Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT0IHXV)

• DTT Name: DNA topoisomerase II (TOP2)
• Synonyms: TOP2; DNA topoisomerase 2
• Gene Name: TOP2A; TOP2B
• DTT Type: Successful target; [1]
• Related Disease:
  Acute myeloid leukaemia [ICD-11: 2A60]
  Anogenital warts [ICD-11: 1A95]
  Bacterial infection [ICD-11: 1A00-1C4Z]
  Bladder cancer [ICD-11: 2C94]
  Breast cancer [ICD-11: 2C60-2C6Y]
  Chemoprotection [ICD-11: N.A.]
  Common warts [ICD-11: 1E80]
  Gonococcal infection [ICD-11: 1A70-1A7Z]
  HIV-infected patients with tuberculosis [ICD-11: 1B10-1B14]
  Mature B-cell lymphoma [ICD-11: 2A85]
  Otitis externa [ICD-11: AA00-AA13]
  Otitis media [ICD-11: AA80-AB0Z]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]
  Syphilis [ICD-11: 1A61-1A6Z]
  Urinary tract infection [ICD-11: GC08]
• BioChemical Class: ATP-hydrolyzing DNA topoisomerase
• UniProt ID: TOP2A_HUMAN ; TOP2B_HUMAN
• TTD ID: T96144
• Sequence:
  MEVSPLQPVNENMQVNKIKKNEDAKKRLSVERIYQKKTQLEHILLRPDTYIGSVELVTQQ
  MWVYDEDVGINYREVTFVPGLYKIFDEILVNAADNKQRDPKMSCIRVTIDPENNLISIWN
  NGKGIPVVEHKVEKMYVPALIFGQLLTSSNYDDDEKKVTGGRNGYGAKLCNIFSTKFTVE
  TASREYKKMFKQTWMDNMGRAGEMELKPFNGEDYTCITFQPDLSKFKMQSLDKDIVALMV
  RRAYDIAGSTKDVKVFLNGNKLPVKGFRSYVDMYLKDKLDETGNSLKVIHEQVNHRWEVC
  LTMSEKGFQQISFVNSIATSKGGRHVDYVADQIVTKLVDVVKKKNKGGVAVKAHQVKNHM
  WIFVNALIENPTFDSQTKENMTLQPKSFGSTCQLSEKFIKAAIGCGIVESILNWVKFKAQ
  VQLNKKCSAVKHNRIKGIPKLDDANDAGGRNSTECTLILTEGDSAKTLAVSGLGVVGRDK
  YGVFPLRGKILNVREASHKQIMENAEINNIIKIVGLQYKKNYEDEDSLKTLRYGKIMIMT
  DQDQDGSHIKGLLINFIHHNWPSLLRHRFLEEFITPIVKVSKNKQEMAFYSLPEFEEWKS
  STPNHKKWKVKYYKGLGTSTSKEAKEYFADMKRHRIQFKYSGPEDDAAISLAFSKKQIDD
  RKEWLTNFMEDRRQRKLLGLPEDYLYGQTTTYLTYNDFINKELILFSNSDNERSIPSMVD
  GLKPGQRKVLFTCFKRNDKREVKVAQLAGSVAEMSSYHHGEMSLMMTIINLAQNFVGSNN
  LNLLQPIGQFGTRLHGGKDSASPRYIFTMLSSLARLLFPPKDDHTLKFLYDDNQRVEPEW
  YIPIIPMVLINGAEGIGTGWSCKIPNFDVREIVNNIRRLMDGEEPLPMLPSYKNFKGTIE
  ELAPNQYVISGEVAILNSTTIEISELPVRTWTQTYKEQVLEPMLNGTEKTPPLITDYREY
  HTDTTVKFVVKMTEEKLAEAERVGLHKVFKLQTSLTCNSMVLFDHVGCLKKYDTVLDILR
  DFFELRLKYYGLRKEWLLGMLGAESAKLNNQARFILEKIDGKIIIENKPKKELIKVLIQR
  GYDSDPVKAWKEAQQKVPDEEENEESDNEKETEKSDSVTDSGPTFNYLLDMPLWYLTKEK
  KDELCRLRNEKEQELDTLKRKSPSDLWKEDLATFIEELEAVEAKEKQDEQVGLPGKGGKA
  KGKKTQMAEVLPSPRGQRVIPRITIEMKAEAEKKNKKKIKNENTEGSPQEDGVELEGLKQ
  RLEKKQKREPGTKTKKQTTLAFKPIKKGKKRNPWSDSESDRSSDESNFDVPPRETEPRRA
  ATKTKFTMDLDSDEDFSDFDEKTDDEDFVPSDASPPKTKTSPKLSNKELKPQKSVVSDLE
  ADDVKGSVPLSSSPPATHFPDETEITNPVPKKNVTVKKTAAKSQSSTSTTGAKKRAAPKG
  TKRDPALNSGVSQKPDPAKTKNRRKRKPSTSDDSDSNFEKIVSKAVTSKKSKGESDDFHM
  DFDSAVAPRAKSVRAKKPIKYLEESDEDDLF
• Function: Cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils.
• Reactome Pathway:
  SUMOylation of DNA replication proteins (R-HSA-4615885)
  Transcription of E2F targets under negative control by DREAM complex (R-HSA-1362277)

Molecular Interaction Atlas (MIA) of This DTT

23 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aclarubicin	DMLFZHD	Acute myeloid leukaemia	2A60	Approved	[2], [3]
Amsacrine	DMZKYIV	Acute lymphoblastic leukaemia	2A85	Approved	[1]
Cinoxacin	DM4EWNS	Urinary tract infection	GC08	Approved	[4]
Ciprofloxacin+dexamethasone	DMZR26N	Acute otitis media	AB00	Approved	[5]
Dexrazoxane	DMD7X1O	Breast cancer	2C60-2C65	Approved	[6]
Dhaq diacetate	DMU3FGB	Solid tumour/cancer	2A00-2F9Z	Approved	[7], [8]
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[6]
Enoxacin	DMYTE6L	Urinary tract infection	GC08	Approved	[9]
Epirubicin	DMPDW6T	Solid tumour/cancer	2A00-2F9Z	Approved	[6]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[10]
Fleroxacin	DMXGQYZ	Bacterial infection	1A00-1C4Z	Approved	[11]
Idarubicin	DMM0XGL	Acute myeloid leukaemia	2A60	Approved	[6]
Lomefloxacin	DMVRH9C	Bacterial infection	1A00-1C4Z	Approved	[12]
Lucanthone	DMZLBUO	Solid tumour/cancer	2A00-2F9Z	Approved	[13]
Mitoxantrone	DMM39BF	Solid tumour/cancer	2A00-2F9Z	Approved	[14]
Nalidixic acid	DMRM0JV	Urinary tract infection	GC08	Approved	[15]
Novobiocin	DMRFWGK	Bacterial infection	1A00-1C4Z	Approved	[16]
Pefloxacin	DM49IGF	Gonococcal urethritis	1A70.0Y	Approved	[9]
Podofilox	DMT2EJP	Condyloma	1A95	Approved	[17], [18]
Quinolones	DM5GVHU	Bacterial infection	1A00-1C4Z	Approved	[19]
Rosoxacin	DMVOIK1	Bacterial infection	1A00-1C4Z	Approved	[20]
Teniposide	DMLW57T	Acute lymphoblastic leukaemia	2A85	Approved	[6]
Valrubicin	DMOYJFK	Bladder cancer	2C94	Approved	[21]

28 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aldoxorubicin	DMHKCIS	Soft tissue sarcoma	2B57	Phase 3	[22]
GSK2140944	DMSMFN2	Neisseria gonorrhoeae infection	1A7Z	Phase 3	[23]
Pixantrone	DMQGR45	Diffuse large B-cell lymphoma	2A81	Phase 3	[22]
SNS-595	DMZE2JO	Acute myeloid leukaemia	2A60	Phase 3	[24]
Tirapazamine	DMBFE4K	Alzheimer disease	8A20	Phase 3	[22]
MTC-DOX	DMKMZW2	Liver cancer	2C12	Phase 2/3	[22]
13-DEOXYADRIAMYCIN HYDROCHLORIDE	DM4EP6Y	Solid tumour/cancer	2A00-2F9Z	Phase 2	[22]
Berubicin	DMJ2REU	Solid tumour/cancer	2A00-2F9Z	Phase 2	[22]
CAP-7.1	DMJKLHU	Solid tumour/cancer	2A00-2F9Z	Phase 2	[22]
Doxorubicin-eluting beads	DM8VWPH	Liver cancer	2C12	Phase 2	[22]
Elsamitrucin	DMR50I7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[25]
GPX-150D	DMHNIGB	Breast cancer	2C60-2C65	Phase 2	[26]
Pyrazoloacridine	DMSOPAU	Colorectal cancer	2B91.Z	Phase 2	[27]
Sabarubicin	DMBZO8N	Solid tumour/cancer	2A00-2F9Z	Phase 2	[22]
Salvicine	DM0298B	Solid tumour/cancer	2A00-2F9Z	Phase 2	[28], [29]
XR-5000	DMOKUA5	Colorectal cancer	2B91.Z	Phase 2	[30]
F-14512	DML6EVJ	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[31]
L-377202	DMBEQ08	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[22]
AjvW2	DM6PN4H	Thrombosis	DB61-GB90	Phase 1	[32]
BMY-43748	DMW8VEH	Bacterial infection	1A00-1C4Z	Phase 1	[33], [34]
Daniquidone	DMWT5RS	Lymphoma	2A80-2A86	Phase 1	[35]
GRC-6211	DMZ0D3V	Asthma	CA23	Phase 1	[15]
Iboctadekin + Doxil	DMW1ZAM	Ovarian cancer	2C73	Phase 1	[36]
MLN-576	DMCVO2Y	Acute lymphoblastic leukaemia	2A85	Phase 1	[37], [38]
NK-314	DMGSDPL	Solid tumour/cancer	2A00-2F9Z	Phase 1	[39]
Tafluposide	DMV8IQW	Solid tumour/cancer	2A00-2F9Z	Phase 1	[40]
TAS-103	DM5WDKY	Solid tumour/cancer	2A00-2F9Z	Phase 1	[41]
XR-5944	DMO9KZE	Gastric adenocarcinoma	2B72	Phase 1	[42]

20 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amifloxacin	DM4RFT8	N. A.	N. A.	Discontinued in Phase 2	[15]
BW-773U82	DMI2LFG	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[43]
ELINAFIDE MESILATE	DMBCYRG	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[44], [34]
GL-331	DM10CBF	Colorectal cancer	2B91.Z	Discontinued in Phase 2	[45], [46]
KW-2170	DM5YHJ2	Breast cancer	2C60-2C65	Discontinued in Phase 2	[47]
LOSOXANTRONE	DMM843E	Breast cancer	2C60-2C65	Discontinued in Phase 2	[48]
Merbarone	DMMZ4E9	Pancreatic cancer	2C10	Discontinued in Phase 2	[49]
Mitonafide	DMW59FE	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[50]
NC-190	DMGEBUQ	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[51], [52]
SUPER-LEU-DOX	DM19Y0T	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[22]
Banoxantrone	DMK5I07	Acute lymphoblastic leukaemia	2A85	Discontinued in Phase 1	[22]
Teloxantrone	DMDT5HZ	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[53]
TOP-53	DMI0Q8Y	Metastatic lung cancer	2D70	Discontinued in Phase 1	[54]
A-62176	DM4WT7Z	N. A.	N. A.	Terminated	[56]
A-74932	DMNCGOP	Lung cancer	2C25.0	Terminated	[57]
BE-22179	DM39SEK	leukaemia	2A60-2B33	Terminated	[58]
Datelliptium chloride	DMR80AL	Breast cancer	2C60-2C65	Terminated	[59]
Doxorubicin-CEA conjugate	DM4BPFV	Breast cancer	2C60-2C65	Terminated	[6]
ER-37328	DMYSTAD	N. A.	N. A.	Terminated	[60]
Garenoxacin	DMZXA0W	Endocarditis	BB40-BA42	Terminated	[61]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nemorubicin	DMX7Q3H	Solid tumour/cancer	2A00-2F9Z	Preclinical	[55]

30 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,3,7-trihydroxyacridone	DMFA8CW	Discovery agent	N.A.	Investigative	[3]
1-Methoxy-3-(oxiran-2-ylmethoxy)-9H-xanthen-9-one	DMFVSBK	Discovery agent	N.A.	Investigative	[62]
2-(2-Aminoethyl)anthra[1,9-cd]pyrazol-6(2H)-one	DMDFYJR	Discovery agent	N.A.	Investigative	[63]
2-(2-Hydroxyethyl)anthra[1,9-cd]pyrazol-6(2H)-one	DMRPCL7	Discovery agent	N.A.	Investigative	[63]
3,3'-(4-phenylpyridine-2,6-diyl)diphenol	DMJVKMO	Discovery agent	N.A.	Investigative	[64]
3-(2,6-diphenylpyridin-4-yl)phenol	DMDYW4J	Discovery agent	N.A.	Investigative	[64]
3-(2-phenyl-6-(thiophen-2-yl)pyridin-4-yl)-phenol	DM63T9D	Discovery agent	N.A.	Investigative	[64]
3-(2-phenyl-6-(thiophen-3-yl)pyridin-4-yl)-phenol	DMF369N	Discovery agent	N.A.	Investigative	[64]
3-(4-phenyl-6-(thiophen-2-yl)pyridin-2-yl)-phenol	DM0OF64	Discovery agent	N.A.	Investigative	[64]
3-(4-phenyl-6-(thiophen-3-yl)pyridin-2-yl)-phenol	DMTR8SZ	Discovery agent	N.A.	Investigative	[64]
3-(6-(furan-2-yl)-4-phenylpyridin-2-yl)-phenol	DMADQCW	Discovery agent	N.A.	Investigative	[64]
4'-Demethyl-4beta-amino-4-desoxypodophyllotoxin	DMQWHLM	Discovery agent	N.A.	Investigative	[65]
4'-Demethyl-epipodophyllotoxin	DMIWX3B	Discovery agent	N.A.	Investigative	[65]
4,4'-(4-phenylpyridine-2,6-diyl)diphenol	DMJKWFI	Discovery agent	N.A.	Investigative	[64]
4-(furan-3-yl)-2,6-di(thiophen-2-yl)pyridine	DMW4O31	Discovery agent	N.A.	Investigative	[66]
7-chloro-1,3-dihydroxyacridone	DMPJWIB	Discovery agent	N.A.	Investigative	[3]
Ametantrone	DMDRSFE	Discovery agent	N.A.	Investigative	[67]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[68]
Clorobiocin	DMD5FIU	Discovery agent	N.A.	Investigative	[69]
DEMETHYLZEYLASTERONE	DMAMS7R	Discovery agent	N.A.	Investigative	[70]
doxorubicin-LL2 conjugate	DMNJBF8	Discovery agent	N.A.	Investigative	[71]
doxorubicin-peptide-PEG conjugate	DM2OCZ8	Discovery agent	N.A.	Investigative	[71]
Ellipticine	DMHPYSM	Discovery agent	N.A.	Investigative	[72]
Howiinol A (GHM-10)	DM2OZBL	Discovery agent	N.A.	Investigative	[73]
ICRF-154	DM9DXRL	Discovery agent	N.A.	Investigative	[32]
LUPEOL	DM4ZLUH	Discovery agent	N.A.	Investigative	[74]
Makaluvamine N	DMKE03Q	Discovery agent	N.A.	Investigative	[75]
Olean-12-en-3beta,15alpha-diol	DMVM78Q	Discovery agent	N.A.	Investigative	[74]
Pumiliotoxin 251D	DMY2F6T	Bacterial infection	1A00-1C4Z	Investigative	[76]
TOPOSTATIN	DMNZQO9	Discovery agent	N.A.	Investigative	[77]

References

• [1] Design of two etoposide-amsacrine conjugates: topoisomerase II and tubuline polymerization inhibition and relation to cytotoxicity. Anticancer Drug Des. 2000 Dec;15(6):413-21.
• [2] Linker length in podophyllotoxin-acridine conjugates determines potency in vivo and in vitro as well as specificity against MDR cell lines. Anticancer Drug Des. 2001 Dec;16(6):305-15.
• [3] 1,3-Dihydroxyacridone derivatives as inhibitors of herpes virus replication. Antiviral Res. 2000 Feb;45(2):123-34.
• [4] The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7.
• [5] Emerging therapies for the treatment and prevention of otitis media. Expert Opin Emerg Drugs. 2006 May;11(2):251-64.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] The hypoxia-activated ProDrug AQ4N penetrates deeply in tumor tissues and complements the limited distribution of mitoxantrone. Cancer Res. 2009 Feb 1;69(3):940-7.
• [8] Topoisomerase II is required for mitoxantrone to signal nuclear factor kappa B activation in HL60 cells. J Biol Chem. 2000 Aug 18;275(33):25231-8.
• [9] Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet. 1988 Feb;14(2):96-121.
• [10] Etoposide, topoisomerase II and cancer.Curr Med Chem Anticancer Agents.2005 Jul;5(4):363-72.
• [11] Fleroxacin overview. Chemotherapy. 1996 Mar;42 Suppl 1:1-9.
• [12] Inhibition of human topoisomerase IIalpha by fluoroquinolones and ultraviolet A irradiation. Toxicol Sci. 2002 Sep;69(1):16-22.
• [13] Clonogenicity of human leukemic cells protected from cell-lethal agents by heat shock protein 70. Cell Stress Chaperones. 2005 Spring;10(1):37-45.
• [14] Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6.
• [15] Activity of fluoroquinolone antibiotics against Plasmodium falciparum in vitro. Antimicrob Agents Chemother. 1988 Aug;32(8):1182-6.
• [16] Transcriptional responses of Bacillus subtillis and thuringiensis to antibiotics and anti-tumour drugs. Int J Mol Med. 2009 Jan;23(1):33-9.
• [17] Antitumor properties of podophyllotoxin and related compounds. Curr Pharm Des. 2000 Dec;6(18):1811-39.
• [18] Identification of therapeutic candidates for chronic lymphocytic leukemia from a library of approved drugs.PLoS One.2013 Sep 20;8(9):e75252.
• [19] The magic bullets and tuberculosis drug targets. Annu Rev Pharmacol Toxicol. 2005;45:529-64.
• [20] Inhibition of Micrococcus luteus DNA gyrase by norfloxacin and 10 other quinolone carboxylic acids. Antimicrob Agents Chemother. 1986 Apr;29(4):598-601.
• [21] Metabolic activation of N-acylanthracyclines precedes their interaction with DNA topoisomerase II. NCI Monogr. 1987;(4):111-5.
• [22] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [23] Determination of disk diffusion and MIC quality control guidelines for GSK2140944, a novel bacterial type II topoisomerase inhibitor antimicrobial agent. J Clin Microbiol. 2014 Jul;52(7):2629-32.
• [24] 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.
• [25] Elsamicin A binding to DNA. A comparative thermodynamic characterization. FEBS Lett. 2004 Oct 8;576(1-2):68-72.
• [26] Company report (Gem pharmaceuticals)
• [27] Effect of pyrazoloacridine (NSC 366140) on DNA topoisomerases I and II. Clin Cancer Res. 1998 Mar;4(3):683-91.
• [28] Salvicine, a novel topoisomerase II inhibitor, exerts its potent anticancer activity by ROS generation. Acta Pharmacol Sin. 2007 Sep;28(9):1460-5.
• [29] Salvicine functions as novel topoisomerase II poison by binding to ATP pocket. Mol Pharmacol. 2006 Nov;70(5):1593-601.
• [30] Phase II study of XR5000 (DACA) administered as a 120-h infusion in patients with recurrent glioblastoma multiforme. Ann Oncol. 2002 May;13(5):777-80.
• [31] Regulation by survivin of cancer cell death induced by F14512, a polyamine-containing inhibitor of DNA topoisomerase II.Apoptosis.2012 Apr;17(4):364-76.
• [32] The catalytic DNA topoisomerase II inhibitor ICRF-193 and all-trans retinoic acid cooperatively induce granulocytic differentiation of acute promyelocytic leukemia cells: candidate drugs for chemo-differentiation therapy against acute promyelocytic leukemia. Exp Hematol. 2002 Nov;30(11):1273-82.
• [33] Comparative metabolism of tosufloxacin and BMY 43748 in hepatocytes from rat, dog, monkey and man. Toxicol In Vitro. 1993 Jul;7(4):499-503.
• [34] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [35] Pharmacogenetically driven patient selection for a first-in-human phase I trial of batracylin in patients with advanced solid tumors and lymphomas.Cancer Chemother Pharmacol.2013 Oct;72(4):917-23.
• [36] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [37] In vitro and in vivo characterization of XR11576, a novel, orally active, dual inhibitor of topoisomerase I and II. Anticancer Drugs. 2002 Jan;13(1):15-28.
• [38] Ex vivo characterization of XR11576 (MLN576) against ovarian cancer and other solid tumors. Anticancer Drugs. 2004 Oct;15(9):849-60.
• [39] NK314, a topoisomerase II inhibitor that specifically targets the alpha isoform. J Biol Chem. 2008 Aug 29;283(35):23711-20.
• [40] Ex vivo effects of the dual topoisomerase inhibitor tafluposide (F 11782) on cells isolated from fresh tumor samples taken from patients with cancer. Anticancer Drugs. 2003 Jul;14(6):467-73.
• [41] Mechanism of action of the dual topoisomerase-I and -II inhibitor TAS-103 and activity against (multi)drug resistant cells. Cancer Chemother Pharmacol. 2000;45(1):78-84.
• [42] Antitumor activity of XR5944, a novel and potent topoisomerase poison. Anticancer Drugs. 2001 Apr;12(4):359-67.
• [43] Correlation of cytotoxicity and protein-associated DNA strand breaks for 2-(arylmethylamino)-1,3-propanediols. Anticancer Drug Des. 1998 Oct;13(7):825-35.
• [44] Solution structure and dynamics of a complex between DNA and the antitumor bisnaphthalimide LU-79553: intercalated ring flipping on the millisecond time scale. Biochemistry. 1999 Nov 16;38(46):15104-15.
• [45] GL331, a topoisomerase II inhibitor, induces radiosensitization of human glioma cells. Anticancer Res. 2006 May-Jun;26(3A):2149-56.
• [46] Induction of apoptosis and cell cycle arrest in glioma cells by GL331 (a topoisomerase II inhibitor). Anticancer Res. 2005 Nov-Dec;25(6B):4203-8.
• [47] KW-2170 (Kyowa Hakko Kogyo). IDrugs. 2002 Oct;5(10):1000-3.
• [48] A structure-based 3D-QSAR study of anthrapyrazole analogues of the anticancer agents losoxantrone and piroxantrone. J Chem Inf Model. 2006 Jul-Aug;46(4):1827-35.
• [49] The DNA topoisomerase II catalytic inhibitor merbarone is genotoxic and induces endoreduplication. Mutat Res. 2012 Oct-Nov;738-739:45-51.
• [50] Effect of mitonafide analogs on topoisomerase II of Leishmania chagasi. Antimicrob Agents Chemother. 1996 Mar;40(3):706-9.
• [51] The topoisomerase II-inhibitor NC-190 reduces the level of thymidine kinase mRNA in murine tumor cells. Res Commun Mol Pathol Pharmacol. 2002;111(1-4):77-87.
• [52] A novel antitumor compound, NC-190, induces topoisomerase II-dependent DNA cleavage and DNA fragmentation. Cancer Chemother Pharmacol. 1996;38(1):29-34.
• [53] Topoisomerase II inhibition and cytotoxicity of the anthrapyrazoles DuP 937 and DuP 941 (Losoxantrone) in the National Cancer Institute preclinical... J Natl Cancer Inst. 1994 Aug 17;86(16):1239-44.
• [54] DNA topoisomerase II as the target for the anticancer drug TOP-53: mechanistic basis for drug action. Biochemistry. 2001 Jan 23;40(3):712-8.
• [55] The interaction of nemorubicin metabolite PNU-159682 with DNA fragments d(CGTACG)(2), d(CGATCG)(2) and d(CGCGCG)(2) shows a strong but reversible binding to G:C base pairs. Bioorg Med Chem. 2012 Dec 15;20(24):6979-88.
• [56] Design of new topoisomerase II inhibitors based upon a quinobenzoxazine self-assembly model. J Med Chem. 1998 Oct 22;41(22):4273-8.
• [57] Use of catalytic topoisomerase II inhibitors to probe mechanisms of chemical-induced clastogenicity in Chinese hamster V79 cells. Environ Mol Mutagen. 2000;35(1):13-21.
• [58] A new topoisomerase II inhibitor, BE-22179, produced by a streptomycete. I. Producing strain, fermentation, isolation and biological activity. J Antibiot (Tokyo). 1994 Feb;47(2):129-35.
• [59] Toxicity of the antitumoral drug datelliptium in hepatic cells: Use of models in vitro for the prediction of toxicity in vivo. Toxicol In Vitro. 1992 Jul;6(4):295-302.
• [60] Antitumor activity of ER-37328, a novel carbazole topoisomerase II inhibitor. Mol Cancer Ther. 2002 Jan;1(3):169-75.
• [61] The inhibition and selectivity of bacterial topoisomerases by BMS-284756 and its analogues. J Antimicrob Chemother. 2001 Aug;48(2):195-201.
• [62] Synthesis and pharmacological evaluation of new methyloxiranylmethoxyxanthone analogues. Eur J Med Chem. 2010 Sep;45(9):4221-8.
• [63] Design, synthesis and biological evaluation of a novel series of anthrapyrazoles linked with netropsin-like oligopyrrole carboxamides as anticancer... Bioorg Med Chem. 2010 Jun 1;18(11):3974-84.
• [64] Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of hydroxylated 2,4-diphenyl-6-aryl ... Bioorg Med Chem. 2010 May 1;18(9):3066-77.
• [65] Antitumor agents, 107. New cytotoxic 4-alkylamino analogues of 4'-demethyl-epipodophyllotoxin as inhibitors of human DNA topoisomerase II. J Nat Prod. 1989 May-Jun;52(3):606-13.
• [66] 2,6-Dithienyl-4-furyl pyridines: Synthesis, topoisomerase I and II inhibition, cytotoxicity, structure-activity relationship, and docking study. Bioorg Med Chem Lett. 2010 Jan 1;20(1):42-7.
• [67] Interactions of antitumor agents Ametantrone and Mitoxantrone (Novatrone) with double-stranded DNA. Biochem Pharmacol. 1985 Dec 15;34(24):4203-13.
• [68] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [69] The high-resolution crystal structure of a 24-kDa gyrase B fragment from E.coli complexed with one of the most potent coumarin inhibitors, clorobiocin. Proteins. 1997 May;28(1):41-52.
• [70] Catalytic inhibition of topoisomerase IIalpha by demethylzeylasterone, a 6-oxophenolic triterpenoid from Kokoona zeylanica. J Nat Prod. 2001 Oct;64(10):1294-6.
• [71] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [72] In vitro sensitivity of Trichomonas vaginalis to DNA topoisomerase II inhibitors. Southeast Asian J Trop Med Public Health. 2000 Mar;31(1):118-22.
• [73] Anticancer effect of Howiinol A and its mechanism of action. J Asian Nat Prod Res. 1999;2(1):1-19.
• [74] Screening of triterpenoids isolated from Phyllanthus flexuosus for DNA topoisomerase inhibitory activity. J Nat Prod. 2001 Dec;64(12):1545-7.
• [75] Makaluvamine N: a new pyrroloiminoquinone from Zyzzya fuliginosa. J Nat Prod. 1997 Apr;60(4):408-10.
• [76] How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
• [77] Isoaurostatin, a novel topoisomerase inhibitor produced by Thermomonospora alba. J Nat Prod. 2001 Feb;64(2):204-7.