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

General Information of Drug (ID: DMZE2JO)

• Drug Name: SNS-595 Drug Info
• Synonyms: Voreloxin; Vosaroxin; AG 7352; SNS 595; SPC 595; AG 7352 (TN); AG-7352; SNS 595 (TN); SPC 595 (TN); SPC-595; Voreloxin (TN); Voreloxin (USAN); SNS-595 (TN); 1,4-Dihydro-7-(3-methoxy-4-methylamino-1-pyrrolidinyl)-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Phase 3	[1]
Ovarian cancer	2C73	Phase 2	[2]

• Cross-matching ID:
  PubChem CID: 9952884
  CAS Number: CAS 175414-77-4
  TTD Drug ID: DMZE2JO

Molecule-Related Drug Atlas

Drug(s) Targeting DNA topoisomerase II (TOP2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[5]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[6]
Teniposide	DMLW57T	Acute lymphoblastic leukaemia	2A85	Approved	[5]
Mitoxantrone	DMM39BF	Acute myelogenous leukaemia	2A41	Approved	[7]
Idarubicin	DMM0XGL	Acute myelogenous leukaemia	2A41	Approved	[5]
Epirubicin	DMPDW6T	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Lomefloxacin	DMVRH9C	Bacterial infection	1A00-1C4Z	Approved	[8]
Dexrazoxane	DMD7X1O	Breast cancer	2C60-2C65	Approved	[5]
Podofilox	DMT2EJP	Condyloma	1A95	Approved	[9]
Enoxacin	DMYTE6L	Acute gonococcal cervicitis		Approved	[10]

Drug(s) Affected By Superoxide dismutase , mitochondrial (SOD2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[11]
Selenium	DM25CGV	N. A.	N. A.	Approved	[12]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[14]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[15]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[16]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[17]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[18]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[19]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[20]

Drug(s) Affected By Isocitrate dehydrogenase , mitochondrial (IDH2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[21]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[22]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[23]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[24]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[25]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[26]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[27]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[28]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[29]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Isocitrate dehydrogenase , mitochondrial (IDH2)	OTTQA4PB	IDHP_HUMAN	Gene/Protein Processing	[4]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Gene/Protein Processing	[4]

References

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• [3] A phase 1b/2 study of vosaroxin in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia.Haematologica.2015 Feb;100(2):231-7.
• [4] Vosaroxin induces mitochondrial dysfunction and apoptosis in cervical cancer HeLa cells: Involvement of AMPK/Sirt3/HIF-1 pathway. Chem Biol Interact. 2018 Jun 25;290:57-63. doi: 10.1016/j.cbi.2018.05.011. Epub 2018 May 22.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
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• [7] Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6.
• [8] Inhibition of human topoisomerase IIalpha by fluoroquinolones and ultraviolet A irradiation. Toxicol Sci. 2002 Sep;69(1):16-22.
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• [11] Neuroprotective effects of glucomoringin-isothiocyanate against H(2)O(2)-Induced cytotoxicity in neuroblastoma (SH-SY5Y) cells. Neurotoxicology. 2019 Dec;75:89-104. doi: 10.1016/j.neuro.2019.09.008. Epub 2019 Sep 12.
• [12] Changes in gene expression profiles in response to selenium supplementation among individuals with arsenic-induced pre-malignant skin lesions. Toxicol Lett. 2007 Mar 8;169(2):162-76. doi: 10.1016/j.toxlet.2007.01.006. Epub 2007 Jan 19.
• [13] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [14] P450 3A-catalyzed O-dealkylation of lapatinib induces mitochondrial stress and activates Nrf2. Chem Res Toxicol. 2016 May 16;29(5):784-96.
• [15] Epinephrine upregulates superoxide dismutase in human coronary artery endothelial cells. Free Radic Biol Med. 2001 Jan 15;30(2):148-53.
• [16] Cissus quadrangularis ethanol extract upregulates superoxide dismutase, glutathione peroxidase and endothelial nitric oxide synthase expression in hydrogen peroxide-injured human ECV304 cells. J Ethnopharmacol. 2012 Sep 28;143(2):664-72.
• [17] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [18] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [19] Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma. Antioxid Redox Signal. 2014 May 20;20(15):2326-46. doi: 10.1089/ars.2013.5295. Epub 2013 Nov 14.
• [20] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [21] SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells. Antioxid Redox Signal. 2016 Feb 20;24(6):329-43. doi: 10.1089/ars.2015.6331. Epub 2015 Nov 10.
• [22] 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.
• [23] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [24] 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.
• [25] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [26] 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.
• [27] Novel roles of folic acid as redox regulator: Modulation of reactive oxygen species sinker protein expression and maintenance of mitochondrial redox homeostasis on hepatocellular carcinoma. Tumour Biol. 2017 Jun;39(6):1010428317702649. doi: 10.1177/1010428317702649.
• [28] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [29] 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.
• [30] Effects of paclitaxel on proliferation and apoptosis in human acute myeloid leukemia HL-60 cells. Acta Pharmacol Sin. 2004 Mar;25(3):378-84.