Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6LPS08)

• DOT Name: DNA topoisomerase 2-alpha (TOP2A)
• Synonyms: EC 5.6.2.2; DNA topoisomerase II, alpha isozyme
• Gene Name: TOP2A
• UniProt ID: TOP2A_HUMAN
• PDB ID: 1ZXM; 1ZXN; 4FM9; 4R1F; 5GWK; 5NNE; 6ZY5; 6ZY6; 6ZY7; 6ZY8
• EC Number: 5.6.2.2
• Pfam ID: PF00204 ; PF00521 ; PF08070 ; PF02518 ; PF01751 ; PF16898
• 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: Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. May play a role in regulating the period length of BMAL1 transcriptional oscillation.
• Tissue Specificity: Expressed in the tonsil, spleen, lymph node, thymus, skin, pancreas, testis, colon, kidney, liver, brain and lung . Also found in high-grade lymphomas, squamous cell lung tumors and seminomas .
• 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 DOT

This DOT Affected the Drug Response of 7 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	DNA topoisomerase 2-alpha (TOP2A) decreases the response to substance of Etoposide.	[76]
Paclitaxel	DMLB81S	Approved	DNA topoisomerase 2-alpha (TOP2A) increases the response to substance of Paclitaxel.	[77]
Vinblastine	DM5TVS3	Approved	DNA topoisomerase 2-alpha (TOP2A) affects the response to substance of Vinblastine.	[78]
Amsacrine	DMZKYIV	Approved	DNA topoisomerase 2-alpha (TOP2A) decreases the response to substance of Amsacrine.	[76]
Teniposide	DMLW57T	Approved	DNA topoisomerase 2-alpha (TOP2A) increases the Cytogenetic abnormality ADR of Teniposide.	[80]
Berberine	DMC5Q8X	Phase 4	DNA topoisomerase 2-alpha (TOP2A) affects the response to substance of Berberine.	[81]
5,11-Dimethyl-6H-pyrido[4,3-b]carbazol-9-ol	DMWSLTB	Investigative	DNA topoisomerase 2-alpha (TOP2A) affects the response to substance of 5,11-Dimethyl-6H-pyrido[4,3-b]carbazol-9-ol.	[37]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Adenosine triphosphate	DM79F6G	Approved	DNA topoisomerase 2-alpha (TOP2A) increases the hydrolysis of Adenosine triphosphate.	[79]

78 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of DNA topoisomerase 2-alpha (TOP2A).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of DNA topoisomerase 2-alpha (TOP2A).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of DNA topoisomerase 2-alpha (TOP2A).	[16]
Marinol	DM70IK5	Approved	Marinol increases the expression of DNA topoisomerase 2-alpha (TOP2A).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[18]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[19]
Menadione	DMSJDTY	Approved	Menadione affects the expression of DNA topoisomerase 2-alpha (TOP2A).	[20]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[5]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of DNA topoisomerase 2-alpha (TOP2A).	[21]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of DNA topoisomerase 2-alpha (TOP2A).	[22]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[23]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[25]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[26]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[27]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[28]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[29]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[30]
Menthol	DMG2KW7	Approved	Menthol increases the expression of DNA topoisomerase 2-alpha (TOP2A).	[31]
Topotecan	DMP6G8T	Approved	Topotecan decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[32]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[33]
Methamphetamine	DMPM4SK	Approved	Methamphetamine decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[34]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[35]
Tetracycline	DMZA017	Approved	Tetracycline decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[37]
Lapatinib	DM3BH1Y	Approved	Lapatinib decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[38]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[39]
Dronedarone	DMA8FS5	Approved	Dronedarone decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[40]
Dexrazoxane	DMD7X1O	Approved	Dexrazoxane decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[41]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[42]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[43]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of DNA topoisomerase 2-alpha (TOP2A).	[3]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of DNA topoisomerase 2-alpha (TOP2A).	[44]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[45]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of DNA topoisomerase 2-alpha (TOP2A).	[8]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone affects the activity of DNA topoisomerase 2-alpha (TOP2A).	[46]
URSOLIC ACID	DM4SOAW	Phase 2	URSOLIC ACID decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[47]
Delphinidin	DMS2WIN	Phase 2	Delphinidin decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[49]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[50]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[51]
TAK-114	DMTXE19	Phase 1	TAK-114 decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[53]
BETULINIC ACID	DMBUI2A	Phase 1	BETULINIC ACID decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[54]
PJ34	DMXO6YH	Preclinical	PJ34 increases the expression of DNA topoisomerase 2-alpha (TOP2A).	[56]
EMODIN	DMAEDQG	Terminated	EMODIN increases the activity of DNA topoisomerase 2-alpha (TOP2A).	[57]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[58]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of DNA topoisomerase 2-alpha (TOP2A).	[59]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[60]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[62]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[63]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[64]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[65]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[66]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[67]
Rutin	DMEHRAJ	Investigative	Rutin decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[68]
CATECHIN	DMY38SB	Investigative	CATECHIN decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[68]
NAPQI	DM8F5LR	Investigative	NAPQI decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[69]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone increases the expression of DNA topoisomerase 2-alpha (TOP2A).	[70]
Myricetin	DMTV4L0	Investigative	Myricetin decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[71]
OLEANOLIC_ACID	DMWDMJ3	Investigative	OLEANOLIC_ACID decreases the expression of DNA topoisomerase 2-alpha (TOP2A).	[72]
GW7604	DMCA4RM	Investigative	GW7604 increases the expression of DNA topoisomerase 2-alpha (TOP2A).	[21]
1,2-NAPHTHOQUINONE	DMYXELH	Investigative	1,2-NAPHTHOQUINONE affects the activity of DNA topoisomerase 2-alpha (TOP2A).	[73]
3-acetyl-11-keto-beta-boswellic acid	DMGO2D7	Investigative	3-acetyl-11-keto-beta-boswellic acid decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[47]
Formic Acid	DMNFZC6	Investigative	Formic Acid decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[74]
ALTENUSIN	DMYCS0B	Investigative	ALTENUSIN decreases the activity of DNA topoisomerase 2-alpha (TOP2A).	[75]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Niclosamide	DMJAGXQ	Approved	Niclosamide affects the binding of DNA topoisomerase 2-alpha (TOP2A).	[24]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR affects the binding of DNA topoisomerase 2-alpha (TOP2A).	[36]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of DNA topoisomerase 2-alpha (TOP2A).	[52]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of DNA topoisomerase 2-alpha (TOP2A).	[55]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of DNA topoisomerase 2-alpha (TOP2A).	[55]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid affects the phosphorylation of DNA topoisomerase 2-alpha (TOP2A).	[61]

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