TDP1

Summary

TDP1 (tyrosyl-DNA phosphodiesterase 1, HGNC:18884) is a protein-coding gene on chromosome 14q32.11, encoding Tyrosyl-DNA phosphodiesterase 1 (Q9NUW8). DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3’-phosphodiester bond, giving rise to DNA with a free 3’ phosphate.

The protein encoded by this gene is involved in repairing stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of the phosphodiester bond between the tyrosine residue of topoisomerase I and the 3-prime phosphate of DNA. This protein may also remove glycolate from single-stranded DNA containing 3-prime phosphoglycolate, suggesting a role in repair of free-radical mediated DNA double-strand breaks. This gene is a member of the phospholipase D family and contains two PLD phosphodiesterase domains. Mutations in this gene are associated with the disease spinocerebellar ataxia with axonal neuropathy (SCAN1).

Source: NCBI Gene 55775 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 228 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 31
• Druggable target: yes — 313 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_018319

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18884
Approved symbol	TDP1
Name	tyrosyl-DNA phosphodiesterase 1
Location	14q32.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11090, SCAN1
Ensembl gene	ENSG00000042088
Ensembl biotype	protein_coding
OMIM	607198
Entrez	55775

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 26 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000335725, ENST00000393452, ENST00000393454, ENST00000545686, ENST00000553527, ENST00000553569, ENST00000553617, ENST00000553989, ENST00000554180, ENST00000554976, ENST00000555178, ENST00000555565, ENST00000555880, ENST00000556063, ENST00000556498, ENST00000556867, ENST00000557782, ENST00000894814, ENST00000894815, ENST00000894816, ENST00000894817, ENST00000894818, ENST00000894819, ENST00000894820, ENST00000935812, ENST00000935813, ENST00000935814, ENST00000935815, ENST00000935816, ENST00000935817, ENST00000935818, ENST00000953174

RefSeq mRNA: 3 — MANE Select: NM_018319 NM_001008744, NM_001330205, NM_018319

CCDS: CCDS81836, CCDS9888

Canonical transcript exons

ENST00000335725 — 17 exons

Exon	Start	End
ENSE00001349365	89956578	89956800
ENSE00001596585	90043070	90044764
ENSE00002459551	89955927	89955970
ENSE00003463056	89967367	89967422
ENSE00003465320	89980540	89980632
ENSE00003489349	89975781	89975815
ENSE00003490202	90019316	90019418
ENSE00003495239	89991917	89991983
ENSE00003509861	89971175	89971271
ENSE00003530239	89989717	89989765
ENSE00003587231	89993376	89993483
ENSE00003587808	90033106	90033214
ENSE00003597274	89966147	89966190
ENSE00003613747	89984516	89984683
ENSE00003644093	89988905	89989090
ENSE00003656623	89963108	89963673
ENSE00003687989	89985132	89985210

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 98.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1689 / max 172.4219, expressed in 1774 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140997	12.1155	1765
140998	0.6541	326
140995	0.2036	58
140996	0.1619	54
140994	0.0338	10

Top tissues by expression

267 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.72	gold quality
secondary oocyte	CL:0000655	98.34	gold quality
right testis	UBERON:0004534	89.05	gold quality
left testis	UBERON:0004533	88.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.10	gold quality
ventricular zone	UBERON:0003053	87.90	gold quality
bone marrow cell	CL:0002092	87.88	gold quality
testis	UBERON:0000473	87.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.17	gold quality
sperm	CL:0000019	86.54	gold quality
embryo	UBERON:0000922	85.60	gold quality
male germ cell	CL:0000015	84.29	gold quality
ganglionic eminence	UBERON:0004023	83.66	gold quality
mucosa of urinary bladder	UBERON:0001259	83.36	gold quality
granulocyte	CL:0000094	83.05	gold quality
adrenal tissue	UBERON:0018303	82.66	gold quality
stromal cell of endometrium	CL:0002255	82.52	gold quality
bone marrow	UBERON:0002371	82.46	gold quality
colonic epithelium	UBERON:0000397	82.22	gold quality
islet of Langerhans	UBERON:0000006	82.15	gold quality
lymph node	UBERON:0000029	82.07	gold quality
leukocyte	CL:0000738	81.96	gold quality
rectum	UBERON:0001052	81.96	gold quality
tonsil	UBERON:0002372	81.89	gold quality
cervix squamous epithelium	UBERON:0006922	81.81	gold quality
monocyte	CL:0000576	81.70	gold quality
mononuclear cell	CL:0000842	81.66	gold quality
right uterine tube	UBERON:0001302	81.62	gold quality
vermiform appendix	UBERON:0001154	81.02	gold quality
pancreatic ductal cell	CL:0002079	80.94	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting TDP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-548O-3P	99.74	69.30	2228

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Sequences nearly identical to FLJ11090 are highly homologous to the yeast TDP1 gene. Tdp1 protein cleaves the linkage between a phosphotyrosyl group and the 3’-end of DNA, and has been shown to be involved in the repair of TOP1-induced DNA damage. (PMID:10521354)
• Protein assay of expressed FLJ11090 shows that it encodes human tyrosyl-DNA phodphodiesterase (TDP1). (PMID:11572945)
• 1.69 A crystal structure of human tyrosyl-DNA phosphodiesterase (PMID:11839309)
• a role for hTdp1 in repair of free radical-mediated DNA double strand breaks bearing terminally blocked 3’ overhangs. (PMID:12023295)
• loss-of-function mutations in TDP1 may cause spinocerebellar ataxia with axonal neuropathy either by interfering with DNA transcription or by inducing apoptosis in postmitotic neurons (PMID:12244316)
• We report the three-dimensional structures of human Tdp1 bound to the phosphate transition state analogs vanadate and tungstate (PMID:12470949)
• conserved sequences and amino acids important for catalytic activity and enzyme specificity were identified (PMID:15248776)
• TDP1 is required for the repair of topoisomerase I-mediated DNA damage and may have a role in the repair of DNA damage mediated by topoisomerase II (PMID:15494395)
• The role of TDP1 in 3’-phosphoglycolate processing during in vitro end joining of DNA double-strand breaks. (PMID:15647511)
• Tdp1 only acts upon double strand breaks in vivo (PMID:15811850)
• inhibitors of Tdp1 could act synergistically with camptothecin in anticancer therapy (PMID:15920477)
• Tdp1 may function to remove a variety of 3’ adducts from DNA during DNA repair (PMID:16141202)
• TDP1 has a role in DNA single-strand break repair and neurodegeneration [review] (PMID:16775218)
• it is proposed that Tdp1 is involved in the repair of Top1 cleavage complexes associated with transcription damage in hereditary spinocerebellar ataxia with axonal neuropathy (SCAN1) cells (PMID:16935573)
• TDP1 is also required for the repair of single stranded breaks induced by ionizing radiation (IR), though not measurably for IR-induced DNA double-strand breaks (PMID:17600775)
• Data show that mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poison. (PMID:17707402)
• This study provides a direct demonstration that Tdp1 repairs Topo I covalent lesions in vivo and suggests that spinocerebellar ataxia with axonal neuropathy (SCAN1) arises from the recessive neomorphic mutation H493R. (PMID:17948061)
• TDP1 can gain access to and can process blocked 3’ termini of double-strand breaks before ends are fully sequestered by DNA-PK, as well as at a later stage after DNA-PK autophosphorylation. (PMID:19505854)
• TDP1 phosphorylation at serine residue 81 promotes cell survival and DNA repair in response to carnitine O-palmitoyltransferase-induced DNA double-strand breaks. (PMID:19851285)
• The interaction with Lig3alpha is promoted by serine 81 that is located within a putative S/TQ site in the N-terminus domain of TDP1. (PMID:20009512)
• results suggest human Tdp1 may act using a scanning mechanism, in which Tdp1 bind non-specifically upstream of a 3’-blocking lesion and is preferentially stabilized at 3’-DNA ends corresponding to its site of action. (PMID:20097655)
• These findings provide evidence for TDP1 as a novel mitochondrial enzyme. (PMID:21041670)
• Study investigates substrate specificity of Tdp1; data suggest a role for Tdp1 in a new APE-independent base excision repair pathway. (PMID:21276450)
• topoisomerase 1, tyrosyl-DNA phosphodiesterase 1, and single-strand break repair modulate transcription-dependent CAG repeat contractions (PMID:21628532)
• Analysis of the active-site mechanism of tyrosyl-DNA phosphodiesterase I. (PMID:22155078)
• Our findings reveal a broad involvement of Tdp1 in DNA repair and clarify the role of human TDP1 in the repair of Top2-induced DNA damage. (PMID:22375014)
• study identifies TDP1 as a target for modification by the small ubiquitin-like modifier SUMO and provides evidence implicating SUMOylation in facilitating TDP1 cellular function during single-strand break repair (PMID:22415824)
• These studies suggest that one role of cytoplasmic Tdp1 is the repair of mitochondrial DNA lesions arising from oxidative stress. (PMID:23536040)
• A polymorphism at position rs28365054 in the TDP1 gene had a significant difference (P < 0.05) in the genotype distributions between the Tourette syndrome patients and the control group (PMID:23852793)
• marked overexpression of TDP1 protein and mRNA in rhabdomyosarcoma tumors was observed; results suggest a compensatory role for TDP1 in rhabdomyosarcoma after topoisomerase-I based therapy (PMID:23913164)
• TDP1 and APTX take part in the mitochondrial DNA repair and are apparently being transported from the cell nucleus. (Review) (PMID:24161509)
• Results show Tdp1 catalyzes hydrolysis of apurinic/apyrimidinic site analog correlates with the DNA helix distortion induced by the substituent. (PMID:24183900)
• TDP1 deficiency sensitizes human cells to base damage, independently of apurinic/apyrimidinic endonuclease I (APE1). (PMID:24335147)
• Data provides insights into the possible inactivation of TDP1 in cancers and its relationship to cellular response to Top1-targeted drugs. (PMID:24355542)
• This article summarizes and compares the biochemistry, functions, and post-translational regulation of TDP1 and TDP2, as well as the relevance of TDP1 and TDP2 as determinants of response to anticancer agents (PMID:24856239)
• varying expression levels of TOP1 and TDP1 polypeptides in multiple colorectal cancer cell lines and in clinical colorectal cancer samples, are reported. (PMID:25522766)
• These findings suggest that the flexibility of Tdp1 active site residues may impair the resolution of mutant Tdp1 covalent phosphohistidyl intermediates (PMID:25609251)
• TDP1 plays a role during the early stages of mammalian NHEJ. TPD1 stimulated DNA binding by XLF. TDP1 also promoted DNA binding by Ku70/80 and stimulated DNA-PK activity. (PMID:25841101)
• both TOP1 and TDP1 were upregulated in the tumor tissue compared to the adjacent non-tumor tissue in non-small cell lung cancer tissue (PMID:25987486)
• Density functional theory computations are used to acquire thermodynamic and kinetic data along the catalytic pathway, including the phosphoryl transfers of Tdp1 and subsequent hydrolysis. (PMID:26121557)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tdp1	ENSDARG00000073866
mus_musculus	Tdp1	ENSMUSG00000021177
rattus_norvegicus	Tdp1	ENSRNOG00000003831
drosophila_melanogaster	gkt	FBGN0260817
caenorhabditis_elegans		WBGENE00018678

Protein

Protein identifiers

Tyrosyl-DNA phosphodiesterase 1 — Q9NUW8 (reviewed: Q9NUW8)

All UniProt accessions (14): Q9NUW8, E7EPD8, G3V2F4, G3V2J6, G3V2U6, G3V3Q0, G3V4W8, G3V554, G3V5B8, G3V5F9, G3V5H9, H0YJ44, H0YJL7, Q9BRS7

UniProt curated annotations — full annotation on UniProt →

Function. DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3’-phosphodiester bond, giving rise to DNA with a free 3’ phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3’-phosphoglycolates on protruding 3’ ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3’exonuclease activity and can remove a single nucleoside from the 3’end of DNA and RNA molecules with 3’hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3’phosphate.

Subunit / interactions. Monomer.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitously expressed. Similar expression throughout the central nervous system (whole brain, amygdala, caudate nucleus, cerebellum, cerebral cortex, frontal lobe, hippocampus, medulla oblongata, occipital lobe, putamen, substantia nigra, temporal lobe, thalamus, nucleus accumbens and spinal cord) and increased expression in testis and thymus.

Post-translational modifications. Phosphorylated on serine and/or threonine residues, but not on tyrosine residues.

Disease relevance. Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 (SCAN1) [MIM:607250] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAN1 is an autosomal recessive cerebellar ataxia (ARCA) associated with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. All affected individuals have normal intelligence. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the tyrosyl-DNA phosphodiesterase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NUW8-1	1	yes
Q9NUW8-2	2

RefSeq proteins (3): NP_001008744, NP_001317134, NP_060789* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010347	Tdp1	Family

Pfam: PF06087

Enzyme classification (BRENDA):

• EC 3.1.4.1 — phosphodiesterase I (BRENDA: 46 organisms, 274 substrates, 536 inhibitors, 102 Km, 61 kcat entries)

Substrate kinetics (BRENDA)

35 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
P-NITROPHENYL PHENYLPHOSPHONATE	0.31–202	14
P-NITROPHENYLTHYMIDINE 5’-PHOSPHATE	0.043–6	14
BIS(4-NITROPHENYL)PHOSPHATE	1.2–22.2	9
P-NITROPHENYL ETHYL PHOSPHATE	1.7–73	9
BIS(P-NITROPHENYL) PHOSPHATE	0.25–14.4	6
BIS-P-NITROPHENYL PHOSPHATE	0.15–18.3	6
(5’-GATCTAAAAGACTT-3’)-PHOSPHOTYROSINE	0.0011–0.0048	4
DIADENOSINE 5’,5’’’-P1,P3-TRIPHOSPHATE	0.001–0.011	3
DIADENOSINE 5’,5’’’-P1,P4-TETRAPHOSPHATE	0.0006–0.008	3
P-NITROPHENYL 5’-THYMIDINE MONOPHOSPHATE	0.035–0.281	3
4-METHYLUMBELLIFERYL PHENYLPHOSPHONATE	4.9–8.2	2
4-METHYLUMBELLIFERYL THYMIDINE 5’-PHOSPHATE	0.22–2	2
4-NITROPHENYL URIDINE 5’-PHOSPHATE	0.19–0.41	2
NAD+	0.0096–0.03	2
P-NITROPHENYLPHOSPHORYLCHOLINE	1.53–3.33	2

UniProt features (83 total): strand 24, helix 21, mutagenesis site 11, sequence variant 8, turn 4, modified residue 3, region of interest 2, splice variant 2, active site 2, sequence conflict 2, binding site 2, chain 1, site 1

Structure

Experimental structures (PDB)

48 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6N0D	X-RAY DIFFRACTION	1.45
6N0N	X-RAY DIFFRACTION	1.48
6W7J	X-RAY DIFFRACTION	1.49
6N19	X-RAY DIFFRACTION	1.5
6N0R	X-RAY DIFFRACTION	1.54
7UFZ	X-RAY DIFFRACTION	1.56
7UFY	X-RAY DIFFRACTION	1.58
8V0C	X-RAY DIFFRACTION	1.62
9B3B	X-RAY DIFFRACTION	1.62
6DHU	X-RAY DIFFRACTION	1.63
6N17	X-RAY DIFFRACTION	1.64
8CVQ	X-RAY DIFFRACTION	1.65
8V0B	X-RAY DIFFRACTION	1.65
6MYZ	X-RAY DIFFRACTION	1.66
6DJF	X-RAY DIFFRACTION	1.67
1JY1	X-RAY DIFFRACTION	1.69
1RFF	X-RAY DIFFRACTION	1.7
6W7K	X-RAY DIFFRACTION	1.7
6DJE	X-RAY DIFFRACTION	1.71
6DJJ	X-RAY DIFFRACTION	1.74
6DJI	X-RAY DIFFRACTION	1.75
6DJD	X-RAY DIFFRACTION	1.78
6DIE	X-RAY DIFFRACTION	1.78
6DIH	X-RAY DIFFRACTION	1.78
6DIM	X-RAY DIFFRACTION	1.81
8CW2	X-RAY DIFFRACTION	1.81
6W4R	X-RAY DIFFRACTION	1.82
8UV1	X-RAY DIFFRACTION	1.83
8UZV	X-RAY DIFFRACTION	1.85
6MJ5	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUW8-F1	81.20	0.70

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 (3): 263 (nucleophile); 493 (proton donor/acceptor); 518 (interaction with dna)

Ligand- & substrate-binding residues (2): 265; 495

Post-translational modifications (3): 148, 61, 147

Mutagenesis-validated functional residues (11):

Position	Phenotype
263	loss of activity.
265	abolishes hydrolysis of the covalent intermediate between the active site nucleophile and dna.
265	reduces the activity to nearly undetectable levels.
283	no effect.
294	slightly reduced hydrolysis of the covalent intermediate between the active site nucleophile and dna.
493	3000-fold reduction in activity; abolishes hydrolysis of the covalent intermediate between the active site nucleophile a
493	15000-fold reduction in activity.
495	abolishes hydrolysis of the covalent intermediate between the active site nucleophile and dna.
495	125-fold reduction in activity.
516	reduced hydrolysis of the covalent intermediate between the active site nucleophile and dna.
538	abolishes hydrolysis of the covalent intermediate between the active site nucleophile and dna.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)

MSigDB gene sets: 257 (showing top): MODULE_255, GOMF_NUCLEASE_ACTIVITY, GEORGES_CELL_CYCLE_MIR192_TARGETS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MODULE_317, KAUFFMANN_DNA_REPAIR_GENES, GOBP_REGULATION_OF_DNA_REPAIR, FISCHER_G2_M_CELL_CYCLE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, AACTTT_UNKNOWN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, FISCHER_DREAM_TARGETS, REACTOME_DNA_REPAIR

GO Biological Process (4): single strand break repair (GO:0000012), DNA repair (GO:0006281), double-strand break repair (GO:0006302), DNA damage response (GO:0006974)

GO Molecular Function (8): double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), exonuclease activity (GO:0004527), 3’-tyrosyl-DNA phosphodiesterase activity (GO:0017005), nuclease activity (GO:0004518), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
DNA Double-Strand Break Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	2
DNA binding	2
cellular anatomical structure	2
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
tyrosyl-DNA phosphodiesterase activity	1
catalytic activity, acting on a nucleic acid	1
binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1554 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TDP1	TOP1	P11387	978
TDP1	XRCC1	P18887	964
TDP1	LIG3	P49916	955
TDP1	PNKP	Q96T60	920
TDP1	TDP2	O95551	913
TDP1	APTX	Q7Z2E3	912
TDP1	PARP1	P09874	889
TDP1	APEX1	P27695	860
TDP1	POLB	P06746	787
TDP1	TOP2A	P11388	742
TDP1	SPRTN	Q9H040	715
TDP1	MUS81	Q96NY9	711
TDP1	OGG1	P78554	710
TDP1	FEN1	P39748	692
TDP1	TOP1MT	Q969P6	689

IntAct

67 interactions, top by confidence:

A	B	Type	Score
CSNK1D	PER2	psi-mi:“MI:0914”(association)	0.810
LIG3	XRCC1	psi-mi:“MI:0914”(association)	0.740
TDP1	XRCC1	psi-mi:“MI:0914”(association)	0.670
TDP1	XRCC1	psi-mi:“MI:0915”(physical association)	0.670
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
TDP1	POLB	psi-mi:“MI:0914”(association)	0.640
	TDP1	psi-mi:“MI:0915”(physical association)	0.560
TDP1	TERF2	psi-mi:“MI:0915”(physical association)	0.560
BAG6	TDP1	psi-mi:“MI:0915”(physical association)	0.560
TDP1	PIAS1	psi-mi:“MI:0915”(physical association)	0.560
RASSF1	TDP1	psi-mi:“MI:0915”(physical association)	0.560
RYBP	TDP1	psi-mi:“MI:0915”(physical association)	0.560
TDP1	RNF111	psi-mi:“MI:0915”(physical association)	0.560
VAC14	TDP1	psi-mi:“MI:0915”(physical association)	0.560
MKL1	TDP1	psi-mi:“MI:0915”(physical association)	0.560
DCLRE1B	TDP1	psi-mi:“MI:0915”(physical association)	0.560
LDHAL6B	TDP1	psi-mi:“MI:0915”(physical association)	0.560
SPATA2L	TDP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (57): TDP1 (Affinity Capture-RNA), NUP153 (Affinity Capture-MS), TDP1 (Affinity Capture-MS), TDP1 (Affinity Capture-MS), TDP1 (Co-fractionation), VCP (Co-fractionation), TDP1 (Affinity Capture-MS), TDP1 (Affinity Capture-MS), TDP1 (Affinity Capture-MS), TDP1 (Affinity Capture-MS), TDP1 (Affinity Capture-MS), LIG3 (Affinity Capture-Western), TDP1 (Synthetic Lethality), TDP1 (Proximity Label-MS), LIG3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PRR9, A2AP18, D4A1F2, E7F9T0, F1MF74, F1RA39, F6QZ15, O00418, O88509, O94851, P0DOY1, P51432, P52701, P54276, Q02395, Q08BR4, Q08D35, Q1LZ50, Q2VPA6, Q3MIF2, Q3UWM4, Q4G056, Q4KLT3, Q4KWH5, Q4KWH8, Q5BJT6, Q5R7T9, Q5RGE5, Q5RHD1, Q5SGD7, Q62688, Q6INA9, Q6ZMT4, Q7Z569, Q8BGE5, Q8BJ37, Q8BMA3, Q8BML1, Q8IYD8, Q99JE6

Diamond homologs: Q4G056, Q8BJ37, Q8H1D9, Q9NUW8, Q9TXV7, Q9VQM4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATM	up-regulates	TDP1	phosphorylation
PRKDC	up-regulates	TDP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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.

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair via nonhomologous end joining	5	54.0×	6e-06
double-strand break repair	7	36.4×	3e-07
DNA repair	6	9.8×	1e-03
DNA damage response	7	9.6×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	126
Likely benign	21
Benign	53

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
3424	NM_018319.4(TDP1):c.1478A>G (p.His493Arg)	Pathogenic
687253	GRCh37/hg19 14q32.11(chr14:90476972-90505856)x1	Pathogenic
1030645	NM_018319.4(TDP1):c.910C>T (p.Arg304Ter)	Likely pathogenic
4845733	NM_018319.4(TDP1):c.629G>A (p.Trp210Ter)	Likely pathogenic
586806	NM_018319.4(TDP1):c.1731_1753+646del	Likely pathogenic

SpliceAI

3309 predictions. Top by Δscore:

Variant	Effect	Δscore
14:89963672:GG:G	donor_gain	1.0000
14:89963673:GG:G	donor_gain	1.0000
14:89967365:A:AG	acceptor_gain	1.0000
14:89967366:G:GA	acceptor_gain	1.0000
14:89980631:GG:G	donor_gain	1.0000
14:89980632:GG:G	donor_gain	1.0000
14:89984684:G:GG	donor_gain	1.0000
14:89985130:A:AG	acceptor_gain	1.0000
14:89985130:AGT:A	acceptor_gain	1.0000
14:89985131:G:GC	acceptor_gain	1.0000
14:89985131:GT:G	acceptor_gain	1.0000
14:89985131:GTG:G	acceptor_gain	1.0000
14:89985131:GTGT:G	acceptor_gain	1.0000
14:89985170:G:GT	donor_gain	1.0000
14:89985206:AGAAG:A	donor_loss	1.0000
14:89985207:GAAG:G	donor_gain	1.0000
14:89985207:GAAGG:G	donor_loss	1.0000
14:89985208:AAGGT:A	donor_loss	1.0000
14:89985210:GGT:G	donor_loss	1.0000
14:89985211:GTAAC:G	donor_loss	1.0000
14:89985212:T:G	donor_loss	1.0000
14:89988903:A:AG	acceptor_gain	1.0000
14:89988904:G:GG	acceptor_gain	1.0000
14:89989089:TGGTG:T	donor_loss	1.0000
14:89989091:G:T	donor_loss	1.0000
14:89989092:TGAGT:T	donor_loss	1.0000
14:89989093:GAG:G	donor_loss	1.0000
14:89991984:G:GG	donor_gain	1.0000
14:89993372:CTA:C	acceptor_loss	1.0000
14:89993374:A:AG	acceptor_gain	1.0000

AlphaMissense

4023 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:89975799:T:C	F259L	1.000
14:89975801:T:A	F259L	1.000
14:89975801:T:G	F259L	1.000
14:89975803:G:A	G260E	1.000
14:89980542:A:T	K265I	1.000
14:89980597:C:A	N283K	1.000
14:89980597:C:G	N283K	1.000
14:89988971:A:C	S400R	1.000
14:89988973:C:A	S400R	1.000
14:89988973:C:G	S400R	1.000
14:89988978:G:A	G402D	1.000
14:89989742:G:C	R448P	1.000
14:89993380:T:A	W480R	1.000
14:89993380:T:C	W480R	1.000
14:89993427:G:C	K495N	1.000
14:89993427:G:T	K495N	1.000
14:90019322:T:A	N516K	1.000
14:90019322:T:G	N516K	1.000
14:90019338:T:A	W522R	1.000
14:90019338:T:C	W522R	1.000
14:90019342:G:A	G523E	1.000
14:90043078:T:A	W588R	1.000
14:90043078:T:C	W588R	1.000
14:89967372:C:A	N203K	0.999
14:89967372:C:G	N203K	0.999
14:89975802:G:A	G260R	0.999
14:89975802:G:C	G260R	0.999
14:89975803:G:T	G260V	0.999
14:89975811:C:G	H263D	0.999
14:89975813:C:A	H263Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000005708 (14:89957008 C>G), RS1000037130 (14:89956809 A>C), RS1000057625 (14:90002529 TTA>T), RS1000143681 (14:89981822 A>G), RS1000150685 (14:89989819 C>A,G,T), RS1000175609 (14:89990115 T>A), RS1000208133 (14:89978915 T>C), RS1000253322 (14:90044787 C>T), RS1000288863 (14:89983940 C>G,T), RS1000302025 (14:90020681 G>T), RS1000324333 (14:89966840 C>T), RS1000374550 (14:89960058 C>T), RS1000407806 (14:90027121 C>G,T), RS1000425277 (14:89996816 C>A), RS1000454061 (14:90020353 T>G)

Disease associations

OMIM: gene MIM:607198 | disease phenotypes: MIM:607250

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1	Strong	Autosomal recessive
male infertility with azoospermia or oligozoospermia due to single gene mutation	Disputed Evidence	Autosomal recessive

Mondo (3): spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 (MONDO:0011801), myoepithelial tumor (MONDO:0002380), (MONDO:0018393)

Orphanet (1): Spinocerebellar ataxia with axonal neuropathy type 1 (Orphanet:94124)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000640	Gaze-evoked nystagmus
HP:0000763	Sensory neuropathy
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001761	Pes cavus
HP:0002059	Cerebral atrophy
HP:0002166	Impaired vibration sensation in the lower limbs
HP:0002283	Global brain atrophy
HP:0002464	Spastic dysarthria
HP:0002495	Impaired vibratory sensation
HP:0002503	Spinocerebellar tract degeneration
HP:0002936	Distal sensory impairment
HP:0003073	Hypoalbuminemia
HP:0003124	Hypercholesterolemia
HP:0003376	Steppage gait
HP:0003380	Decreased number of peripheral myelinated nerve fibers
HP:0003431	Decreased motor nerve conduction velocity
HP:0003477	Peripheral axonal neuropathy
HP:0003621	Juvenile onset
HP:0003693	Distal amyotrophy
HP:0006855	Cerebellar vermis atrophy
HP:0006858	Impaired distal proprioception
HP:0007021	Pain insensitivity
HP:0007141	Sensorimotor neuropathy
HP:0009053	Distal lower limb muscle weakness

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585
C537313	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075138 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

313 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 796,060 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1009	LEVODOPA	4	103,854
CHEMBL101	PHENYLBUTAZONE	4	59,455
CHEMBL1010	CEFOTAXIME SODIUM	4	4,928
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1057	FLUORESCEIN	4	329,940
CHEMBL1083993	AMIODARONE HYDROCHLORIDE	4	3,265
CHEMBL109	VALPROIC ACID	4	65,937
CHEMBL1091250	INDIGOTINDISULFONATE	4	340
CHEMBL1109	SULFAPHENAZOLE	4	4,065
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1116	RALOXIFENE HYDROCHLORIDE	4	28,574
CHEMBL1120	BISMUTH SUBSALICYLATE	4
CHEMBL11359	CISPLATIN	4
CHEMBL119	TRIMETREXATE	4	57,002
CHEMBL1200326	NICARDIPINE HYDROCHLORIDE	4	3,903
CHEMBL1200348	SULCONAZOLE NITRATE	4	3,129
CHEMBL1200471	PYRITHIONE ZINC	4	24,834
CHEMBL1200474	DEMECLOCYCLINE HYDROCHLORIDE	4	1,867
CHEMBL1200479	DICYCLOMINE HYDROCHLORIDE	4	4,309
CHEMBL1200522	AVOBENZONE	4
CHEMBL1200523	CEFAZOLIN SODIUM	4
CHEMBL1200530	CEFOXITIN SODIUM	4
CHEMBL1200585	OXYMETHOLONE	4
CHEMBL1200596	CHLOROXINE	4
CHEMBL1200692	OLMESARTAN MEDOXOMIL	4
CHEMBL1200758	AMPICILLIN SODIUM	4
CHEMBL1200787	PHENOXYBENZAMINE HYDROCHLORIDE	4
CHEMBL1200836	OXICONAZOLE NITRATE	4
CHEMBL1200916	THIORIDAZINE HYDROCHLORIDE	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2401863	TDP1		0.00	0

Binding affinities (BindingDB)

30 measured of 30 human assays (30 total across all organisms); most potent 30 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4451622	IC50	3500 nM
2-[[6-(3-aminopropyl)-5,11-dioxoindeno[1,2-c]isoquinolin-3-yl]amino]acetic acid	IC50	5000 nM	US-9402842: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (Tdp1)—topoisomerase I (Top1) inhibitors
N-[6-(5,11-dioxoindeno[1,2-c]isoquinolin-6-yl)hexyl]methanesulfonamide	IC50	5200 nM	US-8912213: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (TDP1)- topoisomerase I (TOP1) inhibitors
6-(3-aminopropyl)-3-iodo-9-methoxyindeno[1,2-c]isoquinoline-5,11-dione	IC50	5200 nM	US-9402842: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (Tdp1)—topoisomerase I (Top1) inhibitors
6-(3-aminopropyl)-7-methoxy-3-nitroindeno[1,2-c]isoquinoline-5,11-dione	IC50	5800 nM	US-8912213: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (TDP1)- topoisomerase I (TOP1) inhibitors
6-(3-aminopropyl)-7-methoxy-3-nitroindeno[1,2-c]isoquinoline-5,11-dione	IC50	5800 nM	US-9402842: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (Tdp1)—topoisomerase I (Top1) inhibitors
CHEMBL2059427	IC50	6700 nM	US-8912213: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (TDP1)- topoisomerase I (TOP1) inhibitors
3-amino-6-(3-aminopropyl)-9-methoxyindeno[1,2-c]isoquinoline-5,11-dione	IC50	6700 nM	US-9402842: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (Tdp1)—topoisomerase I (Top1) inhibitors
N-[[4-[N-(diaminomethylidene)carbamimidoyl]piperazin-1-yl]methyl]-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide	IC50	9000 nM	US-8865686: Tetracycline compounds as tyrosyl-DNA phosphodiesterase I inhibitors
6-(3-aminopropyl)-9-methoxy-3-nitroindeno[1,2-c]isoquinoline-5,11-dione	IC50	11000 nM	US-8912213: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (TDP1)- topoisomerase I (TOP1) inhibitors
ethyl 2-[[6-(3-aminopropyl)-5,11-dioxoindeno[1,2-c]isoquinolin-3-yl]amino]acetate	IC50	11000 nM	US-8912213: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (TDP1)- topoisomerase I (TOP1) inhibitors
6-(3-aminopropyl)-9-methoxy-3-nitroindeno[1,2-c]isoquinoline-5,11-dione	IC50	11000 nM	US-9402842: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (Tdp1)—topoisomerase I (Top1) inhibitors
3-amino-6-(3-aminopropyl)indeno[1,2-c]isoquinoline-5,11-dione	IC50	12000 nM	US-8912213: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (TDP1)- topoisomerase I (TOP1) inhibitors
6-(3-aminopropyl)-8-methoxy-3-nitroindeno[1,2-c]isoquinoline-5,11-dione	IC50	15000 nM	US-8912213: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (TDP1)- topoisomerase I (TOP1) inhibitors
CHEMBL2057325	IC50	18000 nM	US-8912213: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (TDP1)- topoisomerase I (TOP1) inhibitors
N-[6-(3-aminopropyl)-5,11-dioxoindeno[1,2-c]isoquinolin-3-yl]acetamide	IC50	18000 nM	US-9402842: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (Tdp1)—topoisomerase I (Top1) inhibitors
methyl 3-[[6-(3-aminopropyl)-5,11-dioxoindeno[1,2-c]isoquinolin-3-yl]amino]-3-oxopropanoate	IC50	18000 nM	US-9402842: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (Tdp1)—topoisomerase I (Top1) inhibitors
CHEMBL2172218	IC50	18000 nM	US-8912213: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (TDP1)- topoisomerase I (TOP1) inhibitors
CHEMBL4435210	IC50	19300 nM
N-[[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]amino]methyl]-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide	IC50	29000 nM	US-8865686: Tetracycline compounds as tyrosyl-DNA phosphodiesterase I inhibitors
CHEMBL2057324	IC50	45000 nM	US-8912213: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (TDP1)- topoisomerase I (TOP1) inhibitors
methyl 2-[[6-(3-aminopropyl)-5,11-dioxoindeno[1,2-c]isoquinolin-3-yl]amino]-2-oxoacetate	IC50	45000 nM	US-9402842: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (Tdp1)—topoisomerase I (Top1) inhibitors
3-[[[4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carbonyl]amino]methylamino]phthalic acid	IC50	49000 nM	US-8865686: Tetracycline compounds as tyrosyl-DNA phosphodiesterase I inhibitors
(6-methyl-5,11-dioxoindeno[1,2-c]isoquinolin-3-yl)carbamic acid	IC50	61000 nM	US-8912213: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (TDP1)- topoisomerase I (TOP1) inhibitors
BDBM50425048	IC50	61000 nM	US-9402842: Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (Tdp1)—topoisomerase I (Top1) inhibitors
4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-N-(pyrrolidin-1-ylmethyl)-4,4a,5,5a-tetrahydrotetracene-2-carboxamide	IC50	84000 nM	US-8865686: Tetracycline compounds as tyrosyl-DNA phosphodiesterase I inhibitors
2-[[4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carbonyl]amino]-3-hydroxybutanoic acid	IC50	106000 nM	US-8865686: Tetracycline compounds as tyrosyl-DNA phosphodiesterase I inhibitors
4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-N-(2-hydroxyethyl)-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide	IC50	122000 nM	US-8865686: Tetracycline compounds as tyrosyl-DNA phosphodiesterase I inhibitors
6-[[4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid	IC50	141000 nM	US-8865686: Tetracycline compounds as tyrosyl-DNA phosphodiesterase I inhibitors
4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide	IC50	785000 nM	US-8865686: Tetracycline compounds as tyrosyl-DNA phosphodiesterase I inhibitors

ChEMBL bioactivities

3725 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Potency	1	nM	CIS-RESVERATROL
9.00	Potency	1	nM	CARBETAPENTANE
8.74	Potency	1.8	nM	CHEMBL1555076
8.74	Potency	1.8	nM	CICLOPIROX OLAMINE
8.74	Potency	1.8	nM	ETHAVERINE
8.74	Potency	1.8	nM	CHEMBL1398443
8.70	Potency	2	nM	CHEMBL1603234
8.70	Potency	2	nM	CHEMBL189438
8.70	Potency	2	nM	CHEMBL1356989
8.66	Potency	2.2	nM	DISOPIRAMIDE
8.60	Potency	2.5	nM	CHEMBL1451277
8.49	Potency	3.2	nM	CHEMBL1335406
8.46	Potency	3.5	nM	QUISQUALATE
8.40	Potency	4	nM	ESATENOLOL
8.40	Potency	4	nM	CHEMBL1430739
8.40	Potency	4	nM	CHEMBL1579403
8.35	Potency	4.5	nM	CHLORCYCLIZINE HYDROCHLORIDE
8.35	Potency	4.5	nM	CHEMBL1434820
8.35	Potency	4.5	nM	CHEMBL1489519
8.30	IC50	5	nM	CHEMBL4464463
8.30	Potency	5	nM	CHEMBL1502833
8.30	Potency	5	nM	ROTENONE
8.30	Potency	5	nM	CHEMBL1256914
8.30	Potency	5	nM	CHEMBL1612121
8.30	Potency	5	nM	CHEMBL1613623
8.25	Potency	5.6	nM	LUZINDOLE
8.20	Potency	6.3	nM	CHEMBL394034
8.20	Potency	6.3	nM	CHEMBL314699
8.15	Potency	7.1	nM	CHEMBL64119
8.15	Potency	7.1	nM	CHEMBL313938
8.15	Potency	7.1	nM	CHEMBL1383301
8.15	Potency	7.1	nM	N-METHYLHISTAMINE DIHYDROCHLORIDE
8.10	Potency	7.9	nM	CHEMBL1575506
8.10	Potency	7.9	nM	CHEMBL1971767
8.05	Potency	8.9	nM	SAPPANONE A DIMETHYL ETHER
8.05	Potency	8.9	nM	FLUORESCEIN
8.05	Potency	8.9	nM	HOMOVANILLIC ACID
8.05	Potency	8.9	nM	CHEMBL1348421
8.00	Potency	10	nM	AMOXAPINE
8.00	Potency	10	nM	FLUORESCEIN
8.00	Potency	10	nM	CHEMBL1608830
8.00	Potency	10	nM	CHEMBL1372222
8.00	Potency	10	nM	CHEMBL250447
7.99	IC50	10.3	nM	CHEMBL4746230
7.95	Potency	11.2	nM	MEFENAMIC ACID
7.95	Potency	11.2	nM	MINAPRINE
7.95	Potency	11.2	nM	DIMETHISOQUIN
7.95	Potency	11.2	nM	FLUORESCEIN
7.95	Potency	11.2	nM	CHEMBL3198603
7.95	Potency	11.2	nM	CHEMBL1462323

PubChem BioAssay actives

202 with measured affinity, of 1087 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
7-[4-[[4-[(4,6-dimethylpyrimidin-2-yl)sulfamoyl]anilino]methyl]piperazin-1-yl]-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid	1631088: Inhibition of recombinant TDP1 (unknown origin) using 5’-32P-labeled N14Y DNA substrate incubated for 15 mins by PAGE analysis	ic50	0.0050	uM
(9bR)-2-acetyl-6-[2-[(1E)-2,6-dimethylhepta-1,5-dienyl]-1,3-thiazol-4-yl]-3,7,9-trihydroxy-8,9b-dimethyldibenzofuran-1-one	1675246: Inhibition of recombinant TDP1 (unknown origin) expressed in Escherichia coli using 5’-FAM/3’-BHQ1 tagged oligonucleotide as substrate by fluorescence assay	ic50	0.0103	uM
5-[(3-carboxy-4-hydroxyphenyl)-(3-carboxy-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]-2-hydroxybenzoic acid	1631086: Inhibition of recombinant TDP1 (unknown origin) using 5’-32P-labeled N14Y DNA substrate incubated for 20 mins by PAGE analysis	ic50	0.0120	uM
(9bR)-2-acetyl-6-[2-[(2E)-2-(3,7-dimethyloct-6-enylidene)hydrazinyl]-1,3-thiazol-4-yl]-3,7,9-trihydroxy-8,9b-dimethyldibenzofuran-1-one	1851331: Inhibition of recombinant human TDP1 measured by real-time oligonucleotide biosensor assay	ic50	0.0160	uM
(9bR)-2-acetyl-6-[2-(2,6-dimethylhept-5-enyl)-1,3-thiazol-4-yl]-3,7,9-trihydroxy-8,9b-dimethyldibenzofuran-1-one	1675246: Inhibition of recombinant TDP1 (unknown origin) expressed in Escherichia coli using 5’-FAM/3’-BHQ1 tagged oligonucleotide as substrate by fluorescence assay	ic50	0.0164	uM
1-cyclopropyl-7-[4-[[4-[(4,6-dimethylpyrimidin-2-yl)sulfamoyl]anilino]methyl]-3-methylpiperazin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid	1631088: Inhibition of recombinant TDP1 (unknown origin) using 5’-32P-labeled N14Y DNA substrate incubated for 15 mins by PAGE analysis	ic50	0.0220	uM
(2Z,5bR)-7-acetyl-2-[(3,5-ditert-butyl-2-hydroxyphenyl)methylidene]-5,8-dihydroxy-4,5b-dimethyl-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.0250	uM
(9bR)-2-acetyl-6-[2-[(2E)-2-[(4-bromophenyl)methylidene]hydrazinyl]-1,3-thiazol-4-yl]-3,7,9-trihydroxy-8,9b-dimethyldibenzofuran-1-one	1532280: Inhibition of recombinant human full-length N-terminal His-tagged Tdp1 expressed in Escherichia coli BL21 (DE3) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 1 min for 7 mins by fluorimetric method	ic50	0.0260	uM
(9bR)-2-acetyl-3,7,9-trihydroxy-8,9b-dimethyl-6-[2-[(2Z)-2-[[(4R)-4-prop-1-en-2-ylcyclohexen-1-yl]methylidene]hydrazinyl]-1,3-thiazol-4-yl]dibenzofuran-1-one	1675246: Inhibition of recombinant TDP1 (unknown origin) expressed in Escherichia coli using 5’-FAM/3’-BHQ1 tagged oligonucleotide as substrate by fluorescence assay	ic50	0.0270	uM
(9bR)-2-acetyl-3,7,9-trihydroxy-8,9b-dimethyl-6-[2-[(2Z)-2-[(1R,4R)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanylidene]hydrazinyl]-1,3-thiazol-4-yl]dibenzofuran-1-one	1675246: Inhibition of recombinant TDP1 (unknown origin) expressed in Escherichia coli using 5’-FAM/3’-BHQ1 tagged oligonucleotide as substrate by fluorescence assay	ic50	0.0310	uM
(9bR)-2-acetyl-3,7,9-trihydroxy-8,9b-dimethyl-6-[2-[(2E)-2-[(4-nitrophenyl)methylidene]hydrazinyl]-1,3-thiazol-4-yl]dibenzofuran-1-one	1532280: Inhibition of recombinant human full-length N-terminal His-tagged Tdp1 expressed in Escherichia coli BL21 (DE3) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 1 min for 7 mins by fluorimetric method	ic50	0.0350	uM
(9bR)-2-acetyl-6-[2-[(2Z)-2-[[(1S,5R)-6,6-dimethyl-3-bicyclo[3.1.1]hept-2-enyl]methylidene]hydrazinyl]-1,3-thiazol-4-yl]-3,7,9-trihydroxy-8,9b-dimethyldibenzofuran-1-one	1675246: Inhibition of recombinant TDP1 (unknown origin) expressed in Escherichia coli using 5’-FAM/3’-BHQ1 tagged oligonucleotide as substrate by fluorescence assay	ic50	0.0450	uM
(9bR)-2-acetyl-3,7,9-trihydroxy-8,9b-dimethyl-6-[2-[2-[(1R,5R)-4,6,6-trimethyl-2-bicyclo[3.1.1]hept-3-enylidene]hydrazinyl]-1,3-thiazol-4-yl]dibenzofuran-1-one	1675246: Inhibition of recombinant TDP1 (unknown origin) expressed in Escherichia coli using 5’-FAM/3’-BHQ1 tagged oligonucleotide as substrate by fluorescence assay	ic50	0.0460	uM
(2Z,5bR)-7-acetyl-2-[(5-bromothiophen-2-yl)methylidene]-5,8-dihydroxy-4,5b-dimethyl-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.0630	uM
(2Z,5bS)-7-acetyl-2-[(3,5-ditert-butyl-2-hydroxyphenyl)methylidene]-5,8-dihydroxy-4,5b-dimethyl-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.0640	uM
(9bR)-2-acetyl-6-[2-[(2E)-2-[(4-chlorophenyl)methylidene]hydrazinyl]-1,3-thiazol-4-yl]-3,7,9-trihydroxy-8,9b-dimethyldibenzofuran-1-one	1532280: Inhibition of recombinant human full-length N-terminal His-tagged Tdp1 expressed in Escherichia coli BL21 (DE3) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 1 min for 7 mins by fluorimetric method	ic50	0.0680	uM
(2Z,5bS)-7-acetyl-2-[(5-bromothiophen-2-yl)methylidene]-5,8-dihydroxy-4,5b-dimethyl-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.0810	uM
(9bR)-2-acetyl-3,7,9-trihydroxy-8,9b-dimethyl-6-[2-[(2E)-2-[(3-nitrophenyl)methylidene]hydrazinyl]-1,3-thiazol-4-yl]dibenzofuran-1-one	1532280: Inhibition of recombinant human full-length N-terminal His-tagged Tdp1 expressed in Escherichia coli BL21 (DE3) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 1 min for 7 mins by fluorimetric method	ic50	0.0860	uM
(9bR)-2-acetyl-6-(2-hexyl-1,3-thiazol-4-yl)-3,7,9-trihydroxy-8,9b-dimethyldibenzofuran-1-one	1675246: Inhibition of recombinant TDP1 (unknown origin) expressed in Escherichia coli using 5’-FAM/3’-BHQ1 tagged oligonucleotide as substrate by fluorescence assay	ic50	0.0880	uM
1-[[(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methyl]-3-[3-[[[(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methylcarbamoylamino]methyl]-3,5,5-trimethylcyclohexyl]urea	1615660: Inhibition of recombinant TDP1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorescence based assay	ic50	0.0900	uM
7-[(2,6-dichlorophenyl)methoxy]-4-(2-oxochromen-3-yl)chromen-2-one	1653889: Inhibition of TDP1 (unknown origin) using 5’-(5,6 FAM-AAC GTC AGG GTC TTC C- BHQ1)-3’ as substrate measured for every 1 min by fluorescence based assay	ic50	0.0990	uM
1-[[(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methyl]-3-(1-adamantyl)urea	1615660: Inhibition of recombinant TDP1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorescence based assay	ic50	0.1000	uM
1-[[(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methyl]-3-[3-[[(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methylcarbamoylamino]-4-methylphenyl]urea	1615660: Inhibition of recombinant TDP1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorescence based assay	ic50	0.1100	uM
2-chloro-5-(2,5-dimethylpyrrol-1-yl)benzoic acid	1532276: Inhibition of Tdp1 (unknown origin)	ic50	0.1100	uM
(9bR)-2-acetyl-3,7,9-trihydroxy-6-[2-(6-hydroxy-2,6-dimethylheptyl)-1,3-thiazol-4-yl]-8,9b-dimethyldibenzofuran-1-one	1675246: Inhibition of recombinant TDP1 (unknown origin) expressed in Escherichia coli using 5’-FAM/3’-BHQ1 tagged oligonucleotide as substrate by fluorescence assay	ic50	0.1390	uM
(2Z,5bR)-7-acetyl-2-[(4-bromophenyl)methylidene]-5,8-dihydroxy-4,5b-dimethyl-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.1500	uM
(9bR)-2-acetyl-6-[2-[(2E)-2-[(4-fluorophenyl)methylidene]hydrazinyl]-1,3-thiazol-4-yl]-3,7,9-trihydroxy-8,9b-dimethyldibenzofuran-1-one	1532280: Inhibition of recombinant human full-length N-terminal His-tagged Tdp1 expressed in Escherichia coli BL21 (DE3) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 1 min for 7 mins by fluorimetric method	ic50	0.1500	uM
(9bR)-2-acetyl-3,7,9-trihydroxy-6-[2-[(2E)-2-[(4-methoxyphenyl)methylidene]hydrazinyl]-1,3-thiazol-4-yl]-8,9b-dimethyldibenzofuran-1-one	1532280: Inhibition of recombinant human full-length N-terminal His-tagged Tdp1 expressed in Escherichia coli BL21 (DE3) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 1 min for 7 mins by fluorimetric method	ic50	0.1580	uM
(2E)-6-acetyl-2-[1-[3-(3,5-ditert-butyl-4-hydroxyphenyl)propylamino]ethylidene]-7,9-dihydroxy-8,9b-dimethyldibenzofuran-1,3-dione	1431313: Inhibition of recombinant TDP1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured at 1 min interval by fluorimetric method	ic50	0.1600	uM
(2Z,5bR)-7-acetyl-5,8-dihydroxy-4,5b-dimethyl-2-[(5-methylfuran-2-yl)methylidene]-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.1600	uM
(9bR)-2-acetyl-6-[2-[(2E)-2-benzylidenehydrazinyl]-1,3-thiazol-4-yl]-3,7,9-trihydroxy-8,9b-dimethyldibenzofuran-1-one	1532280: Inhibition of recombinant human full-length N-terminal His-tagged Tdp1 expressed in Escherichia coli BL21 (DE3) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 1 min for 7 mins by fluorimetric method	ic50	0.1720	uM
(2E)-6-acetyl-2-[1-[2-(3,5-ditert-butyl-4-hydroxyphenyl)ethylamino]ethylidene]-7,9-dihydroxy-8,9b-dimethyldibenzofuran-1,3-dione	1431313: Inhibition of recombinant TDP1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured at 1 min interval by fluorimetric method	ic50	0.1900	uM
1-[[(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methyl]-3-[6-[[(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methylcarbamoylamino]hexyl]urea	1615660: Inhibition of recombinant TDP1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorescence based assay	ic50	0.1900	uM
(9bR)-2-acetyl-3,7,9-trihydroxy-6-[2-[(2E)-2-[(4-hydroxy-3-methoxyphenyl)methylidene]hydrazinyl]-1,3-thiazol-4-yl]-8,9b-dimethyldibenzofuran-1-one	1532280: Inhibition of recombinant human full-length N-terminal His-tagged Tdp1 expressed in Escherichia coli BL21 (DE3) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 1 min for 7 mins by fluorimetric method	ic50	0.1920	uM
2-(dibutylamino)-N-[8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-yl]acetamide	1194628: Inhibition of recombinant TDP1 (unknown origin) assessed as increase in fluorescence	ic50	0.2200	uM
(2Z,5bR)-7-acetyl-2-[(2-bromophenyl)methylidene]-5,8-dihydroxy-4,5b-dimethyl-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.2300	uM
(2Z,5bR)-7-acetyl-2-[(3-bromophenyl)methylidene]-5,8-dihydroxy-4,5b-dimethyl-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.2320	uM
(2E,9bR)-6-acetyl-2-[1-(4-bromoanilino)ethylidene]-7,9-dihydroxy-8,9b-dimethyldibenzofuran-1,3-dione	1431313: Inhibition of recombinant TDP1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured at 1 min interval by fluorimetric method	ic50	0.2600	uM
7-(naphthalen-1-ylmethoxy)-4-(2-oxochromen-3-yl)chromen-2-one	1653889: Inhibition of TDP1 (unknown origin) using 5’-(5,6 FAM-AAC GTC AGG GTC TTC C- BHQ1)-3’ as substrate measured for every 1 min by fluorescence based assay	ic50	0.2700	uM
1-[[(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methyl]-3-(4-chlorophenyl)urea	1615660: Inhibition of recombinant TDP1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorescence based assay	ic50	0.2800	uM
7-[(2-chlorophenyl)methoxy]-4-(2-oxochromen-3-yl)chromen-2-one	1653889: Inhibition of TDP1 (unknown origin) using 5’-(5,6 FAM-AAC GTC AGG GTC TTC C- BHQ1)-3’ as substrate measured for every 1 min by fluorescence based assay	ic50	0.2800	uM
(2Z,5bR)-7-acetyl-5,8-dihydroxy-2-[(4-methoxyphenyl)methylidene]-4,5b-dimethyl-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.3400	uM
(2Z,5bR)-7-acetyl-5,8-dihydroxy-4,5b-dimethyl-2-[(2,3,4-trimethoxyphenyl)methylidene]-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.3400	uM
N-(3,4-dihydroxyphenyl)-N-methylnitrous amide	1532277: Inhibition of recombinant human Tdp1 using 5’-biotin-GATCTAAAAGACTT-pY-3’ as substrate measured after 20 mins by AlphaScreen assay	ic50	0.3600	uM
7-[(4-chlorophenyl)methoxy]-4-(8-methoxy-2-oxochromen-3-yl)-8-methylchromen-2-one	1653889: Inhibition of TDP1 (unknown origin) using 5’-(5,6 FAM-AAC GTC AGG GTC TTC C- BHQ1)-3’ as substrate measured for every 1 min by fluorescence based assay	ic50	0.3600	uM
(2Z,5bR)-7-acetyl-5,8-dihydroxy-2-[(2-methoxyphenyl)methylidene]-4,5b-dimethyl-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.3900	uM
(2Z,5bR)-7-acetyl-5,8-dihydroxy-4,5b-dimethyl-2-(pyridin-3-ylmethylidene)-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.4500	uM
(9bR)-2-acetyl-3,7,9-trihydroxy-6-[2-[(2E)-2-[(4-hydroxyphenyl)methylidene]hydrazinyl]-1,3-thiazol-4-yl]-8,9b-dimethyldibenzofuran-1-one	1532280: Inhibition of recombinant human full-length N-terminal His-tagged Tdp1 expressed in Escherichia coli BL21 (DE3) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 1 min for 7 mins by fluorimetric method	ic50	0.4570	uM
1-[[(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methyl]-3-cyclohexylurea	1615660: Inhibition of recombinant TDP1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorescence based assay	ic50	0.5000	uM
(2Z,5bR)-7-acetyl-2-[(3,5-dibromophenyl)methylidene]-5,8-dihydroxy-4,5b-dimethyl-[1]benzofuro[4,5-b][1]benzofuran-1,6-dione	1398692: Inhibition of recombinant Tdp1 (unknown origin) using 5’-(5,6 FAM-aac gtc agg gtc ttc c-BHQ1)-3’ as substrate measured every 55 secs for 8 mins by fluorimetric assay	ic50	0.5300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Cisplatin	decreases response to substance, increases expression	2
Lead	affects expression, decreases expression	2
Cadmium Chloride	decreases expression	2
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression, increases expression	1
manganese chloride	increases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
myrtenal	decreases activity	1
2-aminoadamantane	decreases activity	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
citronellal	decreases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
veliparib	decreases reaction, increases expression, increases reaction	1
(+)-JQ1 compound	decreases expression	1

ChEMBL screening assays

109 unique, capped per target: 105 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1068068	Binding	Inhibition of human tyrosyl-DNA phosphodiesterase 1 after 30 mins by alpha high throughput screening assay	Inhibitors of human tyrosyl-DNA phospodiesterase (hTdp1) developed by virtual screening using ligand-based pharmacophores. — Bioorg Med Chem
CHEMBL1738394	Functional	PUBCHEM_BIOASSAY: Confirmation Assay for Inhibitors of Tyrosyl-DNA Phosphodiesterase (TDP1). (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID485290, AID485312, AID504464, AID504474]	PubChem BioAssay data set

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C1NB	SNU-601 Ola-R	Cancer cell line	Male
CVCL_D1QW	Abcam K-562 TDP1 KO	Cancer cell line	Female
CVCL_D2MH	Abcam Raji TDP1 KO	Cancer cell line	Male
CVCL_TR83	HAP1 TDP1 (-) 1	Cancer cell line	Male
CVCL_TR84	HAP1 TDP1 (-) 2	Cancer cell line	Male
CVCL_TR85	HAP1 TDP1 (-) 3	Cancer cell line	Male
CVCL_WQ65	Abcam Jurkat TDP1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

6 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis