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
• DTT Type: Successful target; [1]
• 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.
• KEGG Pathway: Platinum drug resistance (hsa01524)
• 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

22 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aclarubicin	DMLFZHD	Acute myeloid leukaemia	2A60	Approved	[2]
Amsacrine	DMZKYIV	Acute lymphoblastic leukaemia	2A85	Approved	[1]
Cinoxacin	DM4EWNS	Urinary tract infection	GC08	Approved	[3]
Dexrazoxane	DMD7X1O	Breast cancer	2C60-2C65	Approved	[4]
Dhaq diacetate	DMU3FGB	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[4]
Enoxacin	DMYTE6L	Acute gonococcal cervicitis		Approved	[6]
Epirubicin	DMPDW6T	Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[7]
Fleroxacin	DMXGQYZ	Bacterial infection	1A00-1C4Z	Approved	[8]
Idarubicin	DMM0XGL	Acute myelogenous leukaemia	2A41	Approved	[4]
Lomefloxacin	DMVRH9C	Bacterial infection	1A00-1C4Z	Approved	[9]
Lucanthone	DMZLBUO	Solid tumour/cancer	2A00-2F9Z	Approved	[10]
Mitoxantrone	DMM39BF	Acute myelogenous leukaemia	2A41	Approved	[11]
Nalidixic Acid	DMRM0JV	Urinary tract infection	GC08	Approved	[12]
Novobiocin	DMRFWGK	Bacterial infection	1A00-1C4Z	Approved	[13]
Pefloxacin	DM49IGF	Gonococcal urethritis	1A70.0Y	Approved	[6]
Podofilox	DMT2EJP	Condyloma	1A95	Approved	[14]
Quinolones	DM5GVHU	Bacterial infection	1A00-1C4Z	Approved	[15]
Rosoxacin	DMVOIK1	Bacterial infection	1A00-1C4Z	Approved	[16]
Teniposide	DMLW57T	Acute lymphoblastic leukaemia	2A85	Approved	[4]
Valrubicin	DMOYJFK	Bladder cancer	2C94	Approved	[17]

27 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	[18]
GSK2140944	DMSMFN2	Neisseria gonorrhoeae infection	1A7Z	Phase 3	[19]
Pixantrone	DMQGR45	Diffuse large B-cell lymphoma	2A81	Phase 3	[18]
SNS-595	DMZE2JO	Acute myeloid leukaemia	2A60	Phase 3	[20]
Tirapazamine	DMBFE4K	Alzheimer disease	8A20	Phase 3	[18]
MTC-DOX	DMKMZW2	Liver cancer	2C12	Phase 2/3	[18]
13-DEOXYADRIAMYCIN HYDROCHLORIDE	DM4EP6Y	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
Berubicin	DMJ2REU	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
CAP-7.1	DMJKLHU	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
Doxorubicin-eluting beads	DM8VWPH	Liver cancer	2C12	Phase 2	[18]
Elsamitrucin	DMR50I7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[21]
GPX-150D	DMHNIGB	Breast cancer	2C60-2C65	Phase 2	[22]
PYRAZOLOACRIDINE	DMSOPAU	Colorectal cancer	2B91.Z	Phase 2	[23]
Sabarubicin	DMBZO8N	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
Salvicine	DM0298B	Solid tumour/cancer	2A00-2F9Z	Phase 2	[24]
XR-5000	DMOKUA5	Colorectal cancer	2B91.Z	Phase 2	[25]
F-14512	DML6EVJ	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[26]
L-377202	DMBEQ08	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[18]
AjvW2	DM6PN4H	Thrombosis	DB61-GB90	Phase 1	[27]
BMY-43748	DMW8VEH	Bacterial infection	1A00-1C4Z	Phase 1	[28]
Daniquidone	DMWT5RS	Lymphoma	2A80-2A86	Phase 1	[29]
GRC-6211	DMZ0D3V	Asthma	CA23	Phase 1	[12]
MLN-576	DMCVO2Y	Acute lymphoblastic leukaemia	2A85	Phase 1	[30]
NK-314	DMGSDPL	Solid tumour/cancer	2A00-2F9Z	Phase 1	[31]
Tafluposide	DMV8IQW	Solid tumour/cancer	2A00-2F9Z	Phase 1	[32]
TAS-103	DM5WDKY	Solid tumour/cancer	2A00-2F9Z	Phase 1	[33]
XR-5944	DMO9KZE	Gastric adenocarcinoma	2B72	Phase 1	[34]

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	[12]
BW-773U82	DMI2LFG	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[35]
ELINAFIDE MESILATE	DMBCYRG	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[36]
GL-331	DM10CBF	Colorectal cancer	2B91.Z	Discontinued in Phase 2	[37]
KW-2170	DM5YHJ2	Breast cancer	2C60-2C65	Discontinued in Phase 2	[38]
LOSOXANTRONE	DMM843E	Breast cancer	2C60-2C65	Discontinued in Phase 2	[39]
Merbarone	DMMZ4E9	Pancreatic cancer	2C10	Discontinued in Phase 2	[40]
Mitonafide	DMW59FE	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[41]
NC-190	DMGEBUQ	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[42]
SUPER-LEU-DOX	DM19Y0T	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[18]
Banoxantrone	DMK5I07	Acute lymphoblastic leukaemia	2A85	Discontinued in Phase 1	[18]
Teloxantrone	DMDT5HZ	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[43]
TOP-53	DMI0Q8Y	Metastatic lung cancer	2D70	Discontinued in Phase 1	[44]
A-62176	DM4WT7Z	N. A.	N. A.	Terminated	[46]
A-74932	DMNCGOP	Lung cancer	2C25.0	Terminated	[47]
BE-22179	DM39SEK	leukaemia	2A60-2B33	Terminated	[48]
Datelliptium chloride	DMR80AL	Breast cancer	2C60-2C65	Terminated	[49]
Doxorubicin-CEA conjugate	DM4BPFV	Breast cancer	2C60-2C65	Terminated	[4]
ER-37328	DMYSTAD	N. A.	N. A.	Terminated	[50]
Garenoxacin	DMZXA0W	Endocarditis	BB40-BA42	Terminated	[51]

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	[45]

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	[52]
1-Methoxy-3-(oxiran-2-ylmethoxy)-9H-xanthen-9-one	DMFVSBK	Discovery agent	N.A.	Investigative	[53]
2-(2-Aminoethyl)anthra[1,9-cd]pyrazol-6(2H)-one	DMDFYJR	Discovery agent	N.A.	Investigative	[54]
2-(2-Hydroxyethyl)anthra[1,9-cd]pyrazol-6(2H)-one	DMRPCL7	Discovery agent	N.A.	Investigative	[54]
3,3'-(4-phenylpyridine-2,6-diyl)diphenol	DMJVKMO	Discovery agent	N.A.	Investigative	[55]
3-(2,6-diphenylpyridin-4-yl)phenol	DMDYW4J	Discovery agent	N.A.	Investigative	[55]
3-(2-phenyl-6-(thiophen-2-yl)pyridin-4-yl)-phenol	DM63T9D	Discovery agent	N.A.	Investigative	[55]
3-(2-phenyl-6-(thiophen-3-yl)pyridin-4-yl)-phenol	DMF369N	Discovery agent	N.A.	Investigative	[55]
3-(4-phenyl-6-(thiophen-2-yl)pyridin-2-yl)-phenol	DM0OF64	Discovery agent	N.A.	Investigative	[55]
3-(4-phenyl-6-(thiophen-3-yl)pyridin-2-yl)-phenol	DMTR8SZ	Discovery agent	N.A.	Investigative	[55]
3-(6-(furan-2-yl)-4-phenylpyridin-2-yl)-phenol	DMADQCW	Discovery agent	N.A.	Investigative	[55]
4'-Demethyl-4beta-amino-4-desoxypodophyllotoxin	DMQWHLM	Discovery agent	N.A.	Investigative	[56]
4'-Demethyl-epipodophyllotoxin	DMIWX3B	Discovery agent	N.A.	Investigative	[56]
4,4'-(4-phenylpyridine-2,6-diyl)diphenol	DMJKWFI	Discovery agent	N.A.	Investigative	[55]
4-(furan-3-yl)-2,6-di(thiophen-2-yl)pyridine	DMW4O31	Discovery agent	N.A.	Investigative	[57]
7-chloro-1,3-dihydroxyacridone	DMPJWIB	Discovery agent	N.A.	Investigative	[52]
Ametantrone	DMDRSFE	Discovery agent	N.A.	Investigative	[58]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[59]
Clorobiocin	DMD5FIU	Discovery agent	N.A.	Investigative	[60]
DEMETHYLZEYLASTERONE	DMAMS7R	Discovery agent	N.A.	Investigative	[61]
doxorubicin-LL2 conjugate	DMNJBF8	Discovery agent	N.A.	Investigative	[62]
doxorubicin-peptide-PEG conjugate	DM2OCZ8	Discovery agent	N.A.	Investigative	[62]
Ellipticine	DMHPYSM	Discovery agent	N.A.	Investigative	[63]
Howiinol A (GHM-10)	DM2OZBL	Discovery agent	N.A.	Investigative	[64]
ICRF-154	DM9DXRL	Discovery agent	N.A.	Investigative	[27]
LUPEOL	DM4ZLUH	Discovery agent	N.A.	Investigative	[65]
Makaluvamine N	DMKE03Q	Discovery agent	N.A.	Investigative	[66]
Olean-12-en-3beta,15alpha-diol	DMVM78Q	Discovery agent	N.A.	Investigative	[65]
Pumiliotoxin 251D	DMY2F6T	Bacterial infection	1A00-1C4Z	Investigative	[67]
TOPOSTATIN	DMNZQO9	Discovery agent	N.A.	Investigative	[68]

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