TOP1

Summary

TOP1 (DNA topoisomerase I, HGNC:11986) is a protein-coding gene on chromosome 20q12, encoding DNA topoisomerase 1 (P11387). Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. In precision oncology, TOP1 Amplification confers sensitivity to Cetuximab + FOLFIRI Regimen in Colorectal Cancer (CIViC Level B); 3 further curated variant–drug associations are listed below. It is a common-essential gene (DepMap: required in 93.0% of cancer cell lines).

This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus altering the topology of DNA. This gene is localized to chromosome 20 and has pseudogenes which reside on chromosomes 1 and 22.

Source: NCBI Gene 7150 — RefSeq curated summary.

At a glance

• GWAS associations: 25 (top 5% of genes corpus-wide)
• Clinical variants (ClinVar): 31 total
• Regional missense constraint (gnomAD): 7 of 14 regions constrained (≈48% of expected missense variation)
• GTEx eGene: eQTL in 5 tissues, sQTL in 1 (q < 0.05)
• Drug target: yes — 24 curated mechanism-of-action drugs; 12 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 4 — Irinotecan Hydrochloride, Sacituzumab Govitecan, Topotecan Hydrochloride, +1 more
• Precision-oncology evidence (CIViC): 4 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 93.0% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.12 (highly constrained)
• MANE Select transcript: NM_003286
• Interaction hub: 3,224 STRING partners (top 2% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11986
Approved symbol	TOP1
Name	DNA topoisomerase I
Location	20q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198900
Ensembl biotype	protein_coding
OMIM	126420
Entrez	7150

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

MANE Select: ENST00000361337

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000361337, ENST00000680945, ENST00000681058, ENST00000681113, ENST00000681392, ENST00000681884, ENST00001026932, ENST00001078659, ENST00001107672, ENST00001111737, ENST00001132666

RefSeq mRNA: 1 — MANE Select: NM_003286 NM_003286

CCDS: CCDS13312

Canonical transcript exons

ENST00000361337 — 21 exons

Exon	Start	End
ENSE00000844695	41077582	41077637
ENSE00000844696	41080085	41080180
ENSE00000844697	41081165	41081240
ENSE00000844698	41084462	41084568
ENSE00000844699	41092472	41092587
ENSE00000844700	41097220	41097341
ENSE00000844701	41098215	41098337
ENSE00000844702	41100056	41100243
ENSE00000844703	41101209	41101353
ENSE00000844704	41112782	41112925
ENSE00000844706	41113970	41114155
ENSE00000844709	41115371	41115439
ENSE00000844711	41116278	41116392
ENSE00000844712	41118169	41118296
ENSE00000844716	41121696	41121790
ENSE00000844717	41122006	41122155
ENSE00001037776	41076171	41076294
ENSE00001159738	41123195	41124487
ENSE00001159739	41061394	41061490
ENSE00001174139	41029431	41029455
ENSE00001174143	41028822	41029100

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 121.3635 / max 2619.5462, expressed in 1826 samples.

Highest expression (Bgee): oocyte, ventricular zone, secondary oocyte, ganglionic eminence, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TOP1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 5 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

6 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Not Sun Exposed Suprapubic	eqtl	9.4e-04	-0.21	20:40997237:A:G
Cells Cultured fibroblasts	eqtl	4.6e-03	-0.24	20:41372315:C:G
Esophagus Mucosa	eqtl	1.0e-02	-0.12	20:41040316:G:T
Skin Sun Exposed Lower leg	sqtl	1.6e-02	+0.53	20:41265028:A:C
Adrenal Gland	eqtl	2.5e-02	+0.38	20:40470742:C:T
Nerve Tibial	eqtl	4.7e-02	-0.09	20:40951179:T:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
184619	88.3409	1825
184620	23.7300	1811
184621	9.2925	1703

Top tissues by expression

showing 100 of 291 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.27	gold quality
ventricular zone	UBERON:0003053	97.06	gold quality
secondary oocyte	CL:0000655	96.77	gold quality
ganglionic eminence	UBERON:0004023	96.77	gold quality
cortical plate	UBERON:0005343	96.09	gold quality
cervix squamous epithelium	UBERON:0006922	95.53	gold quality
pericardium	UBERON:0002407	95.09	gold quality
pylorus	UBERON:0001166	94.39	gold quality
vena cava	UBERON:0004087	94.38	gold quality
pancreatic ductal cell	CL:0002079	94.34	gold quality
superior surface of tongue	UBERON:0007371	94.20	gold quality
monocyte	CL:0000576	94.13	gold quality
pharyngeal mucosa	UBERON:0000355	94.12	gold quality
lymph node	UBERON:0000029	94.11	gold quality
islet of Langerhans	UBERON:0000006	94.02	gold quality
mononuclear cell	CL:0000842	93.95	gold quality
rectum	UBERON:0001052	93.80	gold quality
leukocyte	CL:0000738	93.76	gold quality
cardia of stomach	UBERON:0001162	93.51	gold quality
mammary duct	UBERON:0001765	93.10	gold quality
embryo	UBERON:0000922	92.85	gold quality
upper lobe of left lung	UBERON:0008952	92.80	gold quality
colonic epithelium	UBERON:0000397	92.62	gold quality
epithelium of mammary gland	UBERON:0003244	92.62	gold quality
upper lobe of lung	UBERON:0008948	92.61	gold quality
gall bladder	UBERON:0002110	92.59	gold quality
right lung	UBERON:0002167	92.49	gold quality
stromal cell of endometrium	CL:0002255	92.35	gold quality
tongue	UBERON:0001723	92.27	gold quality
tonsil	UBERON:0002372	92.09	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.04	gold quality
body of tongue	UBERON:0011876	91.95	gold quality
esophagus mucosa	UBERON:0002469	91.82	gold quality
mucosa of transverse colon	UBERON:0004991	91.52	gold quality
left adrenal gland	UBERON:0001234	91.50	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.49	gold quality
right adrenal gland cortex	UBERON:0035827	91.47	gold quality
adrenal cortex	UBERON:0001235	91.44	gold quality
right adrenal gland	UBERON:0001233	91.34	gold quality
esophagus squamous epithelium	UBERON:0006920	91.34	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.23	gold quality
vermiform appendix	UBERON:0001154	91.18	gold quality
peritoneum	UBERON:0002358	91.18	gold quality
omental fat pad	UBERON:0010414	91.16	gold quality
left adrenal gland cortex	UBERON:0035825	91.12	gold quality
caecum	UBERON:0001153	91.10	gold quality
renal medulla	UBERON:0000362	91.06	gold quality
left lobe of thyroid gland	UBERON:0001120	90.94	gold quality
transverse colon	UBERON:0001157	90.82	gold quality
vagina	UBERON:0000996	90.68	gold quality
decidua	UBERON:0002450	90.61	gold quality
squamous epithelium	UBERON:0006914	90.61	gold quality
spleen	UBERON:0002106	90.54	gold quality
small intestine	UBERON:0002108	90.52	gold quality
thyroid gland	UBERON:0002046	90.50	gold quality
adrenal gland	UBERON:0002369	90.46	gold quality
esophagus	UBERON:0001043	90.42	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.40	gold quality
blood	UBERON:0000178	90.36	gold quality
colonic mucosa	UBERON:0000317	90.34	gold quality
right lobe of thyroid gland	UBERON:0001119	90.24	gold quality
body of stomach	UBERON:0001161	90.22	gold quality
colon	UBERON:0001155	90.15	gold quality
pancreas	UBERON:0001264	89.98	gold quality
smooth muscle tissue	UBERON:0001135	89.84	gold quality
pons	UBERON:0000988	89.79	gold quality
lower esophagus mucosa	UBERON:0035834	89.77	gold quality
ectocervix	UBERON:0012249	89.75	gold quality
intestine	UBERON:0000160	89.61	gold quality
skin of abdomen	UBERON:0001416	89.60	gold quality
adenohypophysis	UBERON:0002196	89.57	gold quality
stomach	UBERON:0000945	89.55	gold quality
skin of leg	UBERON:0001511	89.53	gold quality
sural nerve	UBERON:0015488	89.51	gold quality
minor salivary gland	UBERON:0001830	89.50	gold quality
fundus of stomach	UBERON:0001160	89.48	gold quality
sigmoid colon	UBERON:0001159	89.46	gold quality
left uterine tube	UBERON:0001303	89.35	gold quality
left ovary	UBERON:0002119	89.33	gold quality
postcentral gyrus	UBERON:0002581	89.33	gold quality
large intestine	UBERON:0000059	89.29	gold quality
lower lobe of lung	UBERON:0008949	89.24	gold quality
cerebellar hemisphere	UBERON:0002245	89.15	gold quality
trigeminal ganglion	UBERON:0001675	89.12	gold quality
cerebellar cortex	UBERON:0002129	89.11	gold quality
parietal lobe	UBERON:0001872	89.03	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.98	gold quality
right ovary	UBERON:0002118	88.92	gold quality
primary visual cortex	UBERON:0002436	88.86	gold quality
saliva-secreting gland	UBERON:0001044	88.85	gold quality
right lobe of liver	UBERON:0001114	88.80	gold quality
endometrium	UBERON:0001295	88.75	gold quality
mouth mucosa	UBERON:0003729	88.74	gold quality
body of pancreas	UBERON:0001150	88.72	gold quality
lower esophagus	UBERON:0013473	88.71	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.70	gold quality
adult mammalian kidney	UBERON:0000082	88.69	gold quality
ovary	UBERON:0000992	88.62	gold quality
corpus callosum	UBERON:0002336	88.61	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8530	yes	763.90
E-CURD-114	yes	6.81
E-HCAD-9	yes	6.54
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	70.7	high
Tonsil	tissue	56.8	high
Lymph node	tissue	56.0	high
Thymus	tissue	54.9
Placenta	tissue	47.2	high
Appendix	tissue	47.1	high
Caudate putamen	tissue	46.1
Liver	tissue	44.5	medium
Putamen	tissue	41.7
Duodenum	tissue	40.2	high
Small intestine	tissue	40.1	high
Urinary bladder	tissue	39.9	high
Spinal cord	tissue	39.1
Choroid plexus	tissue	38.9
Olfactory bulb	tissue	38.3
Septum	tissue	37.7
Thalamus	tissue	37.3
Prefrontal cortex	tissue	37.2
Cerebral cortex	tissue	37.2	high
Corpus callosum	tissue	36.9
Midbrain	tissue	36.7
Occipital cortex	tissue	36.7
Superior colliculi	tissue	36.6
Hippocampal formation	tissue	36.5
Frontal cortex	tissue	36.4
Kidney	tissue	36.4	medium
Spleen	tissue	36.3	medium
Hypothalamus	tissue	36.2
Substantia nigra	tissue	36.0
Ventral forebrain	tissue	36.0
Medulla oblongata	tissue	35.7
Adipose tissue	tissue	35.5	low
Basal ganglia	tissue	35.2	high
Thyroid gland	tissue	35.2	high
Rectum	tissue	35.0	high
Motor cortex	tissue	35.0
Gallbladder	tissue	34.9	high
Periaqueductal gray	tissue	34.8
Adrenal gland	tissue	34.7	high
Colon	tissue	34.6	high
Pons	tissue	34.5
Somatosensory cortex	tissue	34.5
Stomach 1	tissue	34.4	high
Entorhinal cortex	tissue	33.5
Cerebellum	tissue	33.4	high
Esophagus	tissue	32.8	high
Epididymis	tissue	32.4	high
Retrosplenial and cingulate cortex	tissue	31.9
Temporal cortex	tissue	31.9
Amygdala	tissue	31.7
Retrosplenial cortex	tissue	31.6
Prostate	tissue	29.9	medium
Vagina	tissue	29.3	high
Lung	tissue	29.0	medium
Insular cortex	tissue	28.9
Postcentral gyrus	tissue	27.5
Pancreas	tissue	27.0	medium
Breast	tissue	26.2	medium
Endometrium 1	tissue	26.2	medium
Cervix	tissue	25.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Dorsal spinal cord (39.1), White matter (36.9), Dorsal hippocampus (36.5), Ventral spinal cord (36.3), Subiculum (35.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, E2F1, E2F4, MYC

miRNA regulators (miRDB)

Targeting TOP1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 128 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.122, missense Z 5.36 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000361337 splits into 14 regions with different missense tolerance; 7 are missense-constrained (≈48% 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
20:41,029,068–41,084,539	185 / 226.3	0.82	no
20:41,084,540–41,092,538	11 / 36.8	0.30	yes (p 2.1e-05)
20:41,092,539–41,100,058	84 / 119.2	0.70	no
20:41,100,059–41,100,211	14 / 66.1	0.21	yes (p 1.4e-10)
20:41,100,212–41,101,244	22 / 30.4	0.72	no
20:41,101,245–41,112,814	7 / 57.3	0.12	yes (p 3.0e-11)
20:41,112,815–41,112,858	14 / 22.2	0.63	no
20:41,112,859–41,114,053	8 / 61.9	0.13	yes (p 7.2e-12)
20:41,114,054–41,114,094	18 / 16.4	1.10	no
20:41,114,095–41,116,364	18 / 88.6	0.20	yes (p 6.3e-14)
20:41,116,365–41,118,187	18 / 20.5	0.88	no
20:41,118,188–41,121,726	13 / 56.8	0.23	yes (p 6.3e-09)
20:41,121,727–41,122,047	36 / 42.3	0.85	no
20:41,122,048–41,123,294	26 / 81.8	0.32	yes (p 7.0e-10)
DepMap (CRISPR cell-line fitness): dependent in 93.0% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): NCI-H226 (-2.272), TUHR10TKB (-2.199), NCI-H2052 (-1.701), SK-RC-52 (-1.655), AM-38 (-1.468), KP-N-RT-BM-1 (-1.461), JHH-6 (-1.451), TALL-1 (-1.449), RCC10RGB (-1.443), DK-MG (-1.41), SNU-668 (-1.369), T84 (-1.356), U-118 MG (-1.337), HCC1187 (-1.32), SNU-1033 (-1.296).

Literature-anchored findings (GeneRIF, showing 40)

• CPT-11 may provide therapeutic efficacy for esophageal squamous cell cancer and the effects correlate with the level of DNA topoisomerase I protein. (PMID:11749700)
• active site of a type I DNA topoisomerase from the kinetoplastid protozoan Leishmania donovani, compared to human structure (PMID:11809893)
• Different effects on human topoisomerase I by minor groove and intercalated deoxyguanosine adducts derived from two polycyclic aromatic hydrocarbon diol epoxides at or near a normal cleavage site. (PMID:11832494)
• Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecan (PMID:11844605)
• The origin recognition complex (ORC) marks a replication origin in the promoter (PMID:12004060)
• ATP and Topoisomerase I activity found indispensable for cDNA synthesis in the HIV-1 replication process. Mutant enzyme lacking activity inhibited HIV-1 infectivity (PMID:12051740)
• role of N-terminal domain in nucleolar localization of human DNA topoisomerase I (PMID:12119295)
• TOP1 delocalizes from the nucleolus to the nucleoplasm when sumoylated by camptothecin (PMID:12149243)
• binds to DNA first in an inactive conformation and then rearranges its active site for catalysis (PMID:12209008)
• DNA binding induces conformational transition within this enzyme in solution (PMID:12209444)
• presence of dna topoisomerase I in different testicular tumor types (PMID:12237772)
• Binding and dissociation of human emzyme with hairpin-loop RNAs: implications for the regulation of HIV-1 replication (PMID:12270136)
• RNA splicing factor ASF/SF2 inhibits human topoisomerase I mediated DNA relaxation (PMID:12270705)
• The x-ray crystal structure of human topoisomerase I covalently joined to double-stranded DNA & bound to Topotecan shows that Topotecan mimics a DNA base pair & binds at the DNA cleavage site, intercalating between the upstream & downstream base pairs. (PMID:12426403)
• proteins indentified binding to the N-terminal domain of human topoisomerase I (PMID:12549820)
• DNA is unwound bidirectionally by a ternary complex of T antigen, nucleolin and this enzyme. (PMID:12634843)
• The exon 2 region was required for physical binding of p14(ARF) to Topo I & stimulatory activity. p14(ARF) (R71A) was more efficient than wild-type to activate Topo I. Nucleolar location is linked the biological function of the ARF-Topo I complex. (PMID:12673200)
• The contributions of strong and week nonspecific electrostatic, van der Waals’s, and hydrophobic interactions, and hydrogen bonding of the enzymes to the complex formation with the single- and double-stranded DNAs were determined. (PMID:12708316)
• DNA relaxation by this enzyme occurs in the closed clamp conformation of the protein. (PMID:12711735)
• Factors affecting the specific recognition of topologically stressed DNA were analyzed on the basis of the thermodynamic and kinetic data on the Topo-DNA interaction and the X-ray data on human Topo (PMID:12723479)
• Human topoisomerase I plays an important role in HIV-1 replication and infectivity, and differences in the species specificity of HIV-1 infection can at least in part be attributed to differences in topoisomerase I activities. (PMID:12829794)
• a single mutation in the linker domain confers protein flexibility and camptothecin resistance to human topoisomerase I (PMID:12904303)
• Topo I activity is now shown to be involved in DNA damage/repair pathway in vivo (PMID:13679149)
• Lys(532) functions as a general acid during cleavage to protonate the leaving 5’-oxygen (PMID:14594810)
• topo I truncated up to position 210 is not stabilized by camptothecin in covalent DNA-complexes inside a living cell, whereas in vitro it retains full DNA-relaxation activity, and is targeted by camptothecin in the usual manner (PMID:14654701)
• topoisomerase I-mediated DNA damage and cell death is induced by hydrogen peroxide (PMID:14688260)
• human topoisomerase I exclusively dissociated HIV-1 reverse transcriptase, which strongly binds to structural RNAs (PMID:14706652)
• DNA damage at telomeric repeats by topoisomerase I is a prominent feature of camptothecin-induced apoptosis (PMID:14729676)
• Data describe the specific functions of individual N-terminal regions of topoisomerase I by characterizing mutants lacking amino acid residues 1-202 or 191-206 or having tryptophane-205 substituted by glycine. (PMID:14741206)
• p53 disruption has a dramatic effect on how glioblastoma cells process topoisomerase I inhibitor-mediated DNA damage. (PMID:14961077)
• topoisomerase I cleavage complexes correlate with apoptosis, however, at low UV doses the cleavage complex level was very low and the complexes were repaired (PMID:15010314)
• nucleolar/nucleoplasmic partitioning of topoisomerase I is regulated by interactions with RNA polymerase I and DNA but not by sumoylation (PMID:15014084)
• expression of human NUP98-TOP1 in murine bone marrow confers a potent in vitro growth advantage and a block in differentiation in hematopoietic precursors (PMID:15100157)
• Data report the synthesis of a number of oligonucleotides containing methylphosphonates at single positions for the purpose of investigating the hydrogen-bonding contacts necessary for human topoisomerase I function. (PMID:15147201)
• propose that arsenic trioxide induces topoisomerase I-DNA complexes that participate in chromatin fragmentation and programmed cell death during apoptosis (PMID:15178684)
• function for the automodification reaction is to regulate the interaction between PARP-1 and Topo I, and consequently, the Topo I activity, in response to DNA damage. (PMID:15247263)
• An essential component of this Top1/DNA active site model is the rotated +1 deoxyguanosine, and in vitro experiments and molecular modeling studies supported rotation of the +1 deoxyguanosine out of the helix (PMID:15351405)
• This is the first report that conjugated PUFA such as cEPA act as inhibitors of pols and topos. (PMID:15680922)
• The complexities of the relaxation reaction, the cellular roles, and the pathways that must exist to repair topoisomerase I-mediated DNA damage highlight the importance of continued study of this essential enzyme. (review) (PMID:15830206)
• Identification of 36 nuclear proteins that were associated with topoisomerase I. (PMID:15848144)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	top1a	ENSDARG00000070545
danio_rerio	top1b	ENSDARG00000086775
mus_musculus	Top1	ENSMUSG00000070544
rattus_norvegicus	Top1	ENSRNOG00000047611

Paralogs (1): TOP1MT (ENSG00000184428)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98788) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
embryonic lethality before implantation, complete penetrance	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
Pan troglodytes	A9Q1D5	98.8%	Diamond
Cricetulus griseus	Q07050	98.4%	Diamond
Chlorocebus aethiops	Q7YR26	97.7%	Diamond
Xenopus laevis	P41512	86.1%	Diamond
Candidozyma auris	A0A0L0P4F8	71.1%	Diamond
Candida albicans	Q00313	71.1%	Diamond
Daucus carota	P93119	69.7%	Diamond
Arabidopsis thaliana	Q9FJ79	69.7%	Diamond
Saccharomyces cerevisiae S288C	P04786	68.2%	Diamond
Drosophila melanogaster	P30189	67.3%	Diamond
Caenorhabditis elegans	O17966	64.0%	Diamond
Schizosaccharomyces pombe 972h-	P07799	56.9%	Diamond
Dictyostelium discoideum	Q54RC3	47.0%	Diamond
Mycosarcoma maydis	P41511	40.0%	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
SNHG35	ncRNA	101927098
PLCG1-AS1	ncRNA	101927117
SNORD154	snoRNA	109623474
MIR6871	ncRNA	102466912
ZHX3	protein-coding	23051
PLCG1	protein-coding	5335

Protein

Protein identifiers

DNA topoisomerase 1 — P11387 (reviewed: P11387)

Alternative names: DNA topoisomerase I

All UniProt accessions (3): A0A7P0T852, A0A7P0T9R7, P11387

UniProt curated annotations — full annotation on UniProt →

Function. Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3’-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5’-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5’-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the BMAL1 promoter.

Subunit / interactions. Monomer. Interacts with ERCC6. 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. (Microbial infection) Interacts with SV40 Large T antigen; this interactions allows viral DNA replication.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm.

Tissue specificity. Endothelial cells.

Post-translational modifications. Sumoylated. Lys-117 is the main site of sumoylation. Sumoylation plays a role in partitioning TOP1 between nucleoli and nucleoplasm. Levels are dramatically increased on camptothecin (CPT) treatment. Phosphorylation at Ser-506 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin.

Disease relevance. A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.

Activity regulation. Specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity.

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 IB topoisomerase family.

RefSeq proteins (1): NP_003277* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001631	TopoI	Family
IPR008336	TopoI_DNA-bd_euk	Domain
IPR011010	DNA_brk_join_enz	Homologous_superfamily
IPR013030	DNA_topo_DNA_db_N_dom2	Homologous_superfamily
IPR013034	DNA_topo_DNA_db_N_dom1	Homologous_superfamily
IPR013499	TopoI_euk	Domain
IPR013500	TopoI_cat_euk	Domain
IPR014711	TopoI_cat_a-hlx-sub_euk	Homologous_superfamily
IPR014727	TopoI_cat_a/b-sub_euk	Homologous_superfamily
IPR018521	TopoIB_AS	Active_site
IPR025834	TopoI_C_dom	Domain
IPR036202	TopoI_DNA-bd_euk_N_sf	Homologous_superfamily
IPR048045	Topoisomer_I_DNA-bd	Domain
IPR051062	Topoisomerase_IB	Family

Pfam: PF01028, PF02919, PF14370

Enzyme classification (BRENDA)

• EC 5.6.2.1 — DNA topoisomerase (BRENDA: 73 organisms, 262 substrates, 1102 inhibitors, 6 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NEGATIVELY SUPERCOILED PLASMID PXXZ06 DNA	—	1

UniProt features (123 total): helix 33, strand 20, cross-link 19, site 9, turn 8, modified residue 8, sequence variant 6, mutagenesis site 6, compositionally biased region 5, region of interest 4, initiator methionine 1, chain 1, active site 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

15 structures by resolution:

PDB	Title	Method	Resolution (Å)
1A31	HUMAN RECONSTITUTED DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX	X-RAY DIFFRACTION	2.1
1K4T	HUMAN DNA TOPOISOMERASE I (70 KDA) IN COMPLEX WITH THE POISON TOPOTECAN AND COVALENT …	X-RAY DIFFRACTION	2.1
1RRJ	Structural Mechanisms of Camptothecin Resistance by Mutations in Human Topoisomerase I	X-RAY DIFFRACTION	2.3
1A35	HUMAN TOPOISOMERASE I/DNA COMPLEX	X-RAY DIFFRACTION	2.5
1EJ9	CRYSTAL STRUCTURE OF HUMAN TOPOISOMERASE I DNA COMPLEX	X-RAY DIFFRACTION	2.6
1RR8	Structural Mechanisms of Camptothecin Resistance by Mutations in Human Topoisomerase I	X-RAY DIFFRACTION	2.6
1A36	TOPOISOMERASE I/DNA COMPLEX	X-RAY DIFFRACTION	2.8
1SC7	Human DNA Topoisomerase I (70 Kda) In Complex With The Indenoisoquinoline MJ-II-38 and …	X-RAY DIFFRACTION	3
1SEU	Human DNA Topoisomerase I (70 Kda) In Complex With The Indolocarbazole SA315F and …	X-RAY DIFFRACTION	3
1T8I	Human DNA Topoisomerase I (70 Kda) In Complex With The Poison Camptothecin and Covalent …	X-RAY DIFFRACTION	3
1NH3	Human Topoisomerase I Ara-C Complex	X-RAY DIFFRACTION	3.1
1TL8	Human DNA topoisomerase I (70 kDa) in complex with the indenoisoquinoline AI-III-52 and …	X-RAY DIFFRACTION	3.1
1R49	Human topoisomerase I (Topo70) double mutant K532R/Y723F	X-RAY DIFFRACTION	3.13
1LPQ	Human DNA Topoisomerase I (70 Kda) In Non-Covalent Complex With A 22 Base Pair DNA Duplex …	X-RAY DIFFRACTION	3.14
1K4S	HUMAN DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11387-F1	80.25	0.70

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Isomerase, Predicted intracellular proteins, Cancer-related genes, Disease related genes, FDA approved drug targets, Biotech drugs, Small molecule drugs, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli fibrillar center; nucleoplasm

Antibody reliability (HPA): IH supported · 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 (10)

Position	Role
723	o-(3’-phospho-dna)-tyrosine intermediate
316	interaction with dna
364	interaction with dna
412	interaction with dna
443	interaction with dna
501	interaction with dna
532	interaction with dna
574	interaction with dna
632	interaction with dna
650	interaction with dna

Post-translational modifications (27)

Type	Positions
N-acetylserine	2
Phosphoserine	2, 10, 57, 112, 506
N6-acetyllysine	172, 280
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	101, 103, 117, 134, 148, 153, 158, 164, 172, 204, 336, 549, 642, 700, 712
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo)	103, 117, 153
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	117

Mutagenesis-validated functional residues (6)

Position	Phenotype
103	localizes in both nucleoplasm and nucleoli; when associated with r-117 or r-153. almost complete loss of sumoylation, concentrates in …
117	5-fold decrease in sumoylation. localizes in both nucleoplasm and nucleoli; when associated with or without r-103 or r-153. almost complete …
153	localizes in both nucleoplasm and nucleoli; when associated with r-103 or r-117. almost complete loss of sumoylation, concentrates in …
532	almost abolishes enzyme activity.
532	strongly reduced enzyme activity.
723	no change in cpt-induced clearing from nuclei.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-4615885	SUMOylation of DNA replication proteins	curated
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins	—
R-HSA-2990846	SUMOylation	—

MSigDB gene sets: 414 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_CIRCADIAN_RHYTHM, GOBP_CHROMOSOME_ORGANIZATION, E2F_Q4_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_RESPONSE_TO_IONIZING_RADIATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, MORF_UBE2I, GEORGES_CELL_CYCLE_MIR192_TARGETS, GOBP_REGENERATION, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, FOXO4_01, KAUFFMANN_DNA_REPAIR_GENES

GO Biological Process (15): DNA replication (GO:0006260), DNA topological change (GO:0006265), chromatin remodeling (GO:0006338), chromosome segregation (GO:0007059), circadian rhythm (GO:0007623), response to temperature stimulus (GO:0009266), rRNA transcription (GO:0009303), response to xenobiotic stimulus (GO:0009410), response to gamma radiation (GO:0010332), programmed cell death (GO:0012501), animal organ regeneration (GO:0031100), circadian regulation of gene expression (GO:0032922), response to cAMP (GO:0051591), cellular response to luteinizing hormone stimulus (GO:0071373), rhythmic process (GO:0048511)

GO Molecular Function (18): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA binding (GO:0003677), chromatin binding (GO:0003682), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), DNA topoisomerase type I (single strand cut, ATP-independent) activity (GO:0003917), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), DNA binding, bending (GO:0008301), protein domain specific binding (GO:0019904), chromatin DNA binding (GO:0031490), protein-containing complex binding (GO:0044877), supercoiled DNA binding (GO:0097100), molecular condensate scaffold activity (GO:0140693), DNA topoisomerase activity (GO:0003916), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (11): P-body (GO:0000932), fibrillar center (GO:0001650), dense fibrillar component (GO:0001651), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), protein-DNA complex (GO:0032993), perikaryon (GO:0043204), nuclear chromosome (GO:0000228), cytoplasm (GO:0005737)

Reactome top-level categories

4 top-level categories:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1

GO top-level categories

52 GO namespaces:

Category	Terms
DNA binding	5
cellular anatomical structure	5
binding	3
nuclear lumen	3
DNA metabolic process	2
nucleic acid binding	2
nucleolus	2
intracellular membraneless organelle	2
DNA biosynthetic process	1
DNA conformation change	1
chromatin organization	1
cell cycle process	1
rhythmic process	1
response to abiotic stimulus	1
DNA-templated transcription	1
rRNA metabolic process	1
response to chemical	1
response to ionizing radiation	1
signal transduction	1
cell death	1
regeneration	1
animal organ development	1
circadian rhythm	1
regulation of gene expression	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
response to luteinizing hormone	1
cellular response to gonadotropin stimulus	1
cellular response to peptide hormone stimulus	1
biological_process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
DNA topoisomerase activity	1
protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein binding	1
chromatin binding	1
double-stranded DNA binding	1
protein-macromolecule adaptor activity	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on DNA	1
catalytic activity	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
protein-containing complex	1
neuronal cell body	1
nucleus	1
chromosome	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 24 of 44 annotations. The rest are phylogenetic / computational / electronic (IEA).

24 experimentally-supported GO terms:

GO term	NS	Evidence
DNA topological change	BP	direct assay
chromatin remodeling	BP	mutant phenotype
circadian regulation of gene expression	BP	mutant phenotype
circadian rhythm	BP	expression pattern
response to xenobiotic stimulus	BP	expression pattern
P-body	CC	direct assay
fibrillar center	CC	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
protein-DNA complex	CC	mutant phenotype
ATP binding	MF	mutant phenotype
DNA binding	MF	direct assay
DNA binding, bending	MF	experiment
DNA topoisomerase type I (single strand cut, ATP-independent) activity	MF	direct assay
RNA binding	MF	high-throughput assay
RNA polymerase II cis-regulatory region sequence-specific DNA binding	MF	direct assay
chromatin binding	MF	direct assay
double-stranded DNA binding	MF	mutant phenotype
molecular condensate scaffold activity	MF	direct assay
protein domain specific binding	MF	physical interaction
protein serine/threonine kinase activity	MF	mutant phenotype
single-stranded DNA binding	MF	mutant phenotype
supercoiled DNA binding	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 3,224 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOP1	TOP2A	P11388	977
TOP1	TDP1	Q9NUW8	972
TOP1	TOP3A	Q13472	945
TOP1	TOP3B	O95985	871
TOP1	TOP2B	Q02880	853
TOP1	DDX4	Q9NQI0	758
TOP1	PPP1CC	P36873	757
TOP1	DDX3Y	O15523	753
TOP1	BTBD1	Q9H0C5	752
TOP1	TDP2	O95551	741
TOP1	H2AX	P16104	739
TOP1	BTBD2	Q9BX70	719
TOP1	LIG3	P49916	718
TOP1	MUS81	Q96NY9	682
TOP1	CENPC	Q03188	661

IntAct

Human interaction partners of TOP1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

20 partners by confidence:

Partner	Interaction type	MIscore	Records
NKX3-1	physical association	0.630	6
ABL1	physical association	0.600	7
HNRNPR	association	0.600	3
NCL	direct interaction	0.590	1
WAS	association	0.560	3
ADAMTS16	physical association	0.400	1
ALDH1B1	physical association	0.400	1
ALDH2	physical association	0.400	1
ASXL3	physical association	0.400	1
H2BC21	physical association	0.400	1
SLC25A3	physical association	0.400	1
TOPBP1	physical association	0.400	1
TPR	physical association	0.400	1
CDK14	association	0.350	1
DDX39A	association	0.350	1
ESAM	association	0.350	1
PA	association	0.350	1
MYC	physical association	0.000	1
SMAD2	physical association	0.000	1
TIAM1	physical association	0.000	1

BioGRID (922 interactions; top human partners by supporting records in a sample of 600 records): BRCA1 (Negative Genetic; 7 records), PRKDC (Affinity Capture-MS; 6 records), XRCC6 (Affinity Capture-MS; 6 records), CDKN2A (Affinity Capture-Western; 5 records), PIAS4 (Affinity Capture-MS; 5 records), XRCC5 (Affinity Capture-MS; 5 records), BRD2 (Affinity Capture-MS; 4 records), NCL (Affinity Capture-Western; 4 records), TP53 (Affinity Capture-Western; 4 records), BRD4 (Affinity Capture-MS; 3 records), CDT1 (Affinity Capture-MS; 3 records), CHD4 (Affinity Capture-MS; 3 records), EAF1 (Affinity Capture-MS; 3 records), ERCC6 (Affinity Capture-MS; 3 records), PARP1 (Proximity Label-MS; 3 records)

SIGNOR signaling

showing 11 of 12 signaling interactions:

A	Effect	B	Mechanism
irinotecan	“down-regulates activity”	TOP1	“chemical inhibition”
topotecan	“down-regulates activity”	TOP1	“chemical inhibition”
ABL1	“up-regulates activity”	TOP1	phosphorylation
PRKDC	“down-regulates quantity by destabilization”	TOP1	phosphorylation
BRCA1	“down-regulates quantity by destabilization”	TOP1	ubiquitination
NONO	up-regulates	TOP1	binding
SFPQ	up-regulates	TOP1	binding
TOP1	“down-regulates quantity by repression”	ARNTL	“transcriptional regulation”
PRKCA	“up-regulates activity”	TOP1	phosphorylation
CSNK2A1	“up-regulates activity”	TOP1	phosphorylation
CDK1	“up-regulates activity”	TOP1	phosphorylation

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
★ Nop56p-associated pre-rRNA complex	104	LUC7L2, NCL, RPL27, RPL29, RPL39, RPL7, RPS23, RPS6, MYBBP1A, RPL21, RPL28, RPL5, RPS9, U2AF2, LYAR, RPL13, RPL23, RPL23A, RPL35A, RPL4, RPS24, HNRNPA1, EBNA1BP2, RPLP1, RPS17, U2AF1, DHX9, RPL30, SCYL2, RPL11, RPS11, NOLC1, RPL12, RPL14, RPL17, RPL19, RPL32, RPS13, RPS8, NOP58, RPL36A, RPLP2, RPS2, RPS29, SRP14, TCOF1, TUFM, ACTG2, RBM28, RPL10, RPL37A, RPS12, RPS7, TUBB1, BRIX1, DDX21, GNL3, IGF2BP1, ILF2, RPL10A, RPL15, RPLP0, EEF2, HNRNPU, NOP56, RPL26, RPL3, RPS14, RPS16, RSL1D1, ACTA2, EEF1A1, H1-3, RPL24, RPL6, RPL8, SRPK1, TOP1, FBL, HNRNPM, RPL13A, RPL31, RPL7A, RPS18, H1-10, ILF3, NPM1, RPS15A, TUBA1A, YBX1, H2BC14, PWP1, RPL18A, RPL22, RPL27A, RPS15, RPS3A, SLC25A5, NAP1L1, RPL18, RPL35, RPL36, RPL9, SNU13
★ RC complex, S-phase-specific	23	POLD4, POLE2, POLE4, CCNA2, CDK2, POLD2, POLD3, RFC2, POLE, RFC1, RFC5, RPA3, LIG1, PARP1, POLA1, POLD1, RFC3, RPA2, POLA2, POLE3, RFC4, RPA1, TOP1
★ 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
★ RC complex, G2/M-phase-specific	19	CCNB1, POLA1, POLA2, POLD2, RPA1, RPA2, CDK1, POLD3, RFC1, RFC2, RPA3, POLD1, POLD4, POLE, POLE3, PARP1, POLE2, POLE4, TOP1
★ 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
★ TFIIIC containing-TOP1-SUB1 complex	7	TOP1, GTF3C1, GTF3C2, GTF3C3, GTF3C4, GTF3C5, SUB1
★ TRBP-DNA-PK complex	7	PARP1, PRKDC, TOP1, XRCC5, XRCC6, NCOA6, NUMA1
★ NARC1 complex	5	ALYREF, CDC5L, PRPF19, RBMX, TOP1
★ TOP1-PSF-P54 complex	3	NONO, SFPQ, TOP1

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — BCC, HCC.

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 TOP1: 31 ClinVar records (0 pathogenic / likely pathogenic); 2 CIViC cancer variants; 1 PharmGKB clinical annotation; 25 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	4

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 1,321):

Position(s)	Effect	Δscore	Sites
20:41029101–41029102	donor_loss	1.0000	4
20:41061392–41061393	acceptor_loss	1.0000	6
20:41061491–41061492	donor_loss	1.0000	5
20:41076169	acceptor_loss	1.0000
20:41076290	donor_gain	1.0000
20:41076295–41076296	donor_loss	1.0000	5
20:41077580–41077581	acceptor_loss	1.0000	2
20:41077638–41077639	donor_loss	1.0000	5
20:41080083–41080084	acceptor_loss	1.0000	6
20:41080177	donor_gain	1.0000

AlphaMissense

2,480 missense substitutions predicted likely pathogenic (of 5,182 scored), across 519 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
M428	9	0.970	0.997
M470	9	0.965	0.996
M370	9	0.962	0.993
M263	9	0.876	0.991
M581	9	0.864	0.983
M758	9	0.859	0.962
H632	8	1.000	1.000
D440	8	0.999	1.000
D533	8	0.999	1.000
D725	8	0.999	0.999
D483	8	0.998	0.999
F529	8	0.998	1.000
F565	8	0.997	1.000
H367	8	0.996	1.000
F589	8	0.996	1.000
N631	8	0.995	1.000
F752	8	0.994	1.000
F554	8	0.993	0.999
F361	8	0.991	1.000
H222	8	0.990	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (validation)	unfavorable	1.85e-05
Lung Adenocarcinoma (validation)	unfavorable	0.000137
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000255

Disease associations

OMIM: gene MIM:126420 | disease phenotypes:

GWAS associations

25 associations:

Study	Trait	p-value
GCST90013407_19	Liver enzyme levels (gamma-glutamyl transferase)	2e-42
GCST004233_45	LDL cholesterol levels	2e-34
GCST004235_27	Total cholesterol levels	5e-29
GCST000759_34	LDL cholesterol	3e-19
GCST009365_23	LDL cholesterol levels x short total sleep time interaction (2df test)	8e-19
GCST002222_16	LDL cholesterol	5e-18
GCST000760_36	Cholesterol, total	3e-17
GCST002221_17	Cholesterol, total	1e-16
GCST006661_185	Male-pattern baldness	2e-15
GCST009366_53	LDL cholesterol levels x long total sleep time interaction (2df test)	2e-15
GCST90002384_73	Hemoglobin	2e-10
GCST008972_204	Urate levels	4e-10
GCST010002_342	Refractive error	7e-10
GCST010703_113	Brain morphology (MOSTest)	1e-9
GCST90020028_594	Hip circumference adjusted for BMI	3e-9
GCST90002403_44	Red blood cell count	4e-9
GCST010321_165	PR interval	2e-8
GCST90020027_877	Waist-hip index	3e-8
GCST90020025_1939	Waist-to-hip ratio adjusted for BMI	4e-8
GCST010320_132	PR interval	5e-8
GCST004235_1	Total cholesterol levels	1e-6
GCST004233_32	LDL cholesterol levels	3e-6
GCST004253_8	Accelerated cognitive decline after conversion of mild cognitive impairment to Alzheimer’s disease (Alzhiemer’s diagnosis trajectory interaction)	4e-6
GCST009302_14	Antipsychotic drug-induced weight gain in schizophrenia	4e-6
GCST009391_1697	Metabolite levels	8e-6

EFO canonical traits (from GWAS)

13 canonical traits:

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0007710	cognitive decline measurement
EFO:0004531	urate measurement
EFO:0004567	antipsychotic drug related weight gain
EFO:0010542	ureidopropionic acid measurement
EFO:0004462	PR interval
EFO:0004346	neuroimaging measurement
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1781 (SINGLE PROTEIN), CHEMBL4106174 (PROTEIN FAMILY)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the TOP1 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.

24 curated-mechanism drugs:

Drug	Modality	Max phase
IRINOTECAN HYDROCHLORIDE	Small molecule	4
SACITUZUMAB GOVITECAN	Antibody drug conjugate	4
TOPOTECAN HYDROCHLORIDE	Small molecule	4
TRASTUZUMAB DERUXTECAN	Antibody drug conjugate	4
BECATECARIN	Small molecule	3
BELOTECAN	Small molecule	3
DATOPOTAMAB DERUXTECAN	Antibody drug conjugate	3
EDOTECARIN	Small molecule	3
ETIRINOTECAN PEGOL	Unknown	3
EXATECAN	Small molecule	3
IRINOTECAN SUCROSOFATE	Unknown	3
KARENITECIN	Small molecule	3
PATRITUMAB DERUXTECAN	Antibody drug conjugate	3
RUBITECAN	Small molecule	3
7-ETHYL-10-HYDROXYCAMPTOTHECIN	Small molecule	2
9-AMINOCAMPTOTHECIN	Small molecule	2
AFELETECAN	Small molecule	2
AR-67	Small molecule	2
CAMPTOTHECIN-20-O-PROPIONATE	Small molecule	2
DIFLOMOTECAN	Small molecule	2
GIMATECAN	Small molecule	2
LABETUZUMAB GOVITECAN	Antibody drug conjugate	2
MURELETECAN	Unknown	2
TLC-388	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,455,174 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

12 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL84	TOPOTECAN	4	143,303
CHEMBL1607	TOPOTECAN HYDROCHLORIDE	4	56,915
CHEMBL43	AMSACRINE	4	83,286
CHEMBL53463	DOXORUBICIN	4	317,622
CHEMBL1643	RIBAVIRIN	4	78,620
CHEMBL435191	EDOTECARIN	3	1,241
CHEMBL273862	HYDROXYCAMPTOTHECIN	3	11,428
CHEMBL15245	YOHIMBINE	3	11,993
CHEMBL837	7-ETHYL-10-HYDROXYCAMPTOTHECIN	2	12,584
CHEMBL274070	9-AMINOCAMPTOTHECIN	2	16,263
CHEMBL8659	OLEIC ACID	2	720,000
CHEMBL11252	STALLIMYCIN	2	1,919

Clinical evidence (CIViC)

Drug × variant × indication, from 4 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

4 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
TOP1 Amplification	Cetuximab + FOLFIRI Regimen	Colorectal Cancer	Sensitivity/Response	CIViC B	EID12143
TOP1 Amplification	Irinotecan	Colorectal Cancer	Sensitivity/Response	CIViC B	EID888
TOP1 EXPRESSION	Carboplatin + Cyclophosphamide + Topotecan	Ovarian Cancer	Sensitivity/Response	CIViC B	EID910
TOP1 EXPRESSION	Irinotecan	Colorectal Cancer	Sensitivity/Response	CIViC B	EID912

CIViC curated variants (2)

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

Amplification (transcript amplification), EXPRESSION.

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

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

Variant	Association	Level	Drugs	Phenotypes
rs6072262	Toxicity	3	irinotecan

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6072262	TOP1	3	2.00	1	irinotecan

PharmGKB variant annotations

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

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs6072262	irinotecan	Toxicity	Genotype GG is associated with decreased severity of Neutropenia when treated with irinotecan in people with Colorectal Neoplasms as compared to genotype AA.	PMID:18347181

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — DNA topoisomerases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 5z [PMID: 8410981]	Inhibition	7.57	pIC50
compound 19 [PMID: 7707314]	Inhibition	7.55	pIC50

Binding affinities (BindingDB)

522 measured of 711 human assays (731 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL1813808	KD	0.296 nM
HOE-33342	KI	0.9 nM
CHEMBL1813809	KD	2.65 nM
corilagin	EC50	3.2 nM
2,10-Dihydroxy-6-({[6-(hydroxymethyl)pyridin-2-yl]methyl}amino)-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	3.3 nM
2,3,9,10-tetrafluoro-13-(5-fluoro-3,4-dihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-5,6,7,13-tetrahydrobenzo[4,5]thieno[2,3-a]pyrrolo[4,3-c]carbazole-5,7-dione	EC50	6.4 nM
NB-506 Analogue	EC50	8 nM
12-(6-aminomethyl-5,5-difluoro-3,4-dihydroxytetrahydro-2H-2-pyranyl)-2,3,9,10-tetrafluoro-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	8 nM
15-chloromethyl-8-ethyl-8-hydroxy-(8S)-2,3,8,9,12,14-hexahydro-11H-[1,4]dioxino[2,3-g]pyrano[3’,4’:6,7]indolizino[1,2-b]quinoline-9,12-dione	IC50	11 nM
12-(6-aminomethyl-5-fluoro-3,4-dihydroxytetrahydro-2H-2-pyranyl)-3,9-difluoro-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	11.2 nM
2,10-Dihydroxy-6-[(4-hydroxybenzyl)amino]-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	12 nM
3,9-difluoro-12-(5-fluoro-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	12.8 nM
14-chloromethyl-7-ethyl-7-hydroxy-(7S)-7,8,11,13-tetrahydro-10H-[1,3]dioxolo[4,5-g]pyrano[3’,4’:6,7]indolizino[1,2-b]quinoline-8,11-dione	IC50	15 nM
2,10-Dihydroxy-6-{[2-(hydroxymethyl)benzyl]amino}-13-(beta-Dglucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	16 nM
NB-506 Analogue	EC50	17 nM
2,10-Dihydroxy-6-[(quinolin-2-ylmethyl)amino]-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	17 nM
Ginsenoside Rd	EC50	17 nM
ginsenoside-Rb1	EC50	17 nM
3,9-difluoro-12-(5-fluoro-3,4-dihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	17.6 nM
2,10-Dihydroxy-6-({[3-(hydroxymethyl)pyridin-2-yl]methyl}amino)-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	19 nM
NB-506 Analogue	EC50	20 nM
2,10-Dihydroxy-6-[(quinolin-4-ylmethyl)amino]-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	20 nM
2,10-Dihydroxy-6-[(3-hydroxybenzyl)amino]-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	20 nM
CHEMBL4756086	IC50	21 nM
2,10-Dihydroxy-6-[(pyridin-4-ylmethyl)amino]-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	22 nM
2,10-Dihydroxy-6-{[3-(hydroxymethyl)benzyl]amino}-13-(beta-Dglucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	22 nM
2,10-Dihydroxy-6-({[4-(hydroxymethyl)pyridin-2-yl]methyl}amino)-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	22 nM
2,10-Dihydroxy-6-[(pyridin-3-ylmethyl)amino]-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	23 nM
CHEMBL4791048	IC50	24 nM
NB-506 Analogue	EC50	25 nM
6-(Benzylamino)-2,10-dihydroxy-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	25 nM
2,10-Dihydroxy-6-({[4-(hydroxymethyl)pyridin-3-yl]methyl}amino)-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	25 nM
NB-506 Analogue	EC50	26 nM
2,10-Dihydroxy-6-({[5-(hydroxymethyl)pyridin-2-yl]methyl}amino)-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	27 nM
9-Bromo-4-ethyl-4-hydroxy-11-methyl-1,12-dihydro-4H-2-oxa-6,8,12a-triaza-dibenzo[b,h]fluorene-3,13-dione	IC50	28 nM
2,10-Dihydroxy-6-({[3-(hydroxymethyl)pyridin-4-yl]methyl}amino)-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	29 nM
NB-506 Analogue	EC50	30 nM
6-[(3-Furylmethyl)amino]-2,10-dihydroxy-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	30 nM
2,10-Dihydroxy-6-[(1H-pyrrol-2-ylmethyl)amino]-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	30 nM
2,10-Dihydroxy-6-[(pyridin-2-ylmethyl)amino]-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	30 nM
2,10-Dihydroxy-6-[(quinolin-3-ylmethyl)amino]-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	30 nM
2,10-Dihydroxy-6-({[6-(hydroxymethyl)pyridin-3-yl]methyl}amino)-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	30 nM
2,10-Dihydroxy-6-({[2-(hydroxymethyl)pyridin-4-yl]methyl}amino)-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	31 nM
CHEMBL4786201	IC50	31 nM
NB-506 Analogue	EC50	32 nM
2,10-difluoro-12-(5-fluoro-3,4-dihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	32 nM
(S)-4,11-Diethyl-4-hydroxy-3,13-dioxo-3,4,12,13-tetrahydro-1H-2-oxa-6,8,12a-triaza-dibenzo[b,h]fluorene-9-carboxamidine	IC50	33 nM
2,10-Dihydroxy-6-{[4-(hydroxymethyl)benzyl]amino}-13-(beta-D-glucopyranosyl)-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	EC50	34 nM

ChEMBL bioactivities

383 potent at pChembl≥5 of 545 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.53	Kd	0.296	nM	CHEMBL1813808
8.58	Kd	2.65	nM	CHEMBL1813809
8.48	EC50	3.3	nM	CHEMBL474561
8.19	Kd	6.526	nM	CHEMBL5653589
8.19	ED50	6.526	nM	CHEMBL5653589
8.10	EC50	8	nM	CHEMBL135492
7.96	IC50	11	nM	CHEMBL338843
7.92	EC50	12	nM	CHEMBL507686
7.82	IC50	15	nM	CHEMBL335455
7.80	EC50	16	nM	CHEMBL503051
7.77	EC50	17	nM	CHEMBL447826
7.77	EC50	17	nM	CHEMBL133209
7.77	EC50	17	nM	CHEMBL135491
7.72	EC50	19	nM	CHEMBL478720
7.70	EC50	20	nM	CHEMBL452445
7.70	EC50	20	nM	CHEMBL505815
7.70	EC50	20	nM	CHEMBL135881
7.68	IC50	21	nM	TOPOTECAN
7.66	EC50	22	nM	CHEMBL455328
7.66	EC50	22	nM	CHEMBL449831
7.66	EC50	22	nM	CHEMBL446276
7.64	EC50	23	nM	CHEMBL510006
7.62	IC50	24	nM	CHEMBL4791048
7.60	IC50	25	nM	CAMPTOTHECIN
7.60	EC50	25	nM	CHEMBL454734
7.60	EC50	25	nM	CHEMBL502679
7.60	EC50	25	nM	CHEMBL334337
7.58	EC50	26	nM	CHEMBL334869
7.58	EC50	26	nM	CHEMBL338966
7.58	Kd	26.5	nM	TOPOTECAN
7.57	EC50	27	nM	CHEMBL507295
7.57	IC50	27	nM	CHEMBL307794
7.55	IC50	28	nM	CHEMBL13935
7.54	IC50	29	nM	CHEMBL4454135
7.54	EC50	29	nM	CHEMBL509544
7.52	IC50	30	nM	CHEMBL286882
7.52	EC50	30	nM	CHEMBL500059
7.52	EC50	30	nM	CHEMBL503252
7.52	EC50	30	nM	CHEMBL475683
7.52	EC50	30	nM	CHEMBL450991
7.52	EC50	30	nM	CHEMBL448760
7.52	IC50	30	nM	CHEMBL307794
7.52	EC50	30	nM	CHEMBL135970
7.51	EC50	31	nM	CHEMBL507006
7.50	EC50	32	nM	CHEMBL132533
7.48	IC50	33	nM	CHEMBL13349
7.47	EC50	34	nM	CHEMBL117315
7.46	EC50	35	nM	CHEMBL506902
7.46	EC50	35	nM	CHEMBL508108
7.43	EC50	37	nM	CHEMBL323394

PubChem BioAssay actives

311 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
(19S)-19-ethyl-19-hydroxy-10-[(2-methylphenyl)iminomethyl]-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione	610760: Binding affinity to topoisomerase 1	kd	0.0003	uM
6,20-dihydroxy-13-[[6-(hydroxymethyl)-2-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0033	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149635: Binding affinity to human TOP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0065	uM
3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0080	uM
(18S)-2-(chloromethyl)-18-ethyl-18-hydroxy-6,9,20-trioxa-13,24-diazahexacyclo[12.11.0.03,12.05,10.015,24.017,22]pentacosa-1,3,5(10),11,13,15,17(22)-heptaene-19,23-dione	56570: Inhibition of topoisomerase I activity was determined in vitro by using the cleavable complex assay(calf thymus)	ic50	0.0110	uM
6,20-dihydroxy-13-[(4-hydroxyphenyl)methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0120	uM
(5S)-14-(chloromethyl)-5-ethyl-5-hydroxy-7,18,20-trioxa-11,24-diazahexacyclo[11.11.0.02,11.04,9.015,23.017,21]tetracosa-1(24),2,4(9),13,15,17(21),22-heptaene-6,10-dione	56570: Inhibition of topoisomerase I activity was determined in vitro by using the cleavable complex assay(calf thymus)	ic50	0.0150	uM
6,20-dihydroxy-13-[[2-(hydroxymethyl)phenyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0160	uM
3-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0170	uM
3-[(2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0170	uM
6,20-dihydroxy-13-(quinolin-2-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0170	uM
6,20-dihydroxy-13-[[3-(hydroxymethyl)-2-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0190	uM
3-[(2R,3R,4S,5S)-5-(1,2-dihydroxyethyl)-3,4-dihydroxyoxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0200	uM
6,20-dihydroxy-13-(quinolin-4-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0200	uM
6,20-dihydroxy-13-[(3-hydroxyphenyl)methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0200	uM
6,20-dihydroxy-13-(pyridin-4-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0220	uM
6,20-dihydroxy-13-[[3-(hydroxymethyl)phenyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0220	uM
6,20-dihydroxy-13-[[4-(hydroxymethyl)-2-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0220	uM
6,20-dihydroxy-13-(pyridin-3-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0230	uM
6-(4-aminophenyl)-N-(3-imidazol-1-ylpropyl)-3-(1,3,4-oxadiazol-2-yl)quinolin-4-amine	1740932: Inhibition of recombinant human Top1 expressed in baculovirus infected sf9 insect cells using supercoiled pBS (SK+) DNA as substrate incubated for 30 mins by ethidium bromide staining based agarose gel electrophoresis analysis	ic50	0.0240	uM
13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0250	uM
(19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione	1544048: Poison activity at recombinant human TOP1 expressed in baculovirus infected Sf9 insect cells assessed as decrease in relaxed supercoiled pBS(SK+) DNA mobility measured after 30 mins by ethidium bromide staining based agarose gel electrophoresis	ic50	0.0250	uM
13-(benzylamino)-6,20-dihydroxy-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0250	uM
6,20-dihydroxy-13-[[4-(hydroxymethyl)-3-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0250	uM
13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0260	uM
13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3-[(2R,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0260	uM
6,20-dihydroxy-13-[[5-(hydroxymethyl)-2-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0270	uM
(19S)-7-bromo-19-ethyl-19-hydroxy-10-methyl-17-oxa-3,6,13-triazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione	56561: Inhibitory activity against DNA topoisomerase I	ic50	0.0280	uM
N-(3-imidazol-1-ylpropyl)-6-(4-methoxyphenyl)-3-(1,3,4-oxadiazol-2-yl)quinolin-4-amine	1544048: Poison activity at recombinant human TOP1 expressed in baculovirus infected Sf9 insect cells assessed as decrease in relaxed supercoiled pBS(SK+) DNA mobility measured after 30 mins by ethidium bromide staining based agarose gel electrophoresis	ic50	0.0290	uM
6,20-dihydroxy-13-[[3-(hydroxymethyl)-4-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0290	uM
3-[(2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0300	uM
6,20-dihydroxy-3-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	241607: Inhibition of topoisomerase I-DNA complex in trapping assay	ic50	0.0300	uM
13-(furan-3-ylmethylamino)-6,20-dihydroxy-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0300	uM
6,20-dihydroxy-13-(1H-pyrrol-2-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0300	uM
6,20-dihydroxy-13-(pyridin-2-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0300	uM
6,20-dihydroxy-13-(quinolin-3-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0300	uM
6,20-dihydroxy-13-[[6-(hydroxymethyl)-3-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0300	uM
6,20-dihydroxy-13-[[2-(hydroxymethyl)-4-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0310	uM
3-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0320	uM
(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,6,13-triazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-7-carboximidamide	56575: Minimum concentration that produced 50% fragmentation of DNA was measured in the presence of excess calf thymus topoisomerase.	ic50	0.0330	uM
6,20-dihydroxy-13-[[4-(hydroxymethyl)phenyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0340	uM
6,20-dihydroxy-13-(pyrazin-2-ylmethylamino)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0350	uM
6,20-dihydroxy-13-[[5-(hydroxymethyl)-3-pyridinyl]methylamino]-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0350	uM
13-(1,3-dihydroxypropan-2-ylamino)-6,19-dihydroxy-3-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211098: In vitro inhibition of Topoisomerase I-mediated DNA cleavage using supercoiled pBR322 plasmid DNA.	ec50	0.0370	uM
(19S)-19-ethyl-19-hydroxy-8-methyl-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione	210946: Inhibition of Topoisomerase I by cleavage complex formation in human HL-60 cells	ic50	0.0380	uM
5-ethyl-5-hydroxy-7,18,20-trioxa-11,24-diazahexacyclo[11.11.0.02,11.04,9.015,23.017,21]tetracosa-1(13),2,4(9),14,16,21,23-heptaene-6,10-dione	210947: Inhibition of Topoisomerase I by cleavage complex formation in intact human HL-60 cells	ic50	0.0380	uM
13-(furan-2-ylmethylamino)-6,20-dihydroxy-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	350320: Inhibition of human DNA topoisomerase 1-mediated DNA cleavage assessed as relaxation of supercoiled pBR322 plasmid DNA after 15 mins by densitometer	ec50	0.0380	uM
6,7,19,20-tetrafluoro-23-[5-fluoro-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]-3-thia-13,23-diazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaene-12,14-dione	240097: Topoisomerase I activity for single-strand breaks in the DNA substrate	ec50	0.0400	uM
3-[(2R,3R,4R)-3,4-dihydroxyoxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0400	uM
3-[(2R,3R,4S,5R)-5-(1,2-dihydroxyethyl)-3,4-dihydroxyoxolan-2-yl]-13-(1,3-dihydroxypropan-2-ylamino)-6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione	211097: Inhibitory effect on topoisomerase-1 mediated DNA cleavage using supercoiled pBR322 plasmid DNA	ec50	0.0420	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Camptothecin	decreases activity, affects cotreatment, decreases response to substance	6
Irinotecan	decreases activity, affects response to substance, affects binding	4
bisphenol A	affects expression, decreases expression	3
Estradiol	affects expression, increases expression	3
Cadmium Chloride	decreases methylation, increases expression	3
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Fluorouracil	decreases expression, affects response to substance	2
Menthol	decreases activity, decreases expression	2
Oleanolic Acid	decreases expression, decreases activity	2
Plant Extracts	increases expression, decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Topotecan	decreases activity	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
graphene oxide	decreases expression	1
cyclocurcumin	affects binding, decreases activity	1
2,4,6-tribromophenol	increases expression	1
chloroacetaldehyde	decreases expression	1
palmatine	decreases activity	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
decabromobiphenyl ether	increases expression	1
trichostatin A	affects cotreatment, decreases expression	1
nitidine	decreases expression	1
tetrahydropalmatine	increases expression	1
afimoxifene	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
delphinidin	decreases activity	1
sodium arsenite	increases abundance, increases expression	1
tetrabromobisphenol A	increases expression	1

ChEMBL screening assays

1200 unique, capped per target: 1161 binding, 38 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000097	Binding	Inhibition of topoisomerase 1-mediated relaxation of supercoiled DNA assessed as DNA cleavage at 9 uM relative to control	Cytotoxic pyrroloiminoquinones from four new species of South African latrunculid sponges. — *J Nat Prod*
CHEMBL3266692	ADMET	Inhibition of human topoisomerase 1-mediated pHOT-1 DNA relaxation at 10 to 150 uM treated with pHOT-1 substrate for 15 mins prior to enzyme addition for 30 mins by agarose gel electrophoresis	Haloemodin as novel antibacterial agent inhibiting DNA gyrase and bacterial topoisomerase I. — *J Med Chem*
CHEMBL663638	Functional	Concentration that produces 50% DNA cleavage mediated by DNA topoisomerase I	Modification of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity. — *J Med Chem*

Cellosaurus cell lines

17 cell lines: 17 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2878	CPT-K5	Cancer cell line	Female
CVCL_A787	PC-7/CPT	Cancer cell line	Male
CVCL_AS75	DU145/RC0.1	Cancer cell line	Male
CVCL_B7PT	HCT116-s	Cancer cell line	Male
CVCL_B7PU	HCT116-A2	Cancer cell line	Male
CVCL_B7PV	HCT116-C8	Cancer cell line	Male
CVCL_B7PW	HCT116-G7	Cancer cell line	Male
CVCL_D639	DU145/RC1	Cancer cell line	Male
CVCL_HE09	NALM-6 TOP1(+/-)	Cancer cell line	Male
CVCL_M595	HONE-1/CPT30	Cancer cell line	Male

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TOP1 across ~30M SureChEMBL compounds — explore on Sugi Predict.