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

General Information of Drug (ID: DMYNPK8)

• Drug Name: Hexylcarbamoyl fluorouracil Drug Info
• Synonyms: Carmofur; HCFU; Yamaful; 1-hexylcarbamoyl-5-fluorouracil

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Withdrawn from market	[1]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[2]

• Cross-matching ID:
  PubChem CID: 2577
  ChEBI ID: CHEBI:31360
  CAS Number: CAS 61422-45-5
  TTD Drug ID: DMYNPK8

Molecule-Related Drug Atlas

Drug(s) Targeting COVID-19 papain-like proteinase (PL-PRO)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Disulfiram	DMCL2OK	Alcohol dependence	6C40.2	Approved	[2]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[4]
SPI-1005	DM6XFHS	Reperfusion injury	ND56.Z	Approved	[2]
PX-12	DMLVHAJ	Pancreatic cancer	2C10	Phase 2	[2]
Tideglusib	DME4LA1	Alzheimer disease	8A20	Phase 2	[2]
PMID26868298-compound-N3	DMQFUCD	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[2]
GRL0617	DMX9AGF	Coronavirus infection	1D92	Preclinical	[5]
Isoarnebin 4	DM0B7NO	Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[2]
PMID32321856-compound-11a	DMN39V6	Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[6]
PMID32321856-compound-11b	DM31QEY	Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[6]

Drug(s) Affected By Cellular tumor antigen p53 (TP53)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[7]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[8]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[9]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[10]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[11]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[12]
Floxuridine	DM04LR2	Colorectal cancer	2B91.Z	Approved	[13]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[14]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[15]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[16]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
COVID-19 papain-like proteinase (PL-PRO)	TTNHMO8	R1AB_SARS2 (819-2763)	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[3]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Structure of Mpro from COVID-19 virus and discovery of its inhibitors. Nature. 2020 Apr 9.
• [3] Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
• [4] ClinicalTrials.gov (NCT04361422) Isotretinoin in Treatment of COVID-19. U.S. National Institutes of Health.
• [5] Crystal structure of SARS-CoV-2 papain-like protease. Acta Pharm Sin B. 2021 Jan;11(1):237-245.
• [6] Structure-based Design of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease. Science. 2020 Apr 22;eabb4489.
• [7] p53-R175H mutant gains new function in regulation of doxorubicin-induced apoptosis. Int J Cancer. 2005 Apr 10;114(3):331-6. doi: 10.1002/ijc.20818.
• [8] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [9] Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line. Toxicol Appl Pharmacol. 2006 Oct 1;216(1):89-97. doi: 10.1016/j.taap.2006.04.015. Epub 2006 May 19.
• [10] Quantitative analysis of gene expression changes in response to genotoxic compounds. Toxicol In Vitro. 2017 Mar;39:15-28. doi: 10.1016/j.tiv.2016.11.004. Epub 2016 Nov 5.
• [11] Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
• [12] Gallic acid potentiates the apoptotic effect of paclitaxel and carboplatin via overexpression of Bax and P53 on the MCF-7 human breast cancer cell line. J Biochem Mol Toxicol. 2021 Feb;35(2):e22638. doi: 10.1002/jbt.22638. Epub 2020 Oct 1.
• [13] Regulation of human dUTPase gene expression and p53-mediated transcriptional repression in response to oxaliplatin-induced DNA damage. Nucleic Acids Res. 2009 Jan;37(1):78-95. doi: 10.1093/nar/gkn910. Epub 2008 Nov 16.
• [14] Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
• [15] Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes. Chem Res Toxicol. 2022 Apr 18;35(4):636-650. doi: 10.1021/acs.chemrestox.1c00420. Epub 2022 Mar 21.
• [16] Fulvestrant induces resistance by modulating GPER and CDK6 expression: implication of methyltransferases, deacetylases and the hSWI/SNF chromatin remodelling complex. Br J Cancer. 2013 Nov 12;109(10):2751-62. doi: 10.1038/bjc.2013.583. Epub 2013 Oct 29.