TOP2A

Summary

TOP2A (DNA topoisomerase II alpha, HGNC:11989) is a protein-coding gene on chromosome 17q21.2, encoding DNA topoisomerase 2-alpha (P11388). 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. In precision oncology, TOP2A EXPRESSION confers sensitivity to Doxorubicin in Breast Cancer (CIViC Level B). It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).

This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another, thus altering the topology of DNA. Two forms of this enzyme exist as likely products of a gene duplication event. The gene encoding this form, alpha, is localized to chromosome 17 and the beta gene is localized to chromosome 3. The gene encoding this enzyme functions as the target for several anticancer agents and a variety of mutations in this gene have been associated with the development of drug resistance. Reduced activity of this enzyme may also play a role in ataxia-telangiectasia.

Source: NCBI Gene 7153 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 162 total
• Regional missense constraint (gnomAD): 4 of 10 regions constrained (≈5% of expected missense variation)
• GTEx eGene: eQTL in 5 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 9 curated mechanism-of-action drugs, 8 via a complex or family; 19 molecules with ChEMBL bioactivity (top 2% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 6 — Daunorubicin, Doxorubicin Hydrochloride, Etoposide Phosphate, +3 more
• Approved drugs acting on a complex or family including it: 3 — Amsacrine, Dexrazoxane, Teniposide (DNA topoisomerase II)
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.42 (moderately constrained)
• MANE Select transcript: NM_001067
• Interaction hub: 5,129 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11989
Approved symbol	TOP2A
Name	DNA topoisomerase II alpha
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	TOP2alpha, TOPIIA
Ensembl gene	ENSG00000131747
Ensembl biotype	protein_coding
OMIM	126430
Entrez	7153

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000423485

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 4: 1

ENST00000423485, ENST00000577541, ENST00000577706, ENST00000578412, ENST00000581055, ENST00000917864, ENST00000917865, ENST00001060014, ENST00001060015, ENST00001060016, ENST00001060017

RefSeq mRNA: 1 — MANE Select: NM_001067 NM_001067

CCDS: CCDS45672

Canonical transcript exons

ENST00000423485 — 35 exons

Exon	Start	End
ENSE00000900568	40392585	40392737
ENSE00000900569	40395449	40395539
ENSE00000900570	40396283	40396465
ENSE00000900573	40399040	40399131
ENSE00000900574	40399872	40400067
ENSE00000900575	40400209	40400409
ENSE00000900576	40400529	40400663
ENSE00000900577	40400850	40401081
ENSE00000900578	40402906	40403054
ENSE00000900579	40404152	40404273
ENSE00000900580	40404377	40404491
ENSE00000900581	40404791	40404883
ENSE00000900583	40406584	40406689
ENSE00000900584	40406832	40406942
ENSE00000900588	40407967	40408124
ENSE00000900590	40408492	40408630
ENSE00000900596	40411109	40411246
ENSE00001182061	40391506	40391640
ENSE00001182144	40412759	40412971
ENSE00001182163	40416005	40416068
ENSE00001182168	40416422	40416512
ENSE00001363882	40411645	40411818
ENSE00001368747	40411354	40411455
ENSE00001533405	40392068	40392111
ENSE00001533409	40392218	40392341
ENSE00001533480	40413195	40413292
ENSE00001594286	40407549	40407674
ENSE00001633936	40406384	40406493
ENSE00001750547	40388525	40389647
ENSE00001780806	40417771	40417896
ENSE00003459573	40389965	40390164
ENSE00003507255	40416740	40416895
ENSE00003526356	40398773	40398937
ENSE00003664321	40398558	40398641
ENSE00003788736	40413480	40413625

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 99.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.3822 / max 2345.5880, expressed in 1592 samples.

Highest expression (Bgee): ventricular zone, ganglionic eminence, secondary oocyte, embryo, testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TOP2A is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 5 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

5 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Hippocampus	eqtl	1.1e-02	-0.62	17:40305388:T:C
Colon Sigmoid	eqtl	1.1e-02	-0.48	17:39857107:G:A
Esophagus Gastroesophageal Junction	eqtl	2.4e-02	+0.79	17:40811809:T:A
Nerve Tibial	eqtl	2.6e-02	-0.20	17:39455099:C:T
Skin Sun Exposed Lower leg	eqtl	3.8e-02	+0.06	17:40907692:T:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
165716	68.6659	1578
165717	3.1792	878
165710	0.3398	24
165714	0.1972	95

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.62	gold quality
ganglionic eminence	UBERON:0004023	98.94	gold quality
secondary oocyte	CL:0000655	98.82	gold quality
embryo	UBERON:0000922	98.54	gold quality
right testis	UBERON:0004534	95.39	gold quality
oocyte	CL:0000023	95.26	gold quality
left testis	UBERON:0004533	94.51	gold quality
bone marrow	UBERON:0002371	93.80	gold quality
trabecular bone tissue	UBERON:0002483	93.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.68	gold quality
testis	UBERON:0000473	93.67	gold quality
bone marrow cell	CL:0002092	93.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.58	gold quality
endometrium epithelium	UBERON:0004811	91.44	gold quality
stromal cell of endometrium	CL:0002255	91.41	gold quality
thymus	UBERON:0002370	91.30	gold quality
mucosa of transverse colon	UBERON:0004991	91.07	gold quality
lower esophagus mucosa	UBERON:0035834	90.88	gold quality
oral cavity	UBERON:0000167	90.39	gold quality
adrenal tissue	UBERON:0018303	90.00	gold quality
vermiform appendix	UBERON:0001154	88.96	gold quality
gingival epithelium	UBERON:0001949	88.51	gold quality
rectum	UBERON:0001052	88.19	gold quality
gingiva	UBERON:0001828	87.95	gold quality
pylorus	UBERON:0001166	87.94	gold quality
sperm	CL:0000019	86.78	gold quality
esophagus squamous epithelium	UBERON:0006920	86.78	gold quality
esophagus mucosa	UBERON:0002469	86.59	gold quality
male germ cell	CL:0000015	86.43	gold quality
caecum	UBERON:0001153	86.34	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.31	gold quality
squamous epithelium	UBERON:0006914	86.02	gold quality
colonic mucosa	UBERON:0000317	85.72	gold quality
epithelium of nasopharynx	UBERON:0001951	85.69	gold quality
epithelium of esophagus	UBERON:0001976	85.35	gold quality
duodenum	UBERON:0002114	85.10	gold quality
pharyngeal mucosa	UBERON:0000355	84.66	gold quality
lymph node	UBERON:0000029	84.42	gold quality
jejunal mucosa	UBERON:0000399	84.36	gold quality
cartilage tissue	UBERON:0002418	84.04	gold quality
hair follicle	UBERON:0002073	83.51	gold quality
colonic epithelium	UBERON:0000397	83.49	gold quality
endometrium	UBERON:0001295	83.12	gold quality
tonsil	UBERON:0002372	83.00	gold quality
adult organism	UBERON:0007023	82.26	gold quality
amniotic fluid	UBERON:0000173	82.03	gold quality
tibia	UBERON:0000979	81.97	gold quality
cervix squamous epithelium	UBERON:0006922	81.29	gold quality
cervix epithelium	UBERON:0004801	81.21	gold quality
placenta	UBERON:0001987	81.16	gold quality
tongue squamous epithelium	UBERON:0006919	79.72	gold quality
oviduct epithelium	UBERON:0004804	78.05	gold quality
cortical plate	UBERON:0005343	77.83	gold quality
transverse colon	UBERON:0001157	76.57	gold quality
skin of abdomen	UBERON:0001416	75.96	gold quality
small intestine	UBERON:0002108	75.93	gold quality
smooth muscle tissue	UBERON:0001135	75.89	gold quality
zone of skin	UBERON:0000014	75.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.26	gold quality
spleen	UBERON:0002106	74.85	gold quality
superior surface of tongue	UBERON:0007371	74.76	gold quality
skin of leg	UBERON:0001511	74.71	gold quality
intestine	UBERON:0000160	74.66	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.59	gold quality
large intestine	UBERON:0000059	73.70	gold quality
mammalian vulva	UBERON:0000997	73.56	gold quality
tendon of biceps brachii	UBERON:0008188	73.54	gold quality
colon	UBERON:0001155	73.02	gold quality
penis	UBERON:0000989	72.39	gold quality
jejunum	UBERON:0002115	72.39	gold quality
esophagus	UBERON:0001043	72.35	gold quality
vagina	UBERON:0000996	72.23	gold quality
gall bladder	UBERON:0002110	71.93	gold quality
monocyte	CL:0000576	71.39	gold quality
mononuclear cell	CL:0000842	71.06	gold quality
leukocyte	CL:0000738	70.69	gold quality
visceral pleura	UBERON:0002401	70.28	gold quality
upper leg skin	UBERON:0004262	70.08	gold quality
stomach	UBERON:0000945	69.91	gold quality
tongue	UBERON:0001723	69.63	gold quality
uterus	UBERON:0000995	69.51	gold quality
right coronary artery	UBERON:0001625	69.11	gold quality
pleura	UBERON:0000977	68.96	gold quality
upper arm skin	UBERON:0004263	68.78	silver quality
parietal pleura	UBERON:0002400	68.70	gold quality
body of stomach	UBERON:0001161	68.39	gold quality
islet of Langerhans	UBERON:0000006	68.01	gold quality
female reproductive system	UBERON:0000474	68.01	gold quality
mouth mucosa	UBERON:0003729	67.93	gold quality
fallopian tube	UBERON:0003889	67.93	gold quality
nasal cavity mucosa	UBERON:0001826	67.67	gold quality
decidua	UBERON:0002450	67.59	silver quality
skin of hip	UBERON:0001554	67.57	gold quality
right adrenal gland	UBERON:0001233	67.32	gold quality
lung	UBERON:0002048	67.31	gold quality
right adrenal gland cortex	UBERON:0035827	67.21	gold quality
palpebral conjunctiva	UBERON:0001812	66.97	gold quality
upper lobe of lung	UBERON:0008948	66.93	gold quality
uterine cervix	UBERON:0000002	66.72	gold quality
superficial temporal artery	UBERON:0001614	66.52	gold quality

Single-cell (SCXA)

Detected in 54 experiment(s), a significant marker in 48.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	5407.73
E-MTAB-6819	yes	3364.02
E-GEOD-93593	yes	2856.31
E-MTAB-8894	yes	2778.54
E-MTAB-11121	yes	2730.22
E-MTAB-6379	yes	2111.64
E-HCAD-56	yes	1810.73
E-GEOD-98556	yes	1799.00
E-MTAB-10485	yes	1685.22
E-MTAB-10662	yes	1572.91
E-ENAD-17	yes	1550.14
E-CURD-79	yes	1470.90
E-HCAD-31	yes	1418.31
E-ENAD-20	yes	1318.32
E-GEOD-124858	yes	1259.54

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	119.0
Testis	tissue	56.3	high
Tonsil	tissue	39.8	high
Bone marrow	tissue	39.6	high
Lymph node	tissue	37.6	high
Appendix	tissue	18.8	medium
Rectum	tissue	18.5	medium
Duodenum	tissue	17.1	medium
Colon	tissue	16.7	medium
Small intestine	tissue	16.0	medium
Placenta	tissue	15.0	high
Skin 1	tissue	14.4	high
Esophagus	tissue	10.3	medium
Vagina	tissue	9.3	medium
Stomach 1	tissue	8.4	medium
Smooth muscle	tissue	7.1	not detected
Spleen	tissue	5.8	medium
Urinary bladder	tissue	5.7	medium
Breast	tissue	5.0	low
Caudate putamen	tissue	4.2
Ovary	tissue	4.0	not detected
Endometrium 1	tissue	3.6	medium
Cervix	tissue	2.8	medium
Basal ganglia	tissue	2.7	not detected
Gallbladder	tissue	2.4	low
Choroid plexus	tissue	2.3
Liver	tissue	2.2	not detected
Adipose tissue	tissue	2.1	not detected
Lung	tissue	2.1	low
Thyroid gland	tissue	1.8	not detected
Spinal cord	tissue	1.7
Corpus callosum	tissue	1.4
Fallopian tube	tissue	1.4	low
Prostate	tissue	1.2	medium
Septum	tissue	1.2
Substantia nigra	tissue	1.1
Hippocampal formation	tissue	1.1
Frontal cortex	tissue	1.0
Amygdala	tissue	1.0
Salivary gland	tissue	0.9	not detected
Hypothalamus	tissue	0.9
Olfactory bulb	tissue	0.9
Pons	tissue	0.8
Putamen	tissue	0.8
Midbrain	tissue	0.8
Thalamus	tissue	0.8
Adrenal gland	tissue	0.8	low
Ventral forebrain	tissue	0.8
Medulla oblongata	tissue	0.7
Superior colliculi	tissue	0.6
Kidney	tissue	0.6	not detected
Prefrontal cortex	tissue	0.5
Cerebral cortex	tissue	0.5	not detected
Periaqueductal gray	tissue	0.5
Retrosplenial cortex	tissue	0.5
Heart muscle	tissue	0.4	not detected
Seminal vesicle	tissue	0.4	low
Entorhinal cortex	tissue	0.4
Retrosplenial and cingulate cortex	tissue	0.4
Temporal cortex	tissue	0.4

Brain sub-regions (HPA Brain Atlas): detected in 115; highest nTPM — Anterior thalamic nucleus, ventral (2.3), Dorsal spinal cord (1.7), Blood vessel (1.6), Pedunculopontine tegmental nucleus (1.6), Ventral spinal cord (1.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF1, CEBPA, E2F1, E2F4, NFYB, UHRF1, YBX1

miRNA regulators (miRDB)

Targeting TOP2A by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 65 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-548A-3P	99.76	70.58	3524

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.422, missense Z 5 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000423485 splits into 10 regions with different missense tolerance; 4 are missense-constrained (≈5% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
17:40,389,522–40,396,443	374 / 403.3	0.93	no
17:40,396,444–40,398,600	4 / 22.6	0.18	yes (p 9.1e-05)
17:40,398,601–40,398,794	22 / 21.1	1.04	no
17:40,398,795–40,398,847	3 / 20.3	0.15	yes (p 1.2e-04)
17:40,398,848–40,400,911	232 / 306.1	0.76	no
17:40,400,912–40,406,902	209 / 376.9	0.55	no
17:40,406,903–40,407,559	0 / 20.1	0.00	yes (p 7.4e-06)
17:40,407,560–40,413,255	252 / 434.8	0.58	no
17:40,413,256–40,413,525	3 / 32.6	0.09	yes (p 2.2e-07)
17:40,413,526–40,417,791	97 / 171.0	0.57	no
DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): HT-29 (-4.265), GAMG (-3.8), U-251 MG (-3.798), SF767 (-3.728), LS1034 (-3.701), EC-GI-10 (-3.676), TC-71 (-3.648), NCI-H1944 (-3.626), SUP-M2 (-3.581), SNU-620 (-3.551), EBC-1 (-3.545), HUP-T3 (-3.535), PK-1 (-3.507), KALS-1 (-3.506), Hs 683 (-3.469).

Literature-anchored findings (GeneRIF, showing 40)

• The heat-induced transition of TOP2A requires both Mg2+ and DNA, is stable for several hours and leads to loss of DNA strand activity. A second transition correlates with a drop in the level of DNA scission, followed by religation at high temperatures. (PMID:11444988)
• increased expression appears to be part of malignant cells’ phenotype in recurrent colon cancers (PMID:11862483)
• topo II is not an immobile, structural component of the chromosomal scaffold or the interphase karyoskeleton, but rather a dynamic interaction partner of such structures. (PMID:11927602)
• The role of topoisomerase II in the excision of DNA loop domains during apoptosis. (PMID:11940566)
• Topoisomerase II alpha represents a reliable alternative to monoclonal antibody MIB-1 as a proliferation marker in human meningiomas. (PMID:11958416)
• Overexpression of topoisomerase IIalpha induced by mutant p53 is associated with aggressive carcinogenesis in non-small cell lung carcinoma (PMID:12001123)
• Transcriptional regulation of the human topoisomerase IIalpha gene (PMID:12014628)
• Redox control of cell cycle-coupled topoisomerase II alpha gene expression (PMID:12078518)
• The ATP-operated clamp of human DNA topoisomerase IIalpha: model for DNA-dependent ATPase activity. (PMID:12079377)
• presence of dna topoisomerase II in different testicular tumor types (PMID:12237772)
• Co-localizes with centromere activity and proteins within a subdomain of the major human X chromosome array (PMID:12356743)
• Topoisomerase II-alpha expression in rectal epithelium has a significant circadian variation and giving topoisomerase II-targeted chemotherapeutic agents at the proper time of day might reduce their mucositis side effects. (PMID:12429798)
• Topo IIalpha may provide crucial information regarding selection of adenohypophyseal tumors responsive to antineoplastic therapy, such as invasive pituitary adenomas and pituitary carcinomas, which exhibit a high Topo IIalpha index. (PMID:12429800)
• promoter elements responsible for transcriptional inhibition of polo-like kinase 1 and topoisomerase IIalpha genes by p21(WAF1/CIP1/SDI1) (PMID:12429910)
• A heterodimer of this protein with only one ATP binding site can go through successive catalytic cycles (PMID:12480934)
• Phosphorylation of serine 1106 in the catalytic domain of this enzyme regulates enzymatic activity and drug sensitivity. (PMID:12569090)
• Thr792 in human TOP2 alpha is involved in enzyme catalysis (PMID:12646164)
• Analysis of TOP2A gene amplification and gene overexpression in newly diagnosed childhood ALL cases and inverse correlation with glucocorticoid resistance (PMID:12646941)
• induction of topoisomerase IIalpha expression by peroxisome proliferator-activated receptor gamma ligands via DR1-like site is an important mechanism for the enhancement of etoposide-induced apoptosis (PMID:12691917)
• topoisomerase II is actively exported from the nuclease and is mediated by a CRM1-dependent pathway (PMID:12821127)
• Results suggest that topo IIalpha-depleted cells with the droplet-like nuclear structure induce apoptosis, which is dependent on caspase and p53 activity during the G1 phase in mammalian cells. (PMID:12859955)
• data suggest that HER-2 amplifications are frequently linked to alterations of the TOP2A gene in bladder cancer (PMID:14566826)
• demonstrated that neither A or B isoform has any preference for a specific DNA conformation as substrate under the conditions used in these experiments (PMID:14596941)
• Amplification and deletion of topoisomerase IIalpha gene (TOP2A) is common in breast neoplasms and may account for both sensitivity and resistance to topoII-inhibitor-chemotherapy. (PMID:14632727)
• Topoisomerase IIalpha activity concentrates at heterochromatin during interphase and mitosis. (PMID:14978217)
• Topo-II alpha is a useful marker for diagnosing liposarcoma. (PMID:14989736)
• overexpression of topoisomerase (DNA) II alpha is associated with gastric cancer (PMID:14991576)
• Chromosomes were condensed and aligned at metaphase in topo IIalpha-knockdown cells. (PMID:14996935)
• alterations in the ATP binding domain of the enzyme are capable of altering the interactions of TOP2A with DNA (PMID:15037624)
• UVA-modified DNA is preferentially targeted and processed by topoisomerase IIalpha and IIbeta. (PMID:15044480)
• topo IIalpha destabilization depends on the newly identified domain, GRDD (glucose-regulated destruction domain), which was mapped to the N-terminal 70-170 amino acid sequence (PMID:15126503)
• 1,4-benzoquinone stimulated DNA cleavage by topoisomerase IIalpha in cultured human cells (PMID:15182198)
• review commentary on TOP2A as a proliferation marker, indicator of drug sensitivity, and prognostic factor in mantle cell lymphoma (PMID:15201855)
• Increased expression of DNA topoisomerase II alpha is associated with female breast cancer (PMID:15375522)
• topoIIalpha plays an essential catalytic role in chromosome segregation that cannot be complemented by topoIIbeta (PMID:15456904)
• Human topoisomerase II alpha appears to ligate the two scissile bonds of a DNA cleavage site in a nonconcerted fashion. (PMID:15491148)
• Cisplatin was shown to strongly inhibit the decatenation and relaxation activity of isolated human DNA topoisomerase IIalpha. (PMID:15602006)
• low-level amplification of TIIalpha gene locus may be sporadic mechanism of increased TIIalpha protein expression in pediatric non-brainstem glioma, which can coincide with low-level amplification of Her-2/neu (PMID:15809708)
• topo2a and HER-2 status might have therapeutic and prognostic implications. (PMID:15899781)
• We show that a R162K mutation in human topoisomerase II alpha renders this enzyme highly resistant towards vanadate while having little effect on bisdioxopiperazine sensitivity. (PMID:16053917)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	top2a	ENSDARG00000024488
mus_musculus	Top2a	ENSMUSG00000020914
rattus_norvegicus	Top2a	ENSRNOG00000053047

Paralogs (1): TOP2B (ENSG00000077097)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98790) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 14 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal liver morphology	1
small spleen	1
small thymus	1
microphthalmia	1
abnormal seminal vesicle morphology	1
abnormal skin morphology	1
abnormal kidney morphology	1
increased mean corpuscular volume	1
increased circulating alkaline phosphatase level	1
increased circulating aspartate transaminase level	1
preweaning lethality, complete penetrance	1
enlarged urinary bladder	1
embryonic lethality prior to organogenesis	1
prenatal lethality prior to heart atrial septation	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Cricetulus longicaudatus	Q64399	98.6%	Diamond
Cricetulus griseus	P41515	92.7%	Diamond
Sus scrofa	O46374	91.3%	Diamond
Caenorhabditis elegans	Q23670	89.5%	Diamond
Gallus gallus	O42131	88.7%	Diamond
Leishmania chagasi	O61078	84.6%	Diamond
Crithidia fasciculata	P27570	84.6%	Diamond
Trypanosoma brucei brucei	P12531	78.0%	Diamond
Trypanosoma cruzi	P30190	78.0%	Diamond
Candida albicans	P87078	72.6%	Diamond
Meyerozyma guilliermondii ATCC 6260	Q01879	72.6%	Diamond
Saccharomyces cerevisiae S288C	P06786	72.0%	Diamond
Nakaseomyces glabratus CBS 138	O93794	71.9%	Diamond
Drosophila melanogaster	P15348	68.6%	Diamond
Bombyx mori	O16140	64.3%	Diamond
Lathyrus oleraceus	O24308	57.5%	Diamond
Arabidopsis thaliana	P30182	57.4%	Diamond
Penicillium chrysogenum	Q9Y8G8	56.7%	Diamond
Schizosaccharomyces pombe 972h-	P08096	56.4%	Diamond
Plasmodium falciparum K1	P41001	48.9%	Diamond
Dictyostelium discoideum	Q55BP5	48.3%	Diamond
Invertebrate iridescent virus 3	Q196X4	41.2%	Diamond
Invertebrate iridescent virus 6	Q9QSK1	41.0%	Diamond
Acanthamoeba polyphaga mimivirus	Q5UQE6	40.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GJD3-AS1	ncRNA	123706509
GJD3	protein-coding	125111
IGFBP4	protein-coding	3487
TNS4	protein-coding	84951

Protein

Protein identifiers

DNA topoisomerase 2-alpha — P11388 (reviewed: P11388)

Alternative names: DNA topoisomerase II, alpha isozyme

All UniProt accessions (3): J3KTB7, J3QR57, P11388

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homodimer. Interacts with COPS5. Interacts with RECQL5; this stimulates DNA decatenation. Interacts with SETMAR; stimulates the topoisomerase activity. Interacts with DHX9; this interaction occurs in a E2 enzyme UBE2I- and RNA-dependent manner, negatively regulates DHX9-mediated double-stranded DNA and RNA duplex helicase activity and stimulates TOP2A-mediated supercoiled DNA relaxation activity. Interacts with HNRNPU (via C-terminus); this interaction protects the topoisomerase TOP2A from degradation and positively regulates the relaxation of supercoiled DNA in a RNA-dependent manner. Interacts with MCM3AP isoform GANP. Interacts with ERCC6. Interacts with PLSCR1. Interacts with GCNA; this interaction allows the resolution of topoisomerase II (TOP2A) DNA-protein cross-links. Interacts with POL1RA/RPA1 (via dock II) and UBTF in the context of Pol I complex; may assist Pol I transcription initiation by releasing supercoils occurring during DNA unwinding. Interacts with TPRN; TPRN interacts with a number of DNA damage response proteins, is recruited to sites of DNA damage and may play a role in DNA damage repair. Interacts with FBXO28; this interaction leads to TOP2A proteasomal degradation.

Subcellular location. Cytoplasm. Nucleus. Nucleoplasm. Nucleolus.

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.

Post-translational modifications. Phosphorylation has no effect on catalytic activity. However, phosphorylation at Ser-1106 by CSNK1D/CK1 promotes DNA cleavable complex formation. (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1; leading to stabilized SUMOylated TOP2A trapped in cleavage complexes, which halts the DNA damage response to TOP2A-induced double-strand DNA breaks. SUMOylated. Ubiquitinated in a FBXO28-dependent manner; leading to TOP2A proteasomal degradation.

Activity regulation. Specifically inhibited by the intercalating agent amsacrine.

Cofactor. Binds two Mg(2+) per subunit. The magnesium ions form salt bridges with both the protein and the DNA. Can also accept other divalent metal cations, such as Mn(2+) or Ca(2+).

Domain organisation. The N-terminus has several structural domains; the ATPase domain (about residues 1-265), the transducer domain (about 266-428) and the toprim domain (455-572). Comparing different structures shows ATP hydrolysis induces domain shifts in the N-terminus that are probably part of the mechanism of DNA cleavage and rejoining.

Miscellaneous. Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.

Similarity. Belongs to the type II topoisomerase family.

Isoforms (4)

UniProt ID	Names	Canonical?
P11388-1	1	yes
P11388-2	2
P11388-3	3
P11388-4	4

RefSeq proteins (1): NP_001058* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001154	TopoII_euk	Family
IPR001241	Topo_IIA	Family
IPR002205	Topo_IIA_dom_A	Domain
IPR003594	HATPase_dom	Domain
IPR006171	TOPRIM_dom	Domain
IPR012542	DTHCT	Domain
IPR013506	Topo_IIA_bsu_dom2	Domain
IPR013757	Topo_IIA_A_a_sf	Homologous_superfamily
IPR013758	Topo_IIA_A/C_ab	Homologous_superfamily
IPR013759	Topo_IIA_B_C	Homologous_superfamily
IPR013760	Topo_IIA-like_dom_sf	Homologous_superfamily
IPR014721	Ribsml_uS5_D2-typ_fold_subgr	Homologous_superfamily
IPR018522	TopoIIA_CS	Conserved_site
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR031660	TOPRIM_C	Domain
IPR034157	TOPRIM_TopoII	Domain
IPR036890	HATPase_C_sf	Homologous_superfamily
IPR050634	DNA_Topoisomerase_II	Family

Pfam: PF00204, PF00521, PF01751, PF02518, PF08070, PF16898

Enzyme classification (BRENDA)

• EC 5.6.2.2 — DNA topoisomerase (ATP-hydrolysing) (BRENDA: 99 organisms, 409 substrates, 1698 inhibitors, 38 Km, 31 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0771–1.5	22
DNA	0.21–0.94	6
DATP	0.5–0.63	2
SUPERCOILED DNA	—	1

UniProt features (252 total): helix 59, strand 48, cross-link 45, modified residue 35, turn 10, site 10, binding site 9, mutagenesis site 7, sequence conflict 6, compositionally biased region 5, sequence variant 5, region of interest 5, splice variant 3, domain 2, chain 1, active site 1, short sequence motif 1

Structure

Experimental structures (PDB)

15 structures by resolution:

PDB	Title	Method	Resolution (Å)
5NNE	Crystal Structure of the first bromodomain of human BRD4 in complex with a diacetylated …	X-RAY DIFFRACTION	1.15
9BQB	Human Topoisomerase 2 Alpha ATPase domain bound to topobexin and non-hydrolyzable ATP …	X-RAY DIFFRACTION	1.5
1ZXM	Human Topo IIa ATPase/AMP-PNP	X-RAY DIFFRACTION	1.87
9BQ6	Human Topoisomerase 2 Alpha ATPase domain bound to non-hydrolyzable ATP analog AMPPNP	X-RAY DIFFRACTION	1.9
9BQ9	Human Topoisomerase 2 Alpha ATPase domain bound to obex 5c and non-hydrolyzable ATP …	X-RAY DIFFRACTION	1.95
9BQ7	Human Topoisomerase 2 Alpha ATPase domain bound to BNS22 and non-hydrolyzable ATP analog …	X-RAY DIFFRACTION	2.05
1ZXN	Human DNA topoisomerase IIa ATPase/ADP	X-RAY DIFFRACTION	2.51
4R1F	Re-refined Human DNA topoisomerase IIa (ATPase and transducer domains) in complex with …	X-RAY DIFFRACTION	2.51
8W50	Crystal structure of DNA binding and cleavage core of human topoisomerase 2-alpha in a …	X-RAY DIFFRACTION	2.67
4FM9	Human topoisomerase II alpha bound to DNA	X-RAY DIFFRACTION	2.9
5GWK	Human topoisomerase IIalpha in complex with DNA and etoposide	X-RAY DIFFRACTION	3.15
6ZY5	Cryo-EM structure of the Human topoisomerase II alpha DNA-binding/cleavage domain in …	ELECTRON MICROSCOPY	3.6
6ZY6	Cryo-EM structure of the Human topoisomerase II alpha DNA-binding/cleavage domain in …	ELECTRON MICROSCOPY	4.1
6ZY7	Cryo-EM structure of the entire Human topoisomerase II alpha in State 1	ELECTRON MICROSCOPY	4.64
6ZY8	Cryo-EM structure of the entire Human topoisomerase II alpha in State 2	ELECTRON MICROSCOPY	7.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11388-F1	75.33	0.38

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Isomerase, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, FDA approved drug targets, Small molecule drugs, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; nucleoli

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (11)

Position	Role
805	o-(5’-phospho-dna)-tyrosine intermediate
489	interaction with dna
492	interaction with dna
661	interaction with dna
662	interaction with dna
723	interaction with dna
757	interaction with dna
763	interaction with dna
804	transition state stabilizer
856	important for dna bending; intercalates between base pairs of target dna
931	interaction with dna

Ligand- & substrate-binding residues (9)

Position	Role
91	ATP
120	ATP
148–150	ATP
161–168	ATP
376–378	ATP
461	Mg(2+)
541	Mg(2+)
543	Mg(2+)

Post-translational modifications (80)

Type	Positions
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	1259, 1276, 1283, 1286, 1363, 1367, 1373, 1385, 1422, 1442, 1454, 1459, 1484, 1492, 17, 156, 157, 261, 352, 386, 397, 416, 418, 425, 440, 466, 480, 529, 584, 599, 614, 622, 625, 632, 639, 655, 662, 676, 1075, 1114 … (+4)
N-acetylmethionine	1
Phosphoserine	4, 1106, 1213, 1247, 1295, 1297, 1299, 1302, 1332, 1337, 1351, 1354, 1374, 1377, 1387, 1391, 1392, 1393, 1449, 1469, 1471, 1474, 1476, 1495, 1504, 1525
Phosphothreonine	282, 1205, 1244, 1327, 1343, 1470
N6-acetyllysine	1422, 1442
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	1240

Mutagenesis-validated functional residues (7)

Position	Phenotype
342–344	reduced enzyme activity; abolishes stimulation of atpase activity upon dna binding.
342–344	strongly reduced enzyme activity; abolishes stimulation of atpase activity upon dna binding.
461	impairs bending of target dna. strongly reduced dna cleavage.
541	impairs bending of target dna. strongly reduced dna cleavage.
543	impairs bending of target dna. strongly reduced dna cleavage.
545	strongly reduced dna cleavage.
1469	abolishes binding to the antibody mpm2.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 10; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

10 pathways:

ID	Pathway	Evidence
R-HSA-1362277	Transcription of E2F targets under negative control by DREAM complex	curated
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-1538133	G0 and Early G1	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-453279	Mitotic G1 phase and G1/S transition	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins	—
R-HSA-2990846	SUMOylation	—
R-HSA-4615885	SUMOylation of DNA replication proteins	electronic

MSigDB gene sets: 596 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_CIRCADIAN_RHYTHM, GOBP_CHROMOSOME_ORGANIZATION, KALMA_E2F1_TARGETS, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GNF2_MSH2, HORIUCHI_WTAP_TARGETS_DN, MODULE_451, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, GNF2_CENPF

GO Biological Process (13): resolution of meiotic recombination intermediates (GO:0000712), sister chromatid segregation (GO:0000819), DNA topological change (GO:0006265), chromatin organization (GO:0006325), DNA damage response (GO:0006974), chromosome segregation (GO:0007059), female meiotic nuclear division (GO:0007143), apoptotic chromosome condensation (GO:0030263), regulation of circadian rhythm (GO:0042752), positive regulation of apoptotic process (GO:0043065), positive regulation of single stranded viral RNA replication via double stranded DNA intermediate (GO:0045870), rhythmic process (GO:0048511), DNA metabolic process (GO:0006259)

GO Molecular Function (17): magnesium ion binding (GO:0000287), DNA binding (GO:0003677), chromatin binding (GO:0003682), RNA binding (GO:0003723), DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity (GO:0003918), protein kinase C binding (GO:0005080), ATP binding (GO:0005524), ATP-dependent activity, acting on DNA (GO:0008094), DNA binding, bending (GO:0008301), protein homodimerization activity (GO:0042803), ubiquitin binding (GO:0043130), protein heterodimerization activity (GO:0046982), nucleotide binding (GO:0000166), DNA topoisomerase activity (GO:0003916), protein binding (GO:0005515), isomerase activity (GO:0016853), metal ion binding (GO:0046872)

GO Cellular Component (12): chromosome, centromeric region (GO:0000775), condensed chromosome (GO:0000793), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex (GO:0009330), protein-containing complex (GO:0032991), ribonucleoprotein complex (GO:1990904), nuclear chromosome (GO:0000228), chromosome (GO:0005694), centriole (GO:0005814)

Reactome top-level categories

8 top-level categories:

Category	Pathways
G0 and Early G1	1
SUMO E3 ligases SUMOylate target proteins	1
Mitotic G1 phase and G1/S transition	1
Post-translational protein modification	1
SUMOylation	1
Cell Cycle, Mitotic	1
Metabolism of proteins	1
Cell Cycle	1

GO top-level categories

58 GO namespaces:

Category	Terms
nuclear lumen	3
intracellular membraneless organelle	3
nucleic acid binding	2
binding	2
catalytic activity, acting on DNA	2
DNA binding	2
protein dimerization activity	2
chromosome	2
cellular anatomical structure	2
reciprocal meiotic recombination	1
meiosis I cell cycle process	1
chromosome organization	1
nuclear chromosome segregation	1
DNA metabolic process	1
DNA conformation change	1
cellular component organization	1
cellular response to stress	1
cell cycle process	1
female gamete generation	1
meiotic cell cycle	1
meiotic nuclear division	1
chromosome condensation	1
apoptotic nuclear changes	1
circadian rhythm	1
regulation of biological process	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
single stranded viral RNA replication via double stranded DNA intermediate	1
positive regulation of viral genome replication	1
regulation of single stranded viral RNA replication via double stranded DNA intermediate	1
positive regulation of RNA biosynthetic process	1
biological_process	1
nucleic acid metabolic process	1
metal ion binding	1
DNA topoisomerase activity	1
ATP-dependent activity, acting on DNA	1
protein kinase binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
ATP hydrolysis activity	1
ATP-dependent activity	1
identical protein binding	1
ubiquitin-like protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid conformation isomerase activity	1
catalytic activity	1
cation binding	1
chromosomal region	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
catalytic complex	1
cellular_component	1
protein-containing complex	1
nucleus	1
microtubule organizing center	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 25 of 42 annotations. The rest are phylogenetic / computational / electronic (IEA).

25 experimentally-supported GO terms:

GO term	NS	Evidence
DNA damage response	BP	direct assay
DNA topological change	BP	direct assay
apoptotic chromosome condensation	BP	direct assay
chromatin organization	BP	mutant phenotype
chromosome segregation	BP	mutant phenotype
positive regulation of apoptotic process	BP	direct assay
positive regulation of single stranded viral RNA replication via double stranded DNA intermediate	BP	mutant phenotype
DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex	CC	direct assay
cytoplasm	CC	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
protein-containing complex	CC	direct assay
ribonucleoprotein complex	CC	direct assay
ATP-dependent activity, acting on DNA	MF	direct assay
DNA binding	MF	direct assay
DNA binding, bending	MF	direct assay
DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	MF	direct assay
RNA binding	MF	high-throughput assay
chromatin binding	MF	direct assay
magnesium ion binding	MF	direct assay
protein heterodimerization activity	MF	physical interaction
protein homodimerization activity	MF	physical interaction
protein kinase C binding	MF	physical interaction
ubiquitin binding	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 5,129 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOP2A	TOP1	P11387	977
TOP2A	TOP3A	Q13472	923
TOP2A	TOP1MT	Q969P6	869
TOP2A	NCAPG	Q9BPX3	852
TOP2A	CENPF	P49454	813
TOP2A	NEIL3	Q8TAT5	803
TOP2A	NCAPH	Q15003	801
TOP2A	TDP2	O95551	762
TOP2A	MKI67	P46013	750
TOP2A	CCNB2	O95067	720
TOP2A	CDK1	P06493	707
TOP2A	UBE2C	O00762	706
TOP2A	TDP1	Q9NUW8	700
TOP2A	NUSAP1	Q9BXS6	689
TOP2A	AURKA	O14965	686

IntAct

Human interaction partners of TOP2A in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

21 partners by confidence:

Partner	Interaction type	MIscore	Records
PRKCD	physical association	0.680	10
PARP1	association	0.600	1
CTNNB1	association	0.570	4
BRCA1	physical association	0.520	3
ARID1A	association	0.500	2
DHX16	physical association	0.400	1
FBXL13	physical association	0.400	1
FOXM1	physical association	0.400	1
H2BC9	physical association	0.400	1
H3-4	physical association	0.400	1
MAGT1	physical association	0.400	1
PIN1	physical association	0.400	1
RANBP2	physical association	0.400	1
RESF1	physical association	0.400	1
SMARCA4	physical association	0.400	1
TCF4	association	0.350	2
AIRE	association	0.350	1
ASB3	association	0.350	1
DNAJC21	association	0.350	1
RPL6	association	0.350	1
SLC20A1	association	0.350	1

BioGRID (744 interactions; top human partners by supporting records in a sample of 600 records): PIAS4 (Biochemical Activity; 6 records), ATM (Affinity Capture-Western; 5 records), HDAC1 (Affinity Capture-Western; 5 records), PARP1 (Proximity Label-MS; 5 records), RNF168 (Affinity Capture-MS; 5 records), SMURF2 (Affinity Capture-Western; 5 records), TP53 (Synthetic Growth Defect; 5 records), BRD4 (Affinity Capture-MS; 4 records), CDC5L (Affinity Capture-MS; 4 records), FBXO28 (Affinity Capture-MS; 4 records), GINS1 (Affinity Capture-MS; 4 records), MDM4 (Affinity Capture-Western; 4 records), RNF4 (Affinity Capture-MS; 4 records), CDT1 (Reconstituted Complex; 3 records), CHD4 (Affinity Capture-MS; 3 records)

SIGNOR signaling

showing 24 of 30 signaling interactions:

A	Effect	B	Mechanism
PLK3	up-regulates	TOP2A	phosphorylation
PLK1	up-regulates	TOP2A	phosphorylation
CSNK2A1	up-regulates	TOP2A	phosphorylation
NFY	“up-regulates quantity by expression”	TOP2A	“transcriptional regulation”
TOP2A	up-regulates	Chromosome_segregation
TOP2A	down-regulates	Survival
PRKCB	“up-regulates activity”	TOP2A	phosphorylation
PRKCG	“up-regulates activity”	TOP2A	phosphorylation
CSNK2A1	unknown	TOP2A	phosphorylation
“2-(Decan-2-ylamino)ethyl 4-aminobenzoate”	“down-regulates activity”	TOP2A	“chemical inhibition”
4’-epidoxorubicin	“down-regulates activity”	TOP2A	“chemical inhibition”
“Daunorubicin hydrochloride”	“down-regulates activity”	TOP2A	“chemical inhibition”
“Doxorubicin hydrochloride”	“down-regulates activity”	TOP2A	“chemical inhibition”
etoposide	“down-regulates activity”	TOP2A	“chemical inhibition”
idarubicin	“down-regulates activity”	TOP2A	“chemical inhibition”
teniposide	“down-regulates activity”	TOP2A	“chemical inhibition”
valrubicin	“down-regulates activity”	TOP2A	“chemical inhibition”
doxorubicin	“down-regulates activity”	TOP2A	“chemical inhibition”
CSNK2A1	“down-regulates quantity by destabilization”	TOP2A	phosphorylation
GSK3B	“down-regulates quantity by destabilization”	TOP2A	phosphorylation
SCF-FBW7	“down-regulates quantity by destabilization”	TOP2A	polyubiquitination
CDK1	unknown	TOP2A	phosphorylation
YAP1	“up-regulates quantity by expression”	TOP2A	“transcriptional regulation”
YAP/TAZ	“up-regulates quantity by expression”	TOP2A	“transcriptional regulation”

Protein complexes (CORUM) (9)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

9 complexes by size:

Complex	Subunits	Members
★ CDC5L complex	30	SRRM1, SF3B1, SRSF1, CDC5L, DYNC1H1, GCN1, HSPA8, PPP1CA, SF3B2, SCAF8, SNRPA, SRSF2, BZW1, RBMX, SFPQ, SNRPA1, SNRPD3, TCF4, PLRG1, SNRPD2, TOP2A, ILF2, SF3B4, SNRPD1, SFI1, BCAS2, CWC15, PPM1D, PRKDC, PRPF19
★ DNA synthesome complex, breast cancer MCF7 cells	23	POLA2, POLD3, POLE4, PRIM1, RFC1, RPA1, PCNA, POLD4, POLE2, POLE3, RFC4, TOP1, POLA1, RFC2, RFC3, RFC5, RPA2, RPA3, TOP2A, POLD1, POLD2, POLE, PRIM2
★ DNA synthesome complex, leukemia cells	19	PCNA, POLD1, RFC5, TOP2A, POLD4, PRIM1, PRIM2, RFC2, RPA2, TOP1, POLD2, POLD3, RPA1, POLA1, POLA2, RFC1, RFC3, RFC4, RPA3
★ CTCF-PARP1-HIS-KPNA-LMNA-TOP complex	9	TOP2A, NPM1, CTCF, H2AC18, H2AZ1, KPNA1, KPNA3, LMNA, PARP1
★ Toposome	7	SRPK1, SSRP1, TOP2A, DDX21, DHX9, HNRNPC, PRPF8
★ DHX9-TOP2A complex	2	DHX9, TOP2A
★ SETMAR-TOP2A complex	2	SETMAR, TOP2A
★ TOP2A-TOP2B complex	2	TOP2A, TOP2B
★ TOP2A homodimer	1	TOP2A

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the beta-catenin:TCF transactivating complex	5	33.4×	9e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — STAD.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for TOP2A: 162 ClinVar records (0 pathogenic / likely pathogenic); 1 CIViC cancer variant; 1 PharmGKB clinical annotation; 6 GWAS associations.

ClinVar

162 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	104
Likely benign	18
Benign	9

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 1,635):

Position(s)	Effect	Δscore	Sites
17:40389648–40389649	acceptor_loss	1.0000	3
17:40389963–40389964	donor_loss	1.0000	3
17:40390165	acceptor_loss	1.0000
17:40391504–40391505	donor_loss	1.0000	4
17:40391642	acceptor_loss	1.0000	2
17:40391643–40391648	acceptor_gain	1.0000	5
17:40391651–40391653	acceptor_gain	1.0000	2
17:40392342–40392343	acceptor_loss	1.0000	3
17:40392356–40392358	acceptor_gain	1.0000	2
17:40392578	donor_gain	1.0000

AlphaMissense

4,747 missense substitutions predicted likely pathogenic (of 10,237 scored), across 994 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M539	9	0.985	1.000
M102	9	0.964	0.998
M198	9	0.949	0.997
M537	9	0.940	0.999
M1131	9	0.931	0.992
M669	9	0.891	0.992
D541	8	1.000	1.000
D543	8	1.000	1.000
D545	8	1.000	1.000
D94	8	0.999	1.000
H548	8	0.999	1.000
H759	8	0.999	1.000
D86	8	0.998	0.999
N91	8	0.998	1.000
F628	8	0.998	1.000
F653	8	0.998	1.000
H758	8	0.998	1.000
D710	8	0.997	1.000
D720	8	0.997	0.999
H42	8	0.996	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

8 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	1.23e-10
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	4.32e-08
Liver Hepatocellular Carcinoma (validation)	unfavorable	5.19e-07
Kidney Chromophobe (TCGA)	unfavorable	2.5e-06
Kidney Renal Clear Cell Carcinoma (validation)	unfavorable	3.57e-06
Lung Adenocarcinoma (TCGA)	unfavorable	3.3e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	5.06e-05
Rectum Adenocarcinoma (validation)	favorable	0.000555

Disease associations

OMIM: gene MIM:126430 | disease phenotypes:

GWAS associations

6 associations:

Study	Trait	p-value
GCST90000025_668	Appendicular lean mass	4e-10
GCST004067_112	Hip circumference adjusted for BMI	1e-9
GCST90002399_325	Neutrophil percentage of white cells	5e-9
GCST004066_48	Hip circumference	4e-8
GCST004066_19	Hip circumference	9e-8
GCST004067_21	Hip circumference adjusted for BMI	3e-7

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1806 (SINGLE PROTEIN), CHEMBL2094255 (PROTEIN FAMILY), CHEMBL4106174 (PROTEIN FAMILY)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the TOP2A protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

9 curated-mechanism drugs:

Drug	Modality	Max phase
DAUNORUBICIN	Small molecule	4
DOXORUBICIN HYDROCHLORIDE	Small molecule	4
ETOPOSIDE PHOSPHATE	Small molecule	4
IDARUBICIN HYDROCHLORIDE	Small molecule	4
MITOXANTRONE HYDROCHLORIDE	Small molecule	4
VALRUBICIN	Small molecule	4
ALDOXORUBICIN	Small molecule	3
AMRUBICIN	Small molecule	3
GANCOTAMAB	Antibody	2

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes TOP2A — the drug acts on the assembly or class, not necessarily on this subunit alone.

8 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
AMSACRINE	DNA topoisomerase II	2	4
DEXRAZOXANE	DNA topoisomerase II	2	4
TENIPOSIDE	DNA topoisomerase II	2	4
BECATECARIN	DNA topoisomerase II	2	3
PAZUFLOXACIN	DNA topoisomerase II	2	3
VOSAROXIN	DNA topoisomerase II	2	3
BERUBICIN HYDROCHLORIDE	DNA topoisomerase II	2	2
C-1311	DNA topoisomerase II	2	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,980,119 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

19 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL178	DAUNORUBICIN	4	205,873
CHEMBL53463	DOXORUBICIN	4	317,622
CHEMBL359744	DOXORUBICIN HYDROCHLORIDE	4	143,174
CHEMBL44657	ETOPOSIDE	4	228,302
CHEMBL1117	IDARUBICIN	4	137,636
CHEMBL58	MITOXANTRONE	4	168,731
CHEMBL43	AMSACRINE	4	83,286
CHEMBL8	CIPROFLOXACIN	4	98,734
CHEMBL1738	DEXRAZOXANE	4	34,543
CHEMBL417	EPIRUBICIN	4	137,096
CHEMBL452231	TENIPOSIDE	4	137,895
CHEMBL84	TOPOTECAN	4	143,303
CHEMBL140	CURCUMIN	3	95,185
CHEMBL3317856	GEPOTIDACIN	3	236
CHEMBL283120	AXL-1717	2	1,818
CHEMBL3039513	DECERNOTINIB	2	1,509
CHEMBL83520	LOSOXANTRONE	2	26,756
CHEMBL1232279	NEMORUBICIN	2	15,799
CHEMBL203666	PIROXANTRONE	2	2,621

Clinical evidence (CIViC)

Drug × variant × indication, from 1 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

1 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
TOP2A EXPRESSION	Doxorubicin	Breast Cancer	Sensitivity/Response	CIViC B	EID909

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

EXPRESSION.

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs181501757	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs181501757	TOP2A	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs181501757	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele A is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele G.	PMID:29593529

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — DNA topoisomerases

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
etoposide	Inhibition	7.3	pIC50
myricetin	Inhibition	6.41	pIC50
doxorubicin	Inhibition	6.0	pIC50
mitoxantrone	Inhibition	5.28	pIC50

Binding affinities (BindingDB)

672 measured of 939 human assays (1010 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
9-(3,4-Dimethoxy-phenyl)-8H-furo[3’,4’:6,7]naphtho[2,3-d][1,3]dioxol-6-one	IC50	0.21 nM
CHEBI:42053	IC50	1.5 nM
SMR000466355	IC50	2.6 nM
NB-506 Analogue	EC50	8 nM
NB-506 Analogue	EC50	17 nM
Ginsenoside Rd	EC50	17 nM
ginsenoside-Rb1	EC50	17 nM
5,11-dimethyl-2H-pyrido[4,3-b]carbazole	IC50	19 nM
NB-506 Analogue	EC50	20 nM
CHEMBL108283	IC50	20 nM
NB-506 Analogue	EC50	25 nM
NB-506 Analogue	EC50	26 nM
NB-506 Analogue	EC50	30 nM
NB-506 Analogue	EC50	32 nM
NB-506 Analogue	EC50	42 nM
CHEMBL326664	IC50	45 nM
Edotecarin	EC50	51 nM
CHEMBL322325	IC50	54 nM
CHEMBL325543	IC50	63 nM
1,4-Dihydroxyanthrachinon	IC50	65 nM
2-[1,11-dihydroxy-5,7-dioxo-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-6-ylamino]ethyl cyanide	EC50	70 nM
CHEMBL2296491	IC50	76 nM
NB-506 Analogue	EC50	80 nM
1,11-dihydroxy-5,7-dioxo-6-(2-pyridylcarboxamido)-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole	EC50	90 nM
CHEMBL440642	EC50	96 nM
CHEMBL428339	EC50	98 nM
NB-506 Analogue	EC50	100 nM
CHEMBL108404	IC50	116 nM
CHEMBL2296492	IC50	125 nM
NB-506 Analogue	EC50	130 nM
CHEMBL2296490	IC50	132 nM
NB-506 Analogue	EC50	140 nM
4-[1,11-dihydroxy-5,7-dioxo-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-6-ylamino]benzoic acid	EC50	160 nM
CHEMBL7877	EC50	160 nM
CHEMBL269139	EC50	160 nM
5,8-Dihydroxy-2-(1-hydroxy-4-methyl-pent-3-enyl)-[1,4]naphthoquinone	IC50	190 nM
CHEMBL325588	IC50	226 nM
NB-506 Analogue	EC50	230 nM
CHEMBL4469453	IC50	230 nM
NB-506 Analogue	EC50	240 nM
CHEMBL135778	IC50	240 nM
6-amino-1,11-dihydroxy-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	270 nM
1,11-dihydroxy-6-(4-methylphenylsulfonamido)-5,7-dioxo-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole	EC50	270 nM
1,11-dihydroxy-6-(3-hydroxybenzylamino)-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	300 nM
NB-506 Analogue	EC50	300 nM
CHEMBL268458	EC50	330 nM
CHEMBL27233	EC50	330 nM
1,11-dihydroxy-6-methylamino-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	350 nM

ChEMBL bioactivities

364 potent at pChembl≥5 of 740 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.68	IC50	0.21	nM	CHEMBL440125
8.82	IC50	1.5	nM	NEMORUBICIN
8.59	IC50	2.6	nM	IDARUBICIN
8.52	IC50	3	nM	EPIRUBICIN
8.31	IC50	4.9	nM	DOXORUBICIN
8.05	IC50	9	nM	CHEMBL47027
8.00	IC50	10	nM	DAUNORUBICIN
7.70	IC50	20	nM	CHEMBL108283
7.52	EC50	30	nM	CIPROFLOXACIN
7.35	IC50	45	nM	CHEMBL326664
7.27	IC50	54	nM	CHEMBL322325
7.27	Kd	54.1	nM	CHEMBL3752910
7.25	Kd	56.27	nM	CHEMBL5653589
7.25	ED50	56.25	nM	CHEMBL3752910
7.23	ED50	58.51	nM	CHEMBL5653589
7.22	IC50	60	nM	CHEMBL346068
7.20	IC50	63	nM	CHEMBL325543
7.19	Kd	64	nM	DECERNOTINIB
7.12	IC50	76	nM	CHEMBL2296491
7.02	EC50	96	nM	CHEMBL440642
7.01	EC50	98	nM	CHEMBL428339
6.94	IC50	116	nM	CHEMBL108404
6.90	IC50	125	nM	CHEMBL2296492
6.88	IC50	132	nM	CHEMBL2296490
6.82	IC50	150	nM	CHEMBL47885
6.80	EC50	160	nM	CHEMBL7877
6.80	EC50	160	nM	CHEMBL269139
6.70	IC50	200	nM	CHEMBL4463643
6.66	IC50	220	nM	CHEMBL47526
6.65	IC50	226	nM	CHEMBL325588
6.64	IC50	230	nM	CHEMBL4469453
6.62	IC50	240	nM	CHEMBL135778
6.48	EC50	330	nM	CHEMBL27233
6.48	EC50	330	nM	CHEMBL268458
6.46	IC50	350	nM	CHEMBL2260090
6.44	EC50	360	nM	CHEMBL7690
6.41	IC50	390	nM	MYRICETIN
6.40	IC50	400	nM	ACONITINE
6.38	IC50	420	nM	CHEMBL137098
6.36	IC50	440	nM	CHEMBL4470431
6.36	IC50	440	nM	CHEMBL337526
6.32	IC50	480	nM	TOPOTECAN
6.31	Kd	486	nM	AXL-1717
6.31	IC50	490	nM	CHEMBL335700
6.30	EC50	500	nM	CHEMBL132098
6.30	EC50	500	nM	CHEMBL121666
6.30	IC50	500	nM	CHEMBL173975
6.30	IC50	500	nM	CHEMBL367883
6.29	IC50	510	nM	CHEMBL101299
6.26	EC50	550	nM	CHEMBL30104

PubChem BioAssay actives

227 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-(3,4-dimethoxyphenyl)-6H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one	2037013: Inhibition of Topo IIalpha (unknown origin)	ic50	0.0002	uM
Idarubicin	2037013: Inhibition of Topo IIalpha (unknown origin)	ic50	0.0026	uM
Epirubicin	2037013: Inhibition of Topo IIalpha (unknown origin)	ic50	0.0030	uM
Doxorubicin	2037013: Inhibition of Topo IIalpha (unknown origin)	ic50	0.0049	uM
Daunorubicin	2037013: Inhibition of Topo IIalpha (unknown origin)	ic50	0.0100	uM
tert-butyl N-[3-(acridin-9-ylamino)-5-(methylcarbamoyloxymethyl)phenyl]carbamate	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	0.0200	uM
N-[3-(acridin-9-ylamino)-5-(hydroxymethyl)phenyl]methanesulfonamide	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	0.0450	uM
N-[3-(acridin-9-ylamino)-5-(hydroxymethyl)phenyl]-4-(dimethylamino)butanamide	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	0.0540	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149636: Binding affinity to human TOP2A incubated for 45 mins by Kinobead based pull down assay	kd	0.0541	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149636: Binding affinity to human TOP2A incubated for 45 mins by Kinobead based pull down assay	kd	0.0563	uM
18-[(3R)-3-aminopyrrolidin-1-yl]-19-fluoro-22-oxo-16-oxa-1-azahexacyclo[15.7.1.02,15.05,14.06,11.021,25]pentacosa-2(15),3,5(14),6,8,10,12,17(25),18,20,23-undecaene-23-carboxylic acid	437020: Induction of poison effect at DNA topoisomerase 2 by G-quadruplex interaction polymerase stop assay	ic50	0.0600	uM
[3-(acridin-9-ylamino)-5-(methanesulfonamido)phenyl]methyl acetate	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	0.0630	uM
[3-(acridin-9-ylamino)-5-aminophenyl]methyl N-methylcarbamate	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	0.1160	uM
N-[4-(1-benzofuran-2-yl)-8-hydroxyquinolin-7-yl]acetamide	1527439: Inhibition of human topoisomerase 2alpha mediated decatenation using kDNA as susbtrate preincubated for 20 mins followed by substrate and ATP addition and measured after 1 hr by ethidium bromide staining based gel electrophoresis method	ic50	0.2000	uM
3,4,5-trihydroxy-N-[3-[(3,4,5-trihydroxybenzoyl)amino]phenyl]benzamide	57230: Inhibitory concentration against relaxation activity of DNA topoisomerase II by detecting the conversion of supercoiled pBR322 DNA to its relaxed form	ic50	0.2200	uM
[3-(acridin-9-ylamino)phenyl]methanol	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	0.2260	uM
2-chloro-3-[(4-fluorophenyl)methoxy-thiophen-2-ylmethyl]quinoline	1600554: Inhibition of DNA topoisomerase 2 in human MCF7 cells incubated for 18 to 24 hrs by kinase assay	ic50	0.2300	uM
methyl N-[[14-[2-(diethylamino)ethyl]-4-hydroxy-8-thia-14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2(7),3,5,9,11,13(16)-heptaen-10-yl]methyl]carbamate	211289: In vitro evaluation for inhibitor of human topoisomerase II from HeLa cells.	ec50	0.3300	uM
[(1S,2R,3R,4R,5R,6S,7S,8R,9R,10R,13R,14R,16S,17S,18R)-8-acetyloxy-11-ethyl-5,7,14-trihydroxy-6,16,18-trimethoxy-13-(methoxymethyl)-11-azahexacyclo[7.7.2.12,5.01,10.03,8.013,17]nonadecan-4-yl] benzoate	2037013: Inhibition of Topo IIalpha (unknown origin)	ic50	0.4000	uM
14-[(3R)-3-aminopyrrolidin-1-yl]-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.04,9.017,21]henicosa-2,4,6,8,10,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.4200	uM
2-chloro-3-[(4-chlorophenyl)methoxy-thiophen-2-ylmethyl]quinoline	1600554: Inhibition of DNA topoisomerase 2 in human MCF7 cells incubated for 18 to 24 hrs by kinase assay	ic50	0.4400	uM
14-[(3S)-3-aminopyrrolidin-1-yl]-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.04,9.017,21]henicosa-2,4,6,8,10,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.4400	uM
14-[(3S)-3-aminopyrrolidin-1-yl]-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.05,10.017,21]henicosa-2(11),3,5,7,9,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.4900	uM
2-[4-[5-[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenyl]furan-2-yl]phenyl]-1,4,5,6-tetrahydropyrimidine;dihydrochloride	57049: Inhibitory activity for 50% on topoisomerase II isolated from Giardia lamblia	ic50	0.5000	uM
N-[[1-[2-(diethylamino)ethylamino]-7-hydroxy-9-oxothioxanthen-4-yl]methyl]methanesulfonamide	211289: In vitro evaluation for inhibitor of human topoisomerase II from HeLa cells.	ec50	0.5000	uM
10-[(3S)-3-aminopyrrolidin-1-yl]-11-fluoro-14-oxo-8-oxa-1-azatetracyclo[7.7.1.02,7.013,17]heptadeca-2,4,6,9(17),10,12,15-heptaene-15-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.5100	uM
14-(3-aminopyrrolidin-1-yl)-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.05,10.017,21]henicosa-2(11),3,5,7,9,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.5500	uM
N-[[14-[2-(diethylamino)ethyl]-4-hydroxy-8-thia-14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2(7),3,5,9,11,13(16)-heptaen-10-yl]methyl]methanesulfonamide	211289: In vitro evaluation for inhibitor of human topoisomerase II from HeLa cells.	ec50	0.5500	uM
N-[4-(5-fluoro-2-hydroxyphenyl)-8-hydroxyquinolin-7-yl]-3-morpholin-4-ylpropanamide	1527439: Inhibition of human topoisomerase 2alpha mediated decatenation using kDNA as susbtrate preincubated for 20 mins followed by substrate and ATP addition and measured after 1 hr by ethidium bromide staining based gel electrophoresis method	ic50	0.6000	uM
15-fluoro-18-oxo-14-piperazin-1-yl-12-oxa-1-azapentacyclo[11.7.1.02,11.04,9.017,21]henicosa-2,4,6,8,10,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.6400	uM
N-[2-[[4-(2-aminoethylcarbamoyl)phenyl]methoxy]-4-carbamoylphenyl]-3,4-dichloro-5-methyl-1H-pyrrole-2-carboxamide;dihydrochloride	1994665: Inhibition of human DNA topoisomerase 2 alpha assessed as relaxation of supercoiled plasmid pNO1 DNA incubated for 30 mins by fluorescence based analysis	ic50	0.6700	uM
N-[8-hydroxy-4-[4-(trifluoromethyl)phenyl]quinolin-7-yl]acetamide	1527439: Inhibition of human topoisomerase 2alpha mediated decatenation using kDNA as susbtrate preincubated for 20 mins followed by substrate and ATP addition and measured after 1 hr by ethidium bromide staining based gel electrophoresis method	ic50	0.7000	uM
18-[(3S)-3-aminopyrrolidin-1-yl]-19-fluoro-22-oxo-16-oxa-1-azahexacyclo[15.7.1.02,15.05,14.06,11.021,25]pentacosa-2(15),3,5(14),6,8,10,12,17(25),18,20,23-undecaene-23-carboxylic acid	437020: Induction of poison effect at DNA topoisomerase 2 by G-quadruplex interaction polymerase stop assay	ic50	0.7000	uM
N-[4-(acridin-9-ylamino)-3-methoxyphenyl]methanesulfonamide	211292: Tested for inhibition of topoisomerase II isolated from HeLa cells by DNA-cleavage assay	ec50	0.7200	uM
14-[(3S)-3-aminopyrrolidin-1-yl]-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.03,8.017,21]henicosa-2(11),3,5,7,9,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.7200	uM
6-N-tert-butyl-8-ethyl-2-N-[2-(2-morpholin-4-ylethoxy)quinolin-6-yl]-7H-purine-2,6-diamine	1994665: Inhibition of human DNA topoisomerase 2 alpha assessed as relaxation of supercoiled plasmid pNO1 DNA incubated for 30 mins by fluorescence based analysis	ic50	0.7300	uM
12-butan-2-yl-11-imino-9-(4-methoxyphenyl)-2-oxa-4,6,12,14-tetrazatricyclo[8.4.0.03,8]tetradeca-1(10),3(8),13-triene-5,7-dione	1939819: Inhibition of DNA topoisomerase 2 (unknown origin)	ic50	0.7520	uM
14-(3-aminopyrrolidin-1-yl)-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.03,8.017,21]henicosa-2(11),3,5,7,9,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.7700	uM
14-(3-aminopyrrolidin-1-yl)-15-fluoro-18-oxo-12-oxa-1-azapentacyclo[11.7.1.02,11.04,9.017,21]henicosa-2,4,6,8,10,13(21),14,16,19-nonaene-19-carboxylic acid	211295: Inhibition of topoisomerase II as conversion of catenated to decatenated KDNA	ic50	0.7700	uM
12-(2-hydroxyphenyl)-11-imino-9-(4-methoxyphenyl)-2-oxa-4,6,12,14-tetrazatricyclo[8.4.0.03,8]tetradeca-1(10),3(8),13-triene-5,7-dione	1939819: Inhibition of DNA topoisomerase 2 (unknown origin)	ic50	0.7760	uM
7-imino-9-(4-methoxyphenyl)-11,13-dioxo-N-phenyl-2-oxa-4,6,12,14-tetrazatricyclo[8.4.0.03,8]tetradeca-1(10),3(8),4-triene-6-carbothioamide	1939819: Inhibition of DNA topoisomerase 2 (unknown origin)	ic50	0.7910	uM
Etoposide	211292: Tested for inhibition of topoisomerase II isolated from HeLa cells by DNA-cleavage assay	ec50	0.8100	uM
2-(2,4,5,8,9,11-hexazatetracyclo[10.4.0.02,6.07,11]hexadeca-1(16),3,5,7,9,12,14-heptaen-3-ylsulfanyl)-N-(3-methoxyphenyl)acetamide	1404822: Inhibition of human topoisomerase 2 using supercoiled pHOT1 DNA as substrate after 30 mins by agarose gel electrophoresis	ic50	0.8500	uM
6-amino-7-(1H-benzimidazol-2-yl)-5-[4-(dimethylamino)butyl]pyrrolo[2,3-b]pyrazine-2,3-dicarbonitrile	1274499: Inhibition of purified human topoisomerase 2-mediated relaxation of supercoiled pBR322 DNA at 50 uM incubated for 30 mins in presence of 1 mM ATP by agarose gel electrophoresis	ic50	0.9000	uM
N-(4-fluorophenyl)-2-(2,4,5,8,9,11-hexazatetracyclo[10.4.0.02,6.07,11]hexadeca-1(16),3,5,7,9,12,14-heptaen-3-ylsulfanyl)acetamide	1404822: Inhibition of human topoisomerase 2 using supercoiled pHOT1 DNA as substrate after 30 mins by agarose gel electrophoresis	ic50	0.9400	uM
Doxorubicin Hydrochloride	1663790: Inhibition of human DNA topoisomerase 2 catalytic activity using supercoiled pRYG DNA as substrate measured after 45 mins in presence of ATP by agarose gel electrophoresis	ic50	0.9400	uM
5-amino-10-[(3S)-3-aminopyrrolidin-1-yl]-11-fluoro-14-oxo-8-oxa-1-azatetracyclo[7.7.1.02,7.013,17]heptadeca-2(7),3,5,9(17),10,12,15-heptaene-15-carboxylic acid	1459334: Inhibition of human topoisomerase-2alpha assessed as reduction in enzyme-mediated decatenation using kinetoplast DNA as substrate after 15 mins by ethidium bromide staining based agarose gel electrophoresis method	ic50	0.9700	uM
N-[4-(pyridin-2-ylsulfamoyl)phenyl]-2-([1,2,4]triazolo[4,3-a]quinoxalin-4-ylsulfanyl)acetamide	1942562: Inhibition of human Topoisomerase 2 incubated for 30 mins by ELISA assay	ic50	0.9700	uM
2,4,6-trimethyl-N-(4-oxo-2-phenylchromen-7-yl)benzenesulfonamide	1663790: Inhibition of human DNA topoisomerase 2 catalytic activity using supercoiled pRYG DNA as substrate measured after 45 mins in presence of ATP by agarose gel electrophoresis	ic50	0.9800	uM
[3-(acridin-9-ylamino)-5-(4-oxopentanoylamino)phenyl]methyl 4-oxopentanoate	57198: In vitro 50% inhibition of topoisomerase II mediated k-DNA decatenation	ic50	1.0000	uM

CTD chemical–gene interactions

249 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Etoposide	affects cotreatment, affects binding, increases reaction, decreases reaction, decreases expression (+8 more)	18
Doxorubicin	affects response to substance, affects cotreatment, affects activity, decreases expression, increases expression (+6 more)	16
quinone	increases activity, increases expression, increases reaction, affects activity, affects binding (+1 more)	11
sodium arsenite	affects expression, decreases expression, increases expression	7
Amsacrine	increases stability, affects response to substance, decreases expression, decreases response to substance, increases phosphorylation (+1 more)	7
hydroquinone	affects activity, decreases activity, affects cotreatment, increases reaction	5
Fluorouracil	decreases expression, affects cotreatment, affects response to substance, affects reaction	5
bisphenol A	affects expression, decreases expression, increases expression	4
palbociclib	decreases expression, decreases reaction, increases expression, affects reaction	4
Adenosine Triphosphate	increases hydrolysis, decreases reaction	4
Cisplatin	affects cotreatment, decreases response to substance, affects expression, decreases expression, increases expression (+1 more)	4
Estradiol	increases expression, increases response to substance	4
Tretinoin	decreases expression, increases expression	4
Resveratrol	decreases activity, decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression	3
Curcumin	decreases expression, affects cotreatment	3
Progesterone	increases expression, decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Cyclosporine	decreases expression	3
Aflatoxin B1	decreases methylation, affects expression, affects cotreatment, increases expression	3
alternariol	decreases activity	2
triphenyl phosphate	affects expression, affects cotreatment, decreases expression	2
arsenite	affects binding, decreases reaction, increases expression	2
tris(1,3-dichloro-2-propyl)phosphate	decreases expression, affects cotreatment	2
cobaltous chloride	decreases expression	2
alternariol monomethyl ether	decreases activity	2
xanthatin	decreases activity, decreases expression, increases expression	2
perfluorooctanoic acid	decreases expression	2
1,2-naphthoquinone	affects activity, affects binding, decreases activity	2
copper-thiosemicarbazone complex	affects activity, decreases reaction, increases hydrolysis, decreases activity	2

ChEMBL screening assays

1305 unique, capped per target: 1264 binding, 22 admet, 13 functional, 6 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003545	Binding	Inhibition of human topoisomerase 2alpha-mediated supercoiled pBR322 DNA relaxation at 5 ug/ml by agarose gel electrophoresis	Makaluvamine N: a new pyrroloiminoquinone from Zyzzya fuliginosa. — *J Nat Prod*
CHEMBL3271407	ADMET	Inhibition of human topoisomerase-2-alpha mediated double-stranded catenated kinetoplast DNA decatenation after 30 mins by agarose gel electrophoresis in presence of ATP	Haloemodin as novel antibacterial agent inhibiting DNA gyrase and bacterial topoisomerase I. — *J Med Chem*
CHEMBL5355516	Toxicity	Poison activity at human topoisomerase 2alpha using pBR322 DNA as substrate assessed as stabilization of enzyme-DNA cleavage complex by measuring linear DNA formation upto 200 uM incubated for 30 mins by EtBr staining based UV light analysi	Synthesis and evaluation of 7-(3-aminopropyloxy)-substituted flavone analogue as a topoisomerase IIα catalytic inhibitor and its sensitizing effect to enzalutamide in castration-resistant prostate cancer cells. — *Eur J Med Chem*

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0B24	NYH/187/162	Cancer cell line	Male
CVCL_0B25	NYH/187/165	Cancer cell line	Male
CVCL_IP18	HL-60/AMSA	Cancer cell line	Female
CVCL_IP19	KBM-3/AMSA	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 68 trials:

NCT	Phase	Status	Title
NCT02513940	Phase 4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	Phase 4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	Phase 4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	Phase 4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	Phase 2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	Phase 2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	Phase 2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	Phase 1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	Phase 1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	Phase 1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	Phase 1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	Phase 1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	Phase 1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	Phase 1/2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT02931695	Not specified	COMPLETED	Ventricular Repolarization During the Pregnancy-to-Postpartum Transition (QuTe)
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea
NCT03775954	Not specified	RECRUITING	Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise
NCT03783975	Not specified	TERMINATED	KCNQ1 Cascade Screening
NCT03868657	Not specified	COMPLETED	The Physiological Effects of Human Ether-a-go-go-Related Gene (hERG)Blockade on Metabolism
NCT04074122	Not specified	UNKNOWN	Electromechanical Profiling of the Long-QT Syndrome (LQTS)
NCT04124237	Not specified	COMPLETED	Long Term Monitoring for Risk of Sudden Death
NCT04189822	Not specified	ENROLLING_BY_INVITATION	Hearts in Rhythm Organization (HiRO)National Registry and Bio Bank
NCT04328376	Not specified	COMPLETED	Measurement of the Electromechanical Window to Improve the Diagnosis of Congenital Long QT Syndrome
NCT04336644	Not specified	RECRUITING	Continuous Versus Intermittent cARdiac Electrical moNitorinG
NCT04441892	Not specified	TERMINATED	Low Cost QTc Meter for Long QT Syndrome Screening in Primary Care
NCT04650009	Not specified	COMPLETED	Physical Activity in Children With Inherited Cardiac Diseases
NCT04699097	Not specified	COMPLETED	The Effect of Azithromycin Use on Conduction System of Heart in COVID-19 Positive Children
NCT04706104	Not specified	COMPLETED	QT Measurement Techniques and Anesthesia Management
NCT04712136	Not specified	COMPLETED	Healthy-related Quality of Life and Physical Activity of Children With Cardiac Malformations
NCT04715256	Not specified	UNKNOWN	Evaluation of the Effects of KCNQ1 Mutation on Insulin Tolerance and Obsessive Compulsive Features in Long QT Romano-Ward Syndrome Patients.
NCT04728100	Not specified	COMPLETED	LQT and Smartphone/Smartwatch
NCT05274646	Not specified	COMPLETED	Impact on Risk Stratification of Overlap Syndrome Phenotype in Patients With E1784K Mutation in SCN5A
NCT05348564	Not specified	RECRUITING	Comparing Direct vs Indirect Methods for Cascade Screening
NCT05521451	Not specified	RECRUITING	Clinical Cohort Study - TRUST
NCT05903313	Not specified	UNKNOWN	A Study to Evaluate Accuracy and Validity of the Chang Gung ECG Abnormality Detection Software

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TOP2A across ~30M SureChEMBL compounds — explore on Sugi Predict.