Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
• [15] ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8.
• [16] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [17] Apoptosis as a mechanism for the treatment of adult T cell leukemia: promising drugs from benchside to bedside. Drug Discov Today. 2020 Jul;25(7):1189-1197.
• [18] Phase II study of obatoclax mesylate (GX15-070), a small-molecule BCL-2 family antagonist, for patients with myelofibrosis. Clin Lymphoma Myeloma Leuk. 2010 Aug;10(4):285-9.
• [19] Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer. Ann Oncol. 2010 Jun;21(6):1302-7.
• [20] Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
• [21] Cisplatin and DNA repair in cancer chemotherapy.Trends Biochem Sci.1995 Oct;20(10):435-9.
• [22] Structures of oxaliplatin-oligonucleotide adducts from DNA.J Mass Spectrom.2012 Oct;47(10):1282-93.
• [23] 31P NMR spectra of ethidium, quinacrine, and daunomycin complexes with poly(adenylic acid).poly(uridylic acid) RNA duplex and calf thymus DNA. Biochemistry. 1989 Apr 4;28(7):2804-12.
• [24] Pharmacokinetics and metabolism of ifosfamide in relation to DNA damage assessed by the COMET assay in children with cancer. Br J Cancer. 2005 May 9;92(9):1626-35.
• [25] O6-methylguanine-DNA methyltransferase activity and sensitivity to cyclophosphamide and cisplatin in human lung tumor xenografts. Int J Cancer. 1998 Sep 11;77(6):919-22.
• [26] Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer.Clin Cancer Res.2010 Oct 1;16(19):4899-905.
• [27] DNA intrastrand cross-link at the 5'-GA-3' sequence formed by busulfan and its role in the cytotoxic effect. Cancer Sci. 2004 May;95(5):454-8.
• [28] Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O(6)-methylguanine triggered apoptosis, DSBs and chromosomal aberrations... DNA Repair (Amst). 2009 Jan 1;8(1):72-86.
• [29] Structural studies of atom-specific anticancer drugs acting on DNA. Pharmacol Ther. 1999 Sep;83(3):181-215.
• [30] Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mono... Melanoma Res. 2011 Dec;21(6):502-8.