Target Information
| Target General Information | Top | |||||
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| Target ID |
T85733
(Former ID: TTDR01192)
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| Target Name |
DNA topoisomerase II beta (TOP2B)
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| Synonyms |
Topo IIbeta; TOP2beta; TOP2B
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| Gene Name |
TOP2B
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Breast cancer [ICD-11: 2C60-2C6Y] | |||||
| 2 | Chemoprotection [ICD-11: N.A.] | |||||
| Function |
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.
Click to Show/Hide
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| BioChemical Class |
ATP-hydrolyzing DNA topoisomerase
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| UniProt ID | ||||||
| EC Number |
EC 5.6.2.3
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| 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 Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Dexrazoxane | Drug Info | Approved | Breast cancer | [2], [3] | |
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | XB-947 | Drug Info | Phase 1 | Solid tumour/cancer | [4] | |
| 2 | XK-469 | Drug Info | Phase 1 | Solid tumour/cancer | [5] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 4 Inhibitor drugs | + | ||||
| 1 | Dexrazoxane | Drug Info | [1] | |||
| 2 | A-62176 | Drug Info | [8] | |||
| 3 | 3'-THIO-THYMIDINE-5'-PHOSPHATE | Drug Info | [9] | |||
| 4 | AMP-PNP | Drug Info | [9] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | XB-947 | Drug Info | [6] | |||
| 2 | XK-469 | Drug Info | [7] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | DNA replication | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7330). | |||||
| REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076068. | |||||
| REF 4 | A phase I and pharmacokinetic study of the quinoxaline antitumour Agent R(+)XK469 in patients with advanced solid tumours. Eur J Cancer. 2008 August; 44(12): 1684-1692. | |||||
| REF 5 | ClinicalTrials.gov (NCT00028522) R(+)XK469 in Treating Patients With Advanced Neuroblastoma. U.S. National Institutes of Health. | |||||
| REF 6 | XK469, a selective topoisomerase IIbeta poison. Proc Natl Acad Sci U S A. 1999 October 12; 96(21): 12168-12173. | |||||
| REF 7 | A pharmacogenetic study of aldehyde oxidase I in patients treated with XK469.Pharmacogenet Genomics.2014 Feb;24(2):129-32. | |||||
| REF 8 | Design of new topoisomerase II inhibitors based upon a quinobenzoxazine self-assembly model. J Med Chem. 1998 Oct 22;41(22):4273-8. | |||||
| REF 9 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
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