TNKS

Summary

TNKS (tankyrase, HGNC:11941) is a protein-coding gene on chromosome 8p23.1, encoding Poly [ADP-ribose] polymerase tankyrase-1 (O95271). Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking.

Enables histone binding activity; pentosyltransferase activity; and zinc ion binding activity. Involved in several processes, including positive regulation of canonical Wnt signaling pathway; post-translational protein modification; and regulation of chromosome organization. Acts upstream of or within peptidyl-serine phosphorylation and peptidyl-threonine phosphorylation. Located in several cellular components, including chromosome, telomeric region; mitotic spindle pole; and nucleus.

Source: NCBI Gene 8658 — RefSeq curated summary.

At a glance

• GWAS associations: 81
• Clinical variants (ClinVar): 208 total
• Druggable target: yes — 9 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003747

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11941
Approved symbol	TNKS
Name	tankyrase
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	TIN1, TINF1, TNKS1, PARP-5a, PARP5A, pART5, ARTD5
Ensembl gene	ENSG00000173273
Ensembl biotype	protein_coding
OMIM	603303
Entrez	8658

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000310430, ENST00000517770, ENST00000517989, ENST00000518027, ENST00000518281, ENST00000518635, ENST00000519191, ENST00000519392, ENST00000519930, ENST00000520408, ENST00000521039, ENST00000522110, ENST00000885810, ENST00000885812

RefSeq mRNA: 1 — MANE Select: NM_003747 NM_003747

CCDS: CCDS5974

Canonical transcript exons

ENST00000310430 — 27 exons

Exon	Start	End
ENSE00001184221	9770106	9770262
ENSE00001184225	9766239	9766425
ENSE00001184227	9765692	9765797
ENSE00001184230	9764716	9764790
ENSE00001184232	9763147	9763244
ENSE00001184234	9761516	9761636
ENSE00001184236	9752544	9752626
ENSE00001184239	9751609	9751846
ENSE00001184247	9735377	9735486
ENSE00001184256	9733279	9733444
ENSE00001184259	9730890	9731035
ENSE00001184272	9710142	9710220
ENSE00001184274	9709955	9710046
ENSE00001184276	9708371	9708492
ENSE00001217782	9720374	9720545
ENSE00001326665	9776650	9782346
ENSE00001621845	9734865	9735084
ENSE00003465347	9580159	9580383
ENSE00003534852	9706187	9706253
ENSE00003580266	9680725	9680800
ENSE00003583648	9615582	9615677
ENSE00003588514	9679951	9679987
ENSE00003632646	9748024	9748212
ENSE00003646468	9726641	9726720
ENSE00003656679	9706811	9706997
ENSE00003658322	9704663	9704757
ENSE00003841776	9555912	9556612

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 95.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.1537 / max 249.2237, expressed in 1809 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87309	21.8585	1809
87312	0.5880	133
87313	0.3232	102
87318	0.2218	51
87314	0.1074	45
87316	0.0307	12
87315	0.0135	3
87317	0.0107	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	95.93	gold quality
medial globus pallidus	UBERON:0002477	95.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.03	gold quality
corpus callosum	UBERON:0002336	94.75	gold quality
pons	UBERON:0000988	94.33	gold quality
globus pallidus	UBERON:0001875	94.05	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.04	gold quality
cortical plate	UBERON:0005343	94.02	gold quality
superior vestibular nucleus	UBERON:0007227	93.46	gold quality
inferior vagus X ganglion	UBERON:0005363	93.23	gold quality
medulla oblongata	UBERON:0001896	93.05	gold quality
corpus epididymis	UBERON:0004359	93.01	gold quality
tibia	UBERON:0000979	92.96	gold quality
subthalamic nucleus	UBERON:0001906	92.94	gold quality
inferior olivary complex	UBERON:0002127	92.82	gold quality
cerebellar vermis	UBERON:0004720	92.49	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.33	gold quality
dorsal plus ventral thalamus	UBERON:0001897	92.13	gold quality
substantia nigra pars compacta	UBERON:0001965	91.80	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.57	gold quality
sperm	CL:0000019	91.49	gold quality
postcentral gyrus	UBERON:0002581	91.46	gold quality
caput epididymis	UBERON:0004358	91.39	gold quality
ganglionic eminence	UBERON:0004023	91.36	gold quality
parietal lobe	UBERON:0001872	91.11	gold quality
entorhinal cortex	UBERON:0002728	91.11	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.80	gold quality
primary visual cortex	UBERON:0002436	90.76	gold quality
choroid plexus epithelium	UBERON:0003911	90.69	gold quality
endothelial cell	CL:0000115	90.68	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-4850	no	225.38
E-ANND-3	no	2.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

260 targeting TNKS, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548AW	99.99	72.57	3559

Literature-anchored findings (GeneRIF, showing 40)

• The telomeric poly(ADP-ribose) polymerase, tankyrase 1, contains multiple binding sites for telomeric repeat binding factor 1 (TRF1) and a novel acceptor, 182-kDa tankyrase-binding protein (TAB182). (PMID:11854288)
• Identification of a binding motif shared by IRAP TAB182, and human TRF1 but not mouse TRF1 (PMID:12080061)
• Results describe the expression and enzymatic characterization of full-length tankyrase 1 and a fragment, termed T-PARP, spanning the poly(ADP-ribose) polymerase domain. (PMID:12381316)
• Tankyrase 1 interacts with Mcl-1 proteins and inhibits their regulation of apoptosis (PMID:12475993)
• co-immunoprecipitation of endogenous proteins in 293T cells confirms physiological relevance of TNKS as interaction partner of FBP17 (PMID:14596906)
• Results provide evidence that specific ankyrin repeat cluster-TRF1 interactions play roles in the essential catalytic function of tankyrase 1. (PMID:14966275)
• telomeres may require a unique tankyrase 1-dependent mechanism for sister chromatid resolution before anaphase (PMID:15064417)
• TIN2 protected TRF1 from poly(ADP-ribosyl)ation by tankyrase 1 without affecting tankyrase 1 automodification. (PMID:15133513)
• TNKS1 bound to Epstein-Barr virus origin of plasmid replication in coimmunoprecipitation experiments with transfected cell lysates. (PMID:15795250)
• The role of TNKS in the poly(ADP-ribosyl)ation of the mitotic spindle apparatus is reported. (PMID:16076287)
• tankyrase-1 appears to protect cells by preventing genotoxins from activating PARP 1-mediated reactions such as PARP 1 automodification and NAD(+) consumption (PMID:16132700)
• Cell-cell contact makes tankyrase associate with the lateral membrane. PARsylating activity causes translocation to cytosol, ubiquitination & proteasomal degradation. Recruitment to this site suggests a role in polarized protein targeting in epithelium. (PMID:16884355)
• tankyrase1 is a poly(ADP-ribose) polymerase with roles in telomere length control by the TRF1 component of the shelterin complex (PMID:17561506)
• TNKL and TNKS are aberrantly expressed in colon tumors and contain multiple epitopes that induce humoral and cellular immune responses in cancer patients (PMID:18026951)
• The structure of the catalytic poly(ADP-ribose) polymerase (PARP) domain of human tankyrase 1 is reported. (PMID:18436240)
• This paper suggests a novel candidate gene for Cornelia de Lange syndrome - tankyrase 1. (PMID:18470924)
• Data suggest that pADPr provides a dynamic cross-linking function at spindle poles by extending from covalent modification sites on PARP-5a and NuMA and binding noncovalently to NuMA and that this function helps promote assembly of exactly two poles. (PMID:19759176)
• Data show that 4-oxo-4-HPR inhibited tubulin polymerization and modulated gene expression of spindle aberration associated genes Kif 1C, Kif 2A, Eg5, Tara, tankyrase-1, centractin, and TOGp. (PMID:19996280)
• These observations suggest that tankyrase-1 assembly to large protein complexes masks its telomeric function. (PMID:20696165)
• inhibition of tankyrase 1 could shorten telomere length and play a synergistic role with telomerase inhibitors in telomere length shortening in the SGC-7901 gastric cancer cell line (PMID:20811689)
• Tankyrase 1-PARP regulates stabilization of the NHEJ protein DNA-PKcs, revealing a new aspect of DNA-PKcs regulation that impacts both telomere and DNA repair functions. (PMID:21037379)
• High tankyrase 1 and telomerase expression is associated with gastric cancer. (PMID:21455637)
• RNF146 RING-type ubiquitin E3 ligase as a positive regulator of Wnt signaling that operates with tankyrase to maintain low steady-state levels of Axin proteins (PMID:21799911)
• Phosphorylation of TNKS1 by Plk1 may help regulate mitotic spindle assembly and promote telomeric chromatin maintenance. (PMID:21818122)
• In the early phase of infection, HSV ICP0 interacts with tankyrase 1 and mediates its nuclear translocation. (PMID:22013039)
• TNKS1 may have a key role in astrocytomas through its involvement in the Wnt/beta-catenin signaling pathway. (PMID:22154485)
• crystal structure of the catalytic domain of TNKS1 in complex with IWR2, which reveals a novel binding site for tankyrase inhibitors (PMID:22438990)
• GMD inhibits tankyrase 1 poly(ADP-ribose) polymerase activity in vitro, dependent on the GMD tankyrase 1 binding motif. In vivo, depletion of GMD led to degradation of tankyrase 1, dependent on the catalytic PARP activity of tankyrase 1. (PMID:22645305)
• CPAP degradation and function is controlled by the poly(ADP-ribose) polymerase tankyrase 1. (PMID:22699936)
• The data suggest that PARsylation of Miki by tankyrase-1 is a key initial event promoting prometaphase. (PMID:22864114)
• tankyrase-1 activity is required for initiation of T-oligo induced damage responses including p53 phosphorylation and reduction of cellular proliferation. (PMID:23800953)
• The present study suggests that combination of the inhibitors of telomerase and tankyrase can be used as a strategy for the treatment of lung cancer in humans. (PMID:23933993)
• Data indicate a basis for development of flavones as tankyrase inhibitors and suggest the development of other structurally related inhibitors. (PMID:24116873)
• Studies show a significant interaction of IWR1 with acidic and polar residues (Asp and Tyr) in the hydrophobic region at the induced pocket of TNKS1/TNKS2. These two residues are the key for the mechanism of inhibition of TNKS proteins. (PMID:24291818)
• We demonstrate for the first time that tankyrase inhibition triggers reduced cell growth and differentiation of OS cells (PMID:24403055)
• This limits the therapeutic value of TNKSi in colorectal carcinomas. (PMID:24419084)
• A novel function of TNKS in the relief of a feedback loop induced by MEK inhibition on FGFR2 signaling pathway. (PMID:24747911)
• tankyrase-mediated PARsylation is promoted by nutritional energy stimulated NAD+ in insulinoma cells (PMID:25876076)
• Copy number deletion on TNKS was associated with a 1.37-fold decreased risk for osteoarthritis. (PMID:25880085)
• Data indicate that tankyrase (Tnks) inhibitors impact telomere length maintenance independently of their affects on Wnt/beta-catenin signaling. (PMID:25939383)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tnksb	ENSDARG00000062897
danio_rerio	tnksa	ENSDARG00000077650
mus_musculus	Tnks	ENSMUSG00000031529
rattus_norvegicus	Tnks	ENSRNOG00000011625
drosophila_melanogaster	Tnks	FBGN0027508
caenorhabditis_elegans	tnsl-1	WBGENE00010498

Paralogs (2): TNKS2 (ENSG00000107854), ANKRD45 (ENSG00000183831)

Protein

Protein identifiers

Poly [ADP-ribose] polymerase tankyrase-1 — O95271 (reviewed: O95271)

Alternative names: ADP-ribosyltransferase diphtheria toxin-like 5, Poly [ADP-ribose] polymerase 5A, Protein poly-ADP-ribosyltransferase tankyrase-1, TNKS-1, TRF1-interacting ankyrin-related ADP-ribose polymerase, Tankyrase I, Tankyrase-1

All UniProt accessions (7): O95271, A0A0C4DGE3, A0AA34QVM1, E5RHD2, E7EQ52, E7EWY6, H0YAW5

UniProt curated annotations — full annotation on UniProt →

Function. Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1. Stimulates 26S proteasome activity.

Subunit / interactions. Oligomerizes and associates with TNKS2. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles. Binds to the N-terminus of telomeric TERF1 via the ANK repeats. Found in a complex with POT1; TERF1 and TINF2. Interacts with AXIN1. Interacts with AXIN2. Interacts with BLZF1 and CASC3. Interacts with NUMA1.

Subcellular location. Cytoplasm. Golgi apparatus membrane. Cytoskeleton. Microtubule organizing center. Centrosome. Nucleus. Nuclear pore complex. Chromosome. Telomere. Spindle pole.

Tissue specificity. Ubiquitous; highest levels in testis.

Post-translational modifications. Phosphorylated on serine residues by MAPK kinases upon insulin stimulation. Phosphorylated during mitosis. Ubiquitinated by RNF146 when auto-poly-ADP-ribosylated, leading to its degradation. Deubiquitinated by USP25; leading to stabilization. ADP-ribosylated (-auto). Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination.

Activity regulation. Specifically inhibited by XAV939, a small molecule, leading to inhibit the Wnt signaling pathway by stabilizing AXIN1 and AXIN2. Inhibited by talazoparib. Not inhibited by olaparib, niraparib and veliparib.

Similarity. Belongs to the ARTD/PARP family.

Isoforms (2)

UniProt ID	Names	Canonical?
O95271-1	1	yes
O95271-2	2

RefSeq proteins (1): NP_003738* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR012317	Poly(ADP-ribose)pol_cat_dom	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF00023, PF00644, PF07647, PF12796

Enzyme classification (BRENDA):

• EC 2.4.2.30 — NAD+ ADP-ribosyltransferase (BRENDA: 32 organisms, 193 substrates, 306 inhibitors, 42 Km, 24 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.002–0.251	25
(ADP-D-RIBOSYL)N-ACTIN	0.011–0.037	7
(ADP-D-RIBOSYL)N-SOYBEAN-TRYPSIN-INHIBITOR	0.03–0.429	6
(ADP-D-RIBOSYL)N-RHOA PROTEIN	0.017	1
N6-ETHENO-NAD+	0.0225	1

Catalyzed reactions (Rhea), 2 shown:

• L-aspartyl-[protein] + NAD(+) = 4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + nicotinamide (RHEA:54424)
• L-glutamyl-[protein] + NAD(+) = 5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + nicotinamide (RHEA:58224)

UniProt features (120 total): helix 53, repeat 21, strand 13, turn 12, compositionally biased region 4, binding site 4, sequence conflict 4, domain 2, region of interest 2, splice variant 2, mutagenesis site 2, chain 1

Structure

Experimental structures (PDB)

42 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6QXU	X-RAY DIFFRACTION	1.2
7KKP	X-RAY DIFFRACTION	1.4
7OCV	X-RAY DIFFRACTION	1.43
7KKN	X-RAY DIFFRACTION	1.48
4TOR	X-RAY DIFFRACTION	1.5
5GP7	X-RAY DIFFRACTION	1.5
7KKO	X-RAY DIFFRACTION	1.56
7KKM	X-RAY DIFFRACTION	1.58
7KKQ	X-RAY DIFFRACTION	1.59
8X5J	X-RAY DIFFRACTION	1.7
4MSG	X-RAY DIFFRACTION	1.8
4TOS	X-RAY DIFFRACTION	1.8
4DVI	X-RAY DIFFRACTION	1.9
4N3R	X-RAY DIFFRACTION	1.9
3UDD	X-RAY DIFFRACTION	1.95
4W6E	X-RAY DIFFRACTION	1.95
3UH2	X-RAY DIFFRACTION	2
3UH4	X-RAY DIFFRACTION	2
4MT9	X-RAY DIFFRACTION	2
4N4V	X-RAY DIFFRACTION	2
4LI6	X-RAY DIFFRACTION	2.05
6URQ	X-RAY DIFFRACTION	2.05
4LI7	X-RAY DIFFRACTION	2.2
5ECE	X-RAY DIFFRACTION	2.2
5EBT	X-RAY DIFFRACTION	2.24
4KRS	X-RAY DIFFRACTION	2.29
2RF5	X-RAY DIFFRACTION	2.3
4K4E	X-RAY DIFFRACTION	2.3
4MSK	X-RAY DIFFRACTION	2.3
4OA7	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95271-F1	76.44	0.50

Functional residue map

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

Ligand- & substrate-binding residues (4): 1234; 1237; 1242; 1245

Mutagenesis-validated functional residues (2):

Position	Phenotype
1184	loss of activity; when associated with a-1291.
1291	loss of activity; when associated with a-1184.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-4641257	Degradation of AXIN
R-HSA-5545619	XAV939 stabilizes AXIN
R-HSA-5689880	Ub-specific processing proteases
R-HSA-8948751	Regulation of PTEN stability and activity

MSigDB gene sets: 0 (showing top):

GO Biological Process (20): protein polyubiquitination (GO:0000209), mitotic spindle organization (GO:0007052), protein transport (GO:0015031), Wnt signaling pathway (GO:0016055), peptidyl-serine phosphorylation (GO:0018105), peptidyl-threonine phosphorylation (GO:0018107), regulation of telomere maintenance via telomerase (GO:0032210), positive regulation of telomere maintenance via telomerase (GO:0032212), positive regulation of transcription by RNA polymerase II (GO:0045944), mRNA transport (GO:0051028), spindle assembly (GO:0051225), cell division (GO:0051301), protein localization to chromosome, telomeric region (GO:0070198), protein poly-ADP-ribosylation (GO:0070212), protein auto-ADP-ribosylation (GO:0070213), positive regulation of canonical Wnt signaling pathway (GO:0090263), positive regulation of telomere capping (GO:1904355), negative regulation of telomere maintenance via telomere lengthening (GO:1904357), positive regulation of telomere maintenance via telomere lengthening (GO:1904358), negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric (GO:1904908)

GO Molecular Function (12): NAD+ poly-ADP-ribosyltransferase activity (GO:0003950), zinc ion binding (GO:0008270), telomerase inhibitor activity (GO:0010521), nucleotidyltransferase activity (GO:0016779), histone binding (GO:0042393), NAD+-protein-aspartate ADP-ribosyltransferase activity (GO:0140806), NAD+-protein-glutamate ADP-ribosyltransferase activity (GO:0140807), NAD+-protein mono-ADP-ribosyltransferase activity (GO:1990404), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), metal ion binding (GO:0046872)

GO Cellular Component (18): Golgi membrane (GO:0000139), pericentriolar material (GO:0000242), chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), nuclear body (GO:0016604), nuclear membrane (GO:0031965), mitotic spindle pole (GO:0097431), spindle pole (GO:0000922), nuclear envelope (GO:0005635), chromosome (GO:0005694), centrosome (GO:0005813), cytoskeleton (GO:0005856), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by WNT	1
TCF dependent signaling in response to WNT	1
Signaling by WNT in cancer	1
Deubiquitination	1
PTEN Regulation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
regulation of telomere maintenance via telomere lengthening	3
intracellular membraneless organelle	3
spindle organization	2
protein phosphorylation	2
telomere maintenance via telomerase	2
post-translational protein modification	2
positive regulation of telomere maintenance	2
telomere maintenance via telomere lengthening	2
pentosyltransferase activity	2
NAD+-protein mono-ADP-ribosyltransferase activity	2
intracellular membrane-bounded organelle	2
nuclear envelope	2
cytoplasm	2
endomembrane system	2
nucleus	2
protein ubiquitination	1
mitotic cell cycle	1
microtubule cytoskeleton organization involved in mitosis	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
cell surface receptor signaling pathway	1
peptidyl-serine modification	1
peptidyl-threonine modification	1
regulation of DNA biosynthetic process	1
regulation of telomere maintenance via telomerase	1
positive regulation of telomere maintenance via telomere lengthening	1
positive regulation of DNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
RNA transport	1
chromosome segregation	1
membraneless organelle assembly	1
cellular process	1
protein localization to chromosome	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1

Protein interactions and networks

STRING

2419 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNKS	TERF1	P54274	999
TNKS	AXIN1	O15169	983
TNKS	CNOT12	Q9C0C2	983
TNKS	TINF2	Q9BSI4	956
TNKS	RNF146	Q9NTX7	907
TNKS	NUMA1	Q14980	884
TNKS	TERF2	Q15554	859
TNKS	POT1	Q9NUX5	828
TNKS	PARP1	P09874	821
TNKS	AXIN2	Q9Y2T1	794
TNKS	MACROH2A1	O75367	781
TNKS	MCL1	Q07820	777
TNKS	SH3BP2	P78314	774
TNKS	KIF3A	Q9Y496	770
TNKS	CTNNB1	P35222	769

IntAct

184 interactions, top by confidence:

A	B	Type	Score
TNKS	TERF1	psi-mi:“MI:0915”(physical association)	0.850
TERF1	TNKS	psi-mi:“MI:0914”(association)	0.850
TERF1	TNKS	psi-mi:“MI:0915”(physical association)	0.850
TNKS	TERF1	psi-mi:“MI:0403”(colocalization)	0.850
HIF1AN	TNKS	psi-mi:“MI:0210”(hydroxylation reaction)	0.830
TNKS	HIF1AN	psi-mi:“MI:0210”(hydroxylation reaction)	0.830
RNF146	TNKS	psi-mi:“MI:0407”(direct interaction)	0.790
RNF146	TNKS	psi-mi:“MI:0915”(physical association)	0.790
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
INAVA	CYTH3	psi-mi:“MI:0914”(association)	0.640
HIF1AN	GMDS	psi-mi:“MI:0914”(association)	0.640
BLZF1	TNKS	psi-mi:“MI:0914”(association)	0.640
BABAM1	TNKS	psi-mi:“MI:0914”(association)	0.640
SLC35A5	TNKS	psi-mi:“MI:0914”(association)	0.640
MAPK8IP3	RCCD1	psi-mi:“MI:0914”(association)	0.640
MCL1	PRKAB2	psi-mi:“MI:0914”(association)	0.640

BioGRID (225): TNKS (Reconstituted Complex), TNKS (Affinity Capture-MS), TNKS (Affinity Capture-MS), TNKS (Affinity Capture-MS), TNKS (Affinity Capture-MS), TNKS (Affinity Capture-MS), TNKS (Affinity Capture-MS), TNKS (Affinity Capture-MS), TNKS (Affinity Capture-MS), TNKS (Affinity Capture-MS), TNKS (Affinity Capture-Western), AXIN1 (Affinity Capture-Western), PTEN (Affinity Capture-Western), PTEN (Biochemical Activity), TNKS (Biochemical Activity)

ESM2 similar proteins: A0A0C3RR82, A4IFC9, D0ZPH9, D0ZVG2, E5AV36, E5AW43, E5AW45, O70511, O95271, P08685, P0CE12, P17778, P23325, P23799, P25071, P46080, P50938, P73892, P77147, Q1RHU9, Q1RI31, Q3UES3, Q4UKZ9, Q4UNE4, Q56830, Q5REA0, Q5SF93, Q5SF95, Q5U2W6, Q5UP11, Q5UPA2, Q5UPD5, Q5UPE2, Q5UPG5, Q5UQF1, Q5UQJ2, Q5UQZ7, Q60278, Q60279, Q60585

Diamond homologs: B0G124, O95271, Q337A0, Q3V096, Q4JHE0, Q55FM5, Q6PFX9, Q86WC6, Q876A6, Q8N9B4, Q9D119, Q9J512, Q09701, Q24009, Q3UES3, Q63746, Q9H2K2, Q9VBP3, Q9Z1E3, V6CLA2, Q10728, Q1RJ94, Q5H9F3, Q5TYM7, Q5XIU1, Q6P1S6, Q969K4, Q99LJ2, Q9DBR7, Q9P2R3, Q9XZC0, B4E2M5, C7B178, L7XCU0, O43150, O75762, P25631, P28492, P77736, Q01317

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
TNKS	“down-regulates quantity by destabilization”	AXIN1	ubiquitination
TNKS	“down-regulates quantity by destabilization”	AXIN2	ubiquitination
XAV939	down-regulates	TNKS	“chemical inhibition”
RNF146	“down-regulates quantity”	TNKS	ubiquitination
TNKS	“down-regulates quantity by destabilization”	GSK3B/Axin/APC
TNKS	“up-regulates activity”	RNF146
TNKS	“down-regulates quantity by destabilization”	AXIN1	ADP-ribosylation
TNKS	“down-regulates quantity by destabilization”	AXIN2	ADP-ribosylation
TNKS	“down-regulates quantity by destabilization”	CASC3	ADP-ribosylation
TNKS	“down-regulates quantity by destabilization”	BLZF1	ADP-ribosylation
TNKS	“down-regulates quantity by destabilization”	PSMF1	ADP-ribosylation
PLK1	“up-regulates quantity by stabilization”	TNKS	phosphorylation
TNKS	“up-regulates quantity by stabilization”	TARDBP	binding
XAV939	“down-regulates activity”	TNKS	“chemical inhibition”
TNKS	“down-regulates activity”	TERF1	ADP-ribosylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	172
Likely benign	4
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

4851 predictions. Top by Δscore:

Variant	Effect	Δscore
8:9556584:G:GT	donor_gain	1.0000
8:9556608:TGCAG:T	donor_loss	1.0000
8:9556609:GCAGG:G	donor_loss	1.0000
8:9556610:CAG:C	donor_loss	1.0000
8:9556611:AG:A	donor_loss	1.0000
8:9556612:GGTC:G	donor_loss	1.0000
8:9556613:G:GA	donor_loss	1.0000
8:9580154:TTTA:T	acceptor_loss	1.0000
8:9580155:TTA:T	acceptor_loss	1.0000
8:9580157:A:AG	acceptor_gain	1.0000
8:9580157:AG:A	acceptor_gain	1.0000
8:9580158:G:GC	acceptor_gain	1.0000
8:9580158:GG:G	acceptor_gain	1.0000
8:9580158:GGT:G	acceptor_gain	1.0000
8:9580158:GGTT:G	acceptor_gain	1.0000
8:9580158:GGTTT:G	acceptor_gain	1.0000
8:9580364:G:T	donor_gain	1.0000
8:9580379:CATTG:C	donor_gain	1.0000
8:9580380:ATTG:A	donor_gain	1.0000
8:9580381:TTG:T	donor_gain	1.0000
8:9580382:TG:T	donor_gain	1.0000
8:9580383:GG:G	donor_gain	1.0000
8:9580384:G:GG	donor_gain	1.0000
8:9580384:GTAA:G	donor_loss	1.0000
8:9580385:TAAG:T	donor_loss	1.0000
8:9615575:T:TA	acceptor_gain	1.0000
8:9615578:A:AG	acceptor_gain	1.0000
8:9615578:ACAGT:A	acceptor_gain	1.0000
8:9615579:C:G	acceptor_gain	1.0000
8:9615579:CAGTG:C	acceptor_loss	1.0000

AlphaMissense

8631 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:9556507:T:C	C190R	1.000
8:9556508:G:A	C190Y	1.000
8:9556509:T:G	C190W	1.000
8:9556516:G:A	G193R	1.000
8:9556516:G:C	G193R	1.000
8:9556516:G:T	G193W	1.000
8:9556517:G:A	G193E	1.000
8:9556517:G:T	G193V	1.000
8:9556598:T:A	L220Q	1.000
8:9556598:T:C	L220P	1.000
8:9556600:C:G	H221D	1.000
8:9556601:A:G	H221R	1.000
8:9556603:T:C	F222L	1.000
8:9556604:T:C	F222S	1.000
8:9556605:C:A	F222L	1.000
8:9556605:C:G	F222L	1.000
8:9556607:C:A	A223D	1.000
8:9556610:C:A	A224E	1.000
8:9556612:G:C	G225R	1.000
8:9580159:G:A	G225D	1.000
8:9580161:T:C	F226L	1.000
8:9580163:T:A	F226L	1.000
8:9580163:T:G	F226L	1.000
8:9580164:G:A	G227R	1.000
8:9580164:G:C	G227R	1.000
8:9580165:G:A	G227E	1.000
8:9580165:G:T	G227V	1.000
8:9580168:G:C	R228T	1.000
8:9580168:G:T	R228M	1.000
8:9580169:G:C	R228S	1.000

dbSNP variants (sampled 300 via entrez): RS1000027447 (8:9762886 C>A,G), RS1000028743 (8:9631898 A>C), RS1000044423 (8:9703777 A>G), RS1000080750 (8:9632111 G>A,T), RS1000104906 (8:9697828 C>A,T), RS1000105436 (8:9699191 G>A,T), RS1000107308 (8:9665448 C>G), RS1000108133 (8:9731368 G>A,C), RS1000113789 (8:9616180 A>T), RS1000115976 (8:9655868 C>A), RS1000122577 (8:9596409 A>C,G), RS1000130940 (8:9709005 T>C), RS1000139852 (8:9764354 T>C), RS1000140099 (8:9607172 G>A,C), RS1000140675 (8:9731530 C>T)

Disease associations

OMIM: gene MIM:603303 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

81 associations (top):

Study	Trait	p-value
GCST000663_5	Obesity (early onset extreme)	2.000000e-08
GCST001639_23	Metabolite levels	2.000000e-09
GCST002432_5	Response to inhaled corticosteroid treatment in asthma (change in FEV1)	4.000000e-06
GCST002481_5	Acne (severe)	9.000000e-07
GCST003048_59	Schizophrenia	4.000000e-08
GCST003654_14	Bone mineral density (Ward’s triangle area)	2.000000e-06
GCST003998_15	Joint mobility (Beighton score)	1.000000e-07
GCST003999_4	Nose size	6.000000e-11
GCST004863_17	Mosquito bite size	3.000000e-07
GCST005752_171	Systemic lupus erythematosus	1.000000e-07
GCST006166_24	Diastolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-13
GCST006166_66	Diastolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-13
GCST006168_49	Pulse pressure x alcohol consumption interaction (2df test)	1.000000e-08
GCST006190_34	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-09
GCST006190_45	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-06
GCST006190_70	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-06
GCST006190_78	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-09
GCST006190_87	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-09
GCST006190_9	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-06
GCST006192_21	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-13
GCST006192_53	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-14
GCST006192_7	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-13
GCST006192_80	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-07
GCST006193_18	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-08
GCST006193_28	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-08
GCST006193_42	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	7.000000e-07
GCST006193_58	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-08
GCST006193_68	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	5.000000e-08
GCST006193_80	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	8.000000e-10
GCST006195_27	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	9.000000e-12

EFO canonical traits (23, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0005921	FEV change measurement
EFO:0007785	femoral neck bone mineral density
EFO:0007905	joint hypermobility measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004329	alcohol drinking
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0009592	social interaction measurement
EFO:0008579	risk-taking behaviour
EFO:0008111	diet measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:1001904	oral mucositis
EFO:0004346	neuroimaging measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0009101	age at first birth measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3038515 (PROTEIN FAMILY), CHEMBL6164 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 152,305 (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
CHEMBL1094636	NIRAPARIB	4	6,433
CHEMBL1173055	RUCAPARIB	4	7,009
CHEMBL3137320	TALAZOPARIB	4	5,534
CHEMBL521686	OLAPARIB	4	13,038
CHEMBL4112930	PAMIPARIB	3	2,114
CHEMBL506871	VELIPARIB	3	5,421
CHEMBL3644587	2X-121	2	248
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL275638	FLAVONE	2	88,985

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Poly ADP-ribosylating PARPs

Most potent curated ligand interactions (8 total), top 8:

Ligand	Action	Affinity	Parameter
compound 21 [PMID: 34141085]	Inhibition	8.4	pIC50
basroparib	Inhibition	8.24	pIC50
AZ6102	Inhibition	8.22	pIC50
compound 5 [Tomassi et al., 2020]	Inhibition	8.21	pIC50
AZ1366	Inhibition	8.15	pIC50
RK-287107	Inhibition	7.84	pIC50
NVP‐TNKS656	Inhibition	7.81	pIC50
MC2050	Inhibition	6.66	pIC50

Binding affinities (BindingDB)

483 measured of 543 human assays (545 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[4-(5-cyano-2-oxo-3H-benzimidazol-1-yl)cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.045 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)cyclohexyl]-2-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]acetamide	IC50	0.0597 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(3-methoxyphenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.0647 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.0724 nM	US-9505749: Quinazolinone compounds and derivatives thereof
3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]-N-[3-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclobutyl]propanamide	IC50	0.0891 nM	US-9505749: Quinazolinone compounds and derivatives thereof
4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)-N-[4-(5-phenyl-1,3-oxazol-2-yl)cyclohexyl]butanamide	IC50	0.0979 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.107 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(6-chloro-2-oxo-3H-benzimidazol-1-yl)cyclohexyl]-2-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]acetamide	IC50	0.118 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.127 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(5-cyano-2-oxo-3H-benzimidazol-1-yl)cyclohexyl]-2-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]acetamide	IC50	0.129 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(4-chlorophenoxy)cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.145 nM	US-9505749: Quinazolinone compounds and derivatives thereof
3-[(6-fluoro-4-oxo-6H-quinazolin-2-yl)sulfanyl]-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclohexyl]propanamide	IC50	0.148 nM	US-9505749: Quinazolinone compounds and derivatives thereof
3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]-N-(4-pyridin-4-yloxycyclohexyl)propanamide	IC50	0.153 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(3-chloro-4-fluorophenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.153 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	0.161 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(4-cyanophenoxy)cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.167 nM	US-9505749: Quinazolinone compounds and derivatives thereof
3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]-N-(4-pyridin-2-yloxycyclohexyl)propanamide	IC50	0.176 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(3-chloro-4-cyanophenoxy)cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.176 nM	US-9505749: Quinazolinone compounds and derivatives thereof
4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)-N-[4-(2-oxo-3H-benzimidazol-1-yl)cyclohexyl]butanamide	IC50	0.186 nM	US-9505749: Quinazolinone compounds and derivatives thereof
3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclohexyl]propanamide	IC50	0.187 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(3-fluorophenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.194 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(3-cyanophenoxy)cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.206 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(3-chlorophenoxy)cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.224 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(4-fluorophenoxy)cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.237 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.269 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(3-chloro-4-fluorophenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	0.277 nM	US-9505749: Quinazolinone compounds and derivatives thereof
3-[(4-oxo-4aH-quinazolin-2-yl)sulfanyl]-N-[4-(5-pyridin-4-yl-1,3,4-oxadiazol-2-yl)cyclohexyl]propanamide	IC50	0.287 nM	US-9505749: Quinazolinone compounds and derivatives thereof
(4S)-5,5-dimethyl-3-[4-(2-oxo-1-pyrimidin-2-yl-3H-imidazo[4,5-b]pyridin-6-yl)cyclohexyl]-4-phenyl-1,3-oxazolidin-2-one	IC50	0.316 nM	US-9340549: Oxazolidinone compounds and derivatives thereof
N-[4-(4-chloro-3-cyanophenoxy)cyclohexyl]-3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]propanamide	IC50	0.323 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	0.367 nM	US-9505749: Quinazolinone compounds and derivatives thereof
1-[4-[(4S,5R)-5-methyl-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]cyclohexyl]-2-oxo-3H-benzimidazole-5-carbonitrile	IC50	0.375 nM	US-9340549: Oxazolidinone compounds and derivatives thereof
3-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]-N-[3-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclobutyl]propanamide	IC50	0.405 nM	US-9505749: Quinazolinone compounds and derivatives thereof
4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)-N-[4-(5-pyridin-4-yl-1,3,4-oxadiazol-2-yl)cyclohexyl]butanamide	IC50	0.453 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(3-fluorophenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	0.469 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(3-methoxyphenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	0.495 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(5-chloro-2-oxo-3H-benzimidazol-1-yl)cyclohexyl]-3-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)propanamide	IC50	0.524 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	0.531 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	0.549 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	0.567 nM	US-9505749: Quinazolinone compounds and derivatives thereof
4-({3-[(4-cyclopropanecarbonylpiperazin-1-yl)carbonyl]-4-fluorophenyl}methyl)-1,2-dihydrophthalazin-1-one	IC50	0.9 nM	US-9255106: Substituted [1,2,4]triazolo[4,3-a]pyrazines as PARP-1 inhibitors
(4S)-5,5-dimethyl-4-phenyl-3-[4-(1-pyrimidin-2-ylpyrrolo[3,2-b]pyridin-6-yl)cyclohexyl]-1,3-oxazolidin-2-one	IC50	1.01 nM	US-9340549: Oxazolidinone compounds and derivatives thereof
N-[4-(6-chloro-2-oxo-3H-benzimidazol-1-yl)cyclohexyl]-3-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)propanamide	IC50	1.01 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(3-chloro-4-cyanophenoxy)cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	1.05 nM	US-9505749: Quinazolinone compounds and derivatives thereof
4-[(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)sulfanyl]-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclohexyl]butanamide	IC50	1.05 nM	US-9505749: Quinazolinone compounds and derivatives thereof
1-[4-[(4S)-5,5-dimethyl-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]cyclohexyl]-4-fluoro-2-oxo-3H-benzimidazole-5-carbonitrile	IC50	1.09 nM	US-9340549: Oxazolidinone compounds and derivatives thereof
1-[4-[(4S)-5,5-dimethyl-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]cyclohexyl]-2-oxo-3H-benzimidazole-5-carbonitrile	IC50	1.12 nM	US-9340549: Oxazolidinone compounds and derivatives thereof
3-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)-N-[4-(2-oxo-3H-benzimidazol-1-yl)cyclohexyl]propanamide	IC50	1.44 nM	US-9505749: Quinazolinone compounds and derivatives thereof
(4S)-3-[4-(6-amino-5-pyrimidin-2-yl-3-pyridinyl)cyclohexyl]-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one	IC50	1.47 nM	US-9340549: Oxazolidinone compounds and derivatives thereof
(4S)-3-[4-(6-bromo-2-oxo-1H-imidazo[4,5-b]pyridin-3-yl)cyclohexyl]-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one	IC50	1.48 nM	US-9340549: Oxazolidinone compounds and derivatives thereof
4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclohexyl]butanamide	IC50	1.52 nM	US-9505749: Quinazolinone compounds and derivatives thereof

ChEMBL bioactivities

1586 potent at pChembl≥5 of 1624 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.35	IC50	0.045	nM	CHEMBL5989994
10.32	IC50	0.048	nM	CHEMBL4646640
10.22	IC50	0.0597	nM	CHEMBL6052143
10.19	IC50	0.0647	nM	CHEMBL5880126
10.14	IC50	0.0724	nM	CHEMBL6059393
10.05	IC50	0.0891	nM	CHEMBL5766123
10.01	IC50	0.0979	nM	CHEMBL5853920
10.01	IC50	0.0973	nM	CHEMBL3110100
10.00	IC50	0.1	nM	CHEMBL3110100
10.00	IC50	0.1	nM	CHEMBL3110122
10.00	IC50	0.1	nM	CHEMBL3110117
10.00	IC50	0.1	nM	CHEMBL4442053
10.00	IC50	0.1	nM	CHEMBL4572668
10.00	IC50	0.1	nM	CHEMBL4553990
10.00	IC50	0.1	nM	CHEMBL4539435
10.00	IC50	0.1	nM	CHEMBL4446044
9.97	IC50	0.107	nM	CHEMBL5818177
9.96	IC50	0.109	nM	CHEMBL3110117
9.93	IC50	0.118	nM	CHEMBL5857702
9.90	IC50	0.127	nM	CHEMBL6040620
9.89	IC50	0.129	nM	CHEMBL5912168
9.84	IC50	0.145	nM	CHEMBL3110122
9.83	IC50	0.148	nM	CHEMBL6052029
9.81	IC50	0.153	nM	CHEMBL3110101
9.81	IC50	0.153	nM	CHEMBL5837720
9.79	IC50	0.161	nM	CHEMBL6057191
9.78	IC50	0.167	nM	CHEMBL5814332
9.75	IC50	0.176	nM	CHEMBL3110102
9.75	IC50	0.176	nM	CHEMBL3110106
9.74	IC50	0.18	nM	CHEMBL3805896
9.73	IC50	0.186	nM	CHEMBL5910083
9.73	IC50	0.187	nM	CHEMBL3110119
9.71	IC50	0.194	nM	CHEMBL5964048
9.70	IC50	0.2	nM	CHEMBL3110106
9.70	IC50	0.2	nM	CHEMBL3110104
9.70	IC50	0.2	nM	CHEMBL3110103
9.70	IC50	0.2	nM	CHEMBL3110102
9.70	IC50	0.2	nM	CHEMBL3110101
9.70	IC50	0.2	nM	CHEMBL3110121
9.70	IC50	0.2	nM	CHEMBL3110119
9.70	IC50	0.2	nM	CHEMBL3806163
9.70	IC50	0.2	nM	CHEMBL4585076
9.70	IC50	0.2	nM	CHEMBL4470270
9.70	IC50	0.2	nM	CHEMBL4532667
9.70	IC50	0.2	nM	CHEMBL4470218
9.69	IC50	0.206	nM	CHEMBL3110104
9.66	EC50	0.22	nM	CHEMBL3806163
9.65	IC50	0.224	nM	CHEMBL3110103
9.64	IC50	0.23	nM	CHEMBL5979326
9.62	IC50	0.24	nM	CHEMBL3805393

PubChem BioAssay actives

968 with measured affinity, of 1288 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
N-[3-[4-(2-chlorophenyl)-5-pyrimidin-4-yl-1,2,4-triazol-3-yl]cyclobutyl]-1,5-naphthyridine-4-carboxamide	1658113: Inhibition of TNKS1/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by dual-glo luciferase reporter gene assay	ic50	<0.0001	uM
3-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclohexyl]propanamide	1065807: Inhibition of 6x-His-tagged TNKS1 (unknown origin) after 60 mins	ic50	0.0001	uM
N-[4-(4-cyanophenoxy)cyclohexyl]-3-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]propanamide	1065807: Inhibition of 6x-His-tagged TNKS1 (unknown origin) after 60 mins	ic50	0.0001	uM
N-[4-(4-chlorophenoxy)cyclohexyl]-3-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]propanamide	1065807: Inhibition of 6x-His-tagged TNKS1 (unknown origin) after 60 mins	ic50	0.0001	uM
4-fluoro-6-(2-methoxyethoxy)-1-methyl-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0001	uM
6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-4-fluoro-1-methyl-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0001	uM
4-fluoro-1-methyl-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-(1-methylpiperidin-4-yl)oxyspiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0001	uM
4,6-difluoro-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1-(methylsulfonylmethyl)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0001	uM
4-fluoro-1-methyl-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-morpholin-4-ylspiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0001	uM
3-[4-[4-(4-methoxybenzoyl)piperidin-1-yl]-4-oxobutyl]-6-methyl-2H-pyrrolo[1,2-a]pyrazin-1-one	1299816: Inhibition of GST-tagged TNKS1 (1023 to 1327 residues) (unknown origin) autoparsylation using biotinylated NAD incubated for 1 hr by ELISA	ic50	0.0002	uM
7-fluoro-3-[4-[4-(4-methoxybenzoyl)piperidin-1-yl]-4-oxobutyl]-2H-pyrrolo[1,2-a]pyrazin-1-one	1299816: Inhibition of GST-tagged TNKS1 (1023 to 1327 residues) (unknown origin) autoparsylation using biotinylated NAD incubated for 1 hr by ELISA	ic50	0.0002	uM
7-fluoro-3-[4-[4-(6-methoxypyridine-3-carbonyl)piperidin-1-yl]-4-oxobutyl]-2H-pyrrolo[1,2-a]pyrazin-1-one	1299816: Inhibition of GST-tagged TNKS1 (1023 to 1327 residues) (unknown origin) autoparsylation using biotinylated NAD incubated for 1 hr by ELISA	ic50	0.0002	uM
3-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]-N-(4-pyridin-4-yloxycyclohexyl)propanamide	1065807: Inhibition of 6x-His-tagged TNKS1 (unknown origin) after 60 mins	ic50	0.0002	uM
N-[4-(3-cyanophenoxy)cyclohexyl]-3-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]propanamide	1065807: Inhibition of 6x-His-tagged TNKS1 (unknown origin) after 60 mins	ic50	0.0002	uM
3-[(4-oxo-5,6,7,8-tetrahydro-3H-quinazolin-2-yl)sulfanyl]-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclohexyl]propanamide	1065807: Inhibition of 6x-His-tagged TNKS1 (unknown origin) after 60 mins	ic50	0.0002	uM
N-[4-(3-chlorophenoxy)cyclohexyl]-3-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]propanamide	1065807: Inhibition of 6x-His-tagged TNKS1 (unknown origin) after 60 mins	ic50	0.0002	uM
N-[4-(3-chloro-4-cyanophenoxy)cyclohexyl]-3-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]propanamide	1065807: Inhibition of 6x-His-tagged TNKS1 (unknown origin) after 60 mins	ic50	0.0002	uM
3-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]-N-(4-pyridin-2-yloxycyclohexyl)propanamide	1065807: Inhibition of 6x-His-tagged TNKS1 (unknown origin) after 60 mins	ic50	0.0002	uM
N-[4-(4-fluorophenoxy)cyclohexyl]-3-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]propanamide	1065807: Inhibition of 6x-His-tagged TNKS1 (unknown origin) after 60 mins	ic50	0.0002	uM
2-[4,6-difluoro-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-oxospiro[indole-3,4’-piperidine]-1-yl]acetonitrile	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0002	uM
4-fluoro-6-methoxy-1-methyl-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0002	uM
4,6-difluoro-1-(2-hydroxyethyl)-1’-(8-methyl-4-oxo-3H-quinazolin-2-yl)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0002	uM
4,6-difluoro-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1-(2,2,2-trifluoroethyl)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0002	uM
N-[4-(4-chloro-3-cyanophenoxy)cyclohexyl]-3-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]propanamide	1065807: Inhibition of 6x-His-tagged TNKS1 (unknown origin) after 60 mins	ic50	0.0003	uM
6-[2-(dimethylamino)ethoxy]-4-fluoro-1-methyl-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0003	uM
6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-4-fluoro-1-methyl-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0003	uM
4-fluoro-1-methyl-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-(2-morpholin-4-ylethoxy)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0003	uM
5-[1-[ethyl-(4-methoxyphenyl)carbamoyl]piperidine-4-carbonyl]-1-methylindole-2-carboxylic acid	1666286: Inhibition of human GST-tagged tankyrase 1 autophosphorylation by ELISA	ic50	0.0003	uM
4-[ethyl-[4-(1-methylindazole-6-carbonyl)piperidine-1-carbonyl]amino]benzoic acid	1666286: Inhibition of human GST-tagged tankyrase 1 autophosphorylation by ELISA	ic50	0.0003	uM
4,6-difluoro-1-(2-methoxyethyl)-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0003	uM
4,6-difluoro-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-1-(oxetan-3-ylmethyl)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0003	uM
2-[4-[4-(4-methoxy-3-methylbenzoyl)piperidin-1-yl]-4-oxobutyl]-7-methyl-3H-thieno[3,4-d]pyrimidin-4-one	1299816: Inhibition of GST-tagged TNKS1 (1023 to 1327 residues) (unknown origin) autoparsylation using biotinylated NAD incubated for 1 hr by ELISA	ic50	0.0004	uM
4-fluoro-1-methyl-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-(2-pyrrolidin-1-ylethoxy)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0004	uM
N-[3-[4-(2-fluorophenyl)-5-(5-methylsulfonyl-2-pyridinyl)-1,2,4-triazol-3-yl]cyclobutyl]-1,5-naphthyridine-4-carboxamide	1658113: Inhibition of TNKS1/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by dual-glo luciferase reporter gene assay	ic50	0.0004	uM
4-[ethyl-[4-(3-methylbenzimidazole-5-carbonyl)piperidine-1-carbonyl]amino]benzoic acid	1666286: Inhibition of human GST-tagged tankyrase 1 autophosphorylation by ELISA	ic50	0.0004	uM
6-[1-[ethyl-(4-methoxyphenyl)carbamoyl]piperidine-4-carbonyl]-1-methylindole-2-carboxylic acid	1666286: Inhibition of human GST-tagged tankyrase 1 autophosphorylation by ELISA	ic50	0.0004	uM
4-[ethyl-[4-(1-methylindazole-5-carbonyl)piperidine-1-carbonyl]amino]benzoic acid	1666286: Inhibition of human GST-tagged tankyrase 1 autophosphorylation by ELISA	ic50	0.0005	uM
6-[1-[ethyl-(4-methoxyphenyl)carbamoyl]piperidine-4-carbonyl]-1-methylindazole-3-carboxylic acid	1666286: Inhibition of human GST-tagged tankyrase 1 autophosphorylation by ELISA	ic50	0.0005	uM
N-[3-[5-[5-(difluoromethoxy)-2-pyridinyl]-4-(2-fluorophenyl)-1,2,4-triazol-3-yl]cyclobutyl]-1,5-naphthyridine-4-carboxamide	1658113: Inhibition of TNKS1/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by dual-glo luciferase reporter gene assay	ic50	0.0006	uM
N-[3-[4-(2-fluorophenyl)-5-(5-methylsulfonyl-2-pyridinyl)-1,2,4-triazol-3-yl]cyclobutyl]quinoline-8-carboxamide	1658113: Inhibition of TNKS1/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by dual-glo luciferase reporter gene assay	ic50	0.0006	uM
N-[3-[5-(5-ethoxy-2-pyridinyl)-4-(2-fluorophenyl)-1,2,4-triazol-3-yl]cyclobutyl]-1,5-naphthyridine-4-carboxamide	1658113: Inhibition of TNKS1/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by dual-glo luciferase reporter gene assay	ic50	0.0006	uM
3-[4-(2-hydroxypropan-2-yl)phenyl]-6-methyl-2H-pyrrolo[1,2-a]pyrazin-1-one	1866937: Inhibition of GST-tagged TNKS1 (1023 - 1327 residues) (unknown origin) by ELISA	ic50	0.0006	uM
1-(2,3-dihydroxypropyl)-4,6-difluoro-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0007	uM
4-fluoro-1-methyl-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-piperidin-1-ylspiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0007	uM
7-methyl-2-[4-oxo-4-[4-(1-propan-2-ylpyrazole-4-carbonyl)piperidin-1-yl]butyl]-3H-pyrrolo[2,3-d]pyrimidin-4-one	1299816: Inhibition of GST-tagged TNKS1 (1023 to 1327 residues) (unknown origin) autoparsylation using biotinylated NAD incubated for 1 hr by ELISA	ic50	0.0008	uM
6-fluoro-2-[4-(2-hydroxypropan-2-yl)phenyl]-8-methyl-3H-quinazolin-4-one	1525648: Inhibition of GST tagged-TEV cleavage site-fused human recombinant TNKS1 (1023 to 1327 residues) expressed in baculovirus infected sf9 cells assessed as reduction in auto-PARsylation incubated for 1 hr in presence of bio-NAD as co-substrate by ELISA	ic50	0.0008	uM
2-[4-(2-hydroxypropan-2-yl)phenyl]-7-methyl-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one	1925188: Inhibition of TNKS1 (unknown origin) using biotinylated NAD as substrate assessed as inhibition of autoPARsylation activity incubated for 1 hr by ELISA	ic50	0.0008	uM
4-fluoro-6-(2-hydroxyethoxy)-1-methyl-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)spiro[indole-3,4’-piperidine]-2-one	1548006: Inhibition of TNKS/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by TCF-luciferase reporter gene assay	ic50	0.0008	uM
7-fluoro-N-[3-[4-(2-fluorophenyl)-5-pyridin-2-yl-1,2,4-triazol-3-yl]cyclobutyl]-1,5-naphthyridine-4-carboxamide	1658113: Inhibition of TNKS1/TNKS2 (unknown origin) expressed in HEK293 cells assessed as reduction in Wnt-signaling measured after 24 hrs by dual-glo luciferase reporter gene assay	ic50	0.0008	uM
N-[(2S)-3-[3-(2,4-dioxoquinazolin-1-yl)propanoylamino]-1-(methylamino)-1-oxopropan-2-yl]quinoline-3-carboxamide	1980205: Inhibition of TNKS1 (unknown origin) using biotinylated NAD as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by BioTek synergy 2 microplate reader analysis	ic50	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	6
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects binding, decreases reaction, affects localization, increases metabolic processing	4
Ozone	affects cotreatment, increases expression, increases abundance, affects expression	3
arsenite	affects binding, decreases reaction, increases methylation	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
XAV939	affects binding, decreases reaction, decreases activity	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	increases abundance, increases expression, affects expression, affects cotreatment	2
dimethoxon	increases response to substance	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
bisphenol A	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Bortezomib	decreases expression, increases response to substance	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Curcumin	decreases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Etoposide	affects response to substance	1

ChEMBL screening assays

226 unique, capped per target: 223 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2317528	Binding	Inhibition of Tankyrase in human HEK293 cells assessed as inhibition of Wnt pathway by Wnt3a-induced STF assay	Discovery of a class of novel tankyrase inhibitors that bind to both the nicotinamide pocket and the induced pocket. — J Med Chem
CHEMBL5723131	Functional	Affinity Biochemical interaction: (automodification of tankyrases with D+ as substrate, the remainder of which is converted into a stable fluorescent condensation product) EUB0002225aCl TNKS1	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8XE	Ubigene HCT 116 TNKS KO	Cancer cell line	Male
CVCL_TT16	HAP1 TNKS (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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