Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT4NVEM)

• DTT Name: DNA topoisomerase II beta (TOP2B)
• Synonyms: Topo IIbeta; TOP2beta; TOP2B
• Gene Name: TOP2B
• DTT Type: Successful target; [1]
• BioChemical Class: ATP-hydrolyzing DNA topoisomerase
• UniProt ID: TOP2B_HUMAN
• TTD ID: T85733
• EC Number: EC 5.6.2.3
• Sequence:
  MAKSGGCGAGAGVGGGNGALTWVTLFDQNNAAKKEESETANKNDSSKKLSVERVYQKKTQ
  LEHILLRPDTYIGSVEPLTQFMWVYDEDVGMNCREVTFVPGLYKIFDEILVNAADNKQRD
  KNMTCIKVSIDPESNIISIWNNGKGIPVVEHKVEKVYVPALIFGQLLTSSNYDDDEKKVT
  GGRNGYGAKLCNIFSTKFTVETACKEYKHSFKQTWMNNMMKTSEAKIKHFDGEDYTCITF
  QPDLSKFKMEKLDKDIVALMTRRAYDLAGSCRGVKVMFNGKKLPVNGFRSYVDLYVKDKL
  DETGVALKVIHELANERWDVCLTLSEKGFQQISFVNSIATTKGGRHVDYVVDQVVGKLIE
  VVKKKNKAGVSVKPFQVKNHIWVFINCLIENPTFDSQTKENMTLQPKSFGSKCQLSEKFF
  KAASNCGIVESILNWVKFKAQTQLNKKCSSVKYSKIKGIPKLDDANDAGGKHSLECTLIL
  TEGDSAKSLAVSGLGVIGRDRYGVFPLRGKILNVREASHKQIMENAEINNIIKIVGLQYK
  KSYDDAESLKTLRYGKIMIMTDQDQDGSHIKGLLINFIHHNWPSLLKHGFLEEFITPIVK
  ASKNKQELSFYSIPEFDEWKKHIENQKAWKIKYYKGLGTSTAKEAKEYFADMERHRILFR
  YAGPEDDAAITLAFSKKKIDDRKEWLTNFMEDRRQRRLHGLPEQFLYGTATKHLTYNDFI
  NKELILFSNSDNERSIPSLVDGFKPGQRKVLFTCFKRNDKREVKVAQLAGSVAEMSAYHH
  GEQALMMTIVNLAQNFVGSNNINLLQPIGQFGTRLHGGKDAASPRYIFTMLSTLARLLFP
  AVDDNLLKFLYDDNQRVEPEWYIPIIPMVLINGAEGIGTGWACKLPNYDAREIVNNVRRM
  LDGLDPHPMLPNYKNFKGTIQELGQNQYAVSGEIFVVDRNTVEITELPVRTWTQVYKEQV
  LEPMLNGTDKTPALISDYKEYHTDTTVKFVVKMTEEKLAQAEAAGLHKVFKLQTTLTCNS
  MVLFDHMGCLKKYETVQDILKEFFDLRLSYYGLRKEWLVGMLGAESTKLNNQARFILEKI
  QGKITIENRSKKDLIQMLVQRGYESDPVKAWKEAQEKAAEEDETQNQHDDSSSDSGTPSG
  PDFNYILNMSLWSLTKEKVEELIKQRDAKGREVNDLKRKSPSDLWKEDLAAFVEELDKVE
  SQEREDVLAGMSGKAIKGKVGKPKVKKLQLEETMPSPYGRRIIPEITAMKADASKKLLKK
  KKGDLDTAAVKVEFDEEFSGAPVEGAGEEALTPSVPINKGPKPKREKKEPGTRVRKTPTS
  SGKPSAKKVKKRNPWSDDESKSESDLEETEPVVIPRDSLLRRAAAERPKYTFDFSEEEDD
  DADDDDDDNNDLEELKVKASPITNDGEDEFVPSDGLDKDEYTFSPGKSKATPEKSLHDKK
  SQDFGNLFSFPSYSQKSEDDSAKFDSNEEDSASVFSPSFGLKQTDKVPSKTVAAKKGKPS
  SDTVPKPKRAPKQKKVVEAVNSDSDSEFGIPKKTTTPKGKGRGAKKRKASGSENEGDYNP
  GRKTSKTTSKKPKKTSFDQDSDVDIFPSDFPTEPPSLPRTGRARKEVKYFAESDEEEDDV
  DFAMFN
• Function: Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.
• KEGG Pathway: Platinum drug resistance (hsa01524)
• Reactome Pathway: SUMOylation of DNA replication proteins (R-HSA-4615885)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dexrazoxane	DMD7X1O	Breast cancer	2C60-2C65	Approved	[1]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
XB-947	DM1UIOA	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
XK-469	DMVYO41	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-62176	DM4WT7Z	N. A.	N. A.	Terminated	[4]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3'-THIO-THYMIDINE-5'-PHOSPHATE	DM5SM8X	Discovery agent	N.A.	Investigative	[5]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[5]

References

• [1] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [2] XK469, a selective topoisomerase IIbeta poison. Proc Natl Acad Sci U S A. 1999 October 12; 96(21): 12168-12173.
• [3] A pharmacogenetic study of aldehyde oxidase I in patients treated with XK469.Pharmacogenet Genomics.2014 Feb;24(2):129-32.
• [4] Design of new topoisomerase II inhibitors based upon a quinobenzoxazine self-assembly model. J Med Chem. 1998 Oct 22;41(22):4273-8.
• [5] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.