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

General Information of Drug (ID: DMVYO41)

• Drug Name: XK-469 Drug Info
• Synonyms: Rac-2-[4-(7-Chloroquinoxalin-2-yloxy)phenoxy]propionic acid sodium salt

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 23675947
  CAS Number: CAS 157434-99-6
  TTD Drug ID: DMVYO41

Molecule-Related Drug Atlas

Drug(s) Targeting DNA topoisomerase II beta (TOP2B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dexrazoxane	DMD7X1O	Breast cancer	2C60-2C65	Approved	[5]
XB-947	DM1UIOA	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
A-62176	DM4WT7Z	N. A.	N. A.	Terminated	[7]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[8]
3'-THIO-THYMIDINE-5'-PHOSPHATE	DM5SM8X	Discovery agent	N.A.	Investigative	[8]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[9]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[10]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[11]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[12]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[13]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[14]
Floxuridine	DM04LR2	Colorectal cancer	2B91.Z	Approved	[15]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[16]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[17]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[18]

Drug(s) Affected By Cyclin-A2 (CCNA2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[19]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[20]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[21]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[23]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[24]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[25]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[26]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[27]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[28]

Drug(s) Affected By Aldehyde oxidase (AOX1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[29]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[28]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[30]
Methylprednisolone	DM4BDON	Acute adrenal insufficiency		Approved	[31]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[32]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[33]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[34]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[35]
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[36]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[37]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA topoisomerase II beta (TOP2B)	TT4NVEM	TOP2B_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aldehyde oxidase (AOX1)	OT2FZP6H	AOXA_HUMAN	Regulation of Drug Effects	[3]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[4]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Gene/Protein Processing	[4]

References

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• [3] In vitro-in vivo correlation for intrinsic clearance for drugs metabolized by human aldehyde oxidase. Drug Metab Dispos. 2010 Aug;38(8):1322-7. doi: 10.1124/dmd.110.033555. Epub 2010 May 5.
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• [6] XK469, a selective topoisomerase IIbeta poison. Proc Natl Acad Sci U S A. 1999 October 12; 96(21): 12168-12173.
• [7] Design of new topoisomerase II inhibitors based upon a quinobenzoxazine self-assembly model. J Med Chem. 1998 Oct 22;41(22):4273-8.
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• [19] 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.
• [20] G2 delay induced by nitrogen mustard in human cells affects cyclin A/cdk2 and cyclin B1/cdc2-kinase complexes differently. J Biol Chem. 1993 Apr 15;268(11):8298-308.
• [21] 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.
• [22] Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
• [23] Ribavirin inhibits colorectal cancer growth by downregulating PRMT5 expression and H3R8me2s and H4R3me2s accumulation. Toxicol Appl Pharmacol. 2021 Mar 15;415:115450. doi: 10.1016/j.taap.2021.115450. Epub 2021 Feb 9.
• [24] Sulindac induces specific degradation of the HPV oncoprotein E7 and causes growth arrest and apoptosis in cervical carcinoma cells. Cancer Lett. 2007 Jan 8;245(1-2):103-11. doi: 10.1016/j.canlet.2005.12.034. Epub 2006 Feb 20.
• [25] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [26] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [27] CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models. Genes Cancer. 2014 Jul;5(7-8):261-72. doi: 10.18632/genesandcancer.24.
• [28] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [29] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [30] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [31] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [32] Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
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• [34] 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.
• [35] 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.
• [36] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [37] 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.