TNKS2

Summary

TNKS2 (tankyrase 2, HGNC:15677) is a protein-coding gene on chromosome 10q23.32, encoding Poly [ADP-ribose] polymerase tankyrase-2 (Q9H2K2). Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking.

Enables NAD+ poly-ADP-ribosyltransferase activity; NAD+-protein mono-ADP-ribosyltransferase activity; and enzyme binding activity. Involved in several processes, including positive regulation of canonical Wnt signaling pathway; post-translational protein modification; and regulation of telomere maintenance. Located in nuclear envelope; pericentriolar material; and perinuclear region of cytoplasm.

Source: NCBI Gene 80351 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 120 total
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_025235

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15677
Approved symbol	TNKS2
Name	tankyrase 2
Location	10q23.32
Locus type	gene with protein product
Status	Approved
Aliases	TNKL, TANK2, PARP-5b, PARP-5c, PARP5B, PARP5C, pART6, ARTD6
Ensembl gene	ENSG00000107854
Ensembl biotype	protein_coding
OMIM	607128
Entrez	80351

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000371627, ENST00000710380

RefSeq mRNA: 1 — MANE Select: NM_025235 NM_025235

CCDS: CCDS7417

Canonical transcript exons

ENST00000371627 — 27 exons

Exon	Start	End
ENSE00000713476	91851216	91851336
ENSE00000713479	91849512	91849594
ENSE00000713482	91848383	91848635
ENSE00000713487	91845752	91845940
ENSE00000713490	91844919	91845028
ENSE00000713496	91841283	91841448
ENSE00000713499	91840561	91840706
ENSE00000713504	91833853	91834024
ENSE00000713506	91831103	91831181
ENSE00000713509	91830923	91831014
ENSE00000713514	91828285	91828406
ENSE00000713519	91827017	91827203
ENSE00000713523	91822296	91822362
ENSE00000713528	91819939	91820033
ENSE00000713535	91819270	91819306
ENSE00000713540	91817134	91817229
ENSE00000810658	91812983	91813207
ENSE00000810659	91836919	91836998
ENSE00000986546	91855029	91855126
ENSE00000986547	91855614	91855688
ENSE00000986548	91857425	91857530
ENSE00000986549	91859462	91859648
ENSE00000986550	91861999	91862155
ENSE00001455700	91862937	91865475
ENSE00001455758	91798426	91798889
ENSE00001707484	91842172	91842391
ENSE00001727782	91819482	91819557

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 96.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.2884 / max 594.9924, expressed in 1816 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106221	24.7318	1795
106220	4.5566	1614

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.99	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.39	gold quality
secondary oocyte	CL:0000655	96.25	gold quality
biceps brachii	UBERON:0001507	96.13	gold quality
triceps brachii	UBERON:0001509	95.40	gold quality
choroid plexus epithelium	UBERON:0003911	95.37	gold quality
superior surface of tongue	UBERON:0007371	95.37	gold quality
body of tongue	UBERON:0011876	95.23	gold quality
pharyngeal mucosa	UBERON:0000355	95.17	gold quality
gluteal muscle	UBERON:0002000	95.03	gold quality
superficial temporal artery	UBERON:0001614	94.73	gold quality
skin of hip	UBERON:0001554	94.48	gold quality
oocyte	CL:0000023	94.38	gold quality
tongue	UBERON:0001723	94.36	gold quality
placenta	UBERON:0001987	94.00	gold quality
CA1 field of hippocampus	UBERON:0003881	93.79	gold quality
trigeminal ganglion	UBERON:0001675	93.78	gold quality
caput epididymis	UBERON:0004358	93.75	gold quality
seminal vesicle	UBERON:0000998	93.61	gold quality
cauda epididymis	UBERON:0004360	93.54	gold quality
corpus epididymis	UBERON:0004359	93.20	gold quality
cerebellar vermis	UBERON:0004720	93.19	gold quality
upper leg skin	UBERON:0004262	92.96	gold quality
saphenous vein	UBERON:0007318	92.89	gold quality
ventricular zone	UBERON:0003053	92.81	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.68	gold quality
penis	UBERON:0000989	92.44	gold quality
subthalamic nucleus	UBERON:0001906	92.44	gold quality
cartilage tissue	UBERON:0002418	92.43	gold quality
islet of Langerhans	UBERON:0000006	92.36	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.99
E-MTAB-6142	no	59.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

201 targeting TNKS2, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-23A-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 35)

• TNKS2 bound to Epstein-Barr virus origin of plasmid replication in coimmunoprecipitation experiments with transfected cell lysates. (PMID:15795250)
• pathologic overexpression of tankyrase 2 in some tumors may be a result of the cancer-related adaptation of the malignant cells dependent on tankyrase activity. (PMID:16151859)
• 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)
• pH dependence and kinetic study of the enzyme activity of tankyrase 2. (PMID:18393764)
• 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)
• Study reports crystal structures of a representative ankyrin repeat clusters of TNKS2 bound to targeting peptides from six substrates. (PMID:22153077)
• Data suggest that miR-20a can promote migration and invasion of cervical cancer cells through the upregulation of TNKS2. (PMID:22449978)
• 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)
• The variability of genes encoding for TERF1 and TNKS2 is important for keeping the integrity of the telomere structure and show a significant association with longevity. (PMID:25631672)
• Tankyrase inhibition is a potential therapeutic approach for treating a subgroup HCC with aberrant WNT/beta-catenin signaling pathway. (PMID:26246473)
• rs1340420 SNP was associated with lower NSCLC risk, whereas rs1770474 SNP was associated with higher squamous-cell carcinoma risk (PMID:26293798)
• Data show that E7449 represents a dual Poly(ADP-ribose) Polymerase 1/2 and tankyrase 1/2 inhibitor which has the advantage of targeting Wnt/beta-catenin signaling addicted tumors. (PMID:26513298)
• TNKS2 is recruited to DNA lesions by MDC1 and promotes homologous recombination in response to DNA double strand breaks. (PMID:26845027)
• These structural insights will be invaluable for the functional and biophysical characterization of TNKS1/2, including the role of TNKS oligomerization in protein poly(ADP-ribosyl)ation (PARylation) and PARylation-dependent ubiquitylation. (PMID:27328430)
• High TNKS2 expression is associated with breast cancer. (PMID:27485113)
• Polymerization is required for Tankyrase to drive beta-catenin-dependent transcription. The polymeric state supports PARP activity and allows Tankyrase to effectively access destruction complexes through enabling avidity-dependent AXIN binding. (PMID:27494558)
• The tumor suppressive activity of miR-490-3p is largely mediated through downregulation of TNKS2 and inactivation of beta-catenin signaling. Thus, miR-490-3p may represent a potential therapeutic target for triple-negative breast cancer. (PMID:27506313)
• Finally, through functional validation, we uncovered a role for TNKS/2 in peroxisome homeostasis and determined that this function is independent of TNKS enzyme activities. (PMID:28723574)
• Either tankyrase 1 or 2 is sufficient to maintain telomere length, but both are required to resolve telomere cohesion and maintain mitotic spindle integrity. Tankyrases are required for Notch2 to exit the plasma membrane and enter the nucleus to activate transcription. (PMID:29263426)
• CTIF was identified as a novel PARylation target of the TNKS2 in the centrosomal region of cells, which plays a role in the distribution of the centrosomal satellites. (PMID:29789535)
• The dimer is weak and may only form in the context of the sterile alpha motif (SAM )domain-mediated oligomers of TNKS2, consistent with the dependence of the TNKS2 activity on the SAM domain. (PMID:30055800)
• RP11-81H3.2 Acts as an Oncogene via microRNA-490-3p Inhibition and Consequential Tankyrase 2 Up-Regulation in Hepatocellular Carcinoma. (PMID:31858324)
• Regulation of poly ADP-ribosylation of VEGF by an interplay between PARP-16 and TNKS-2. (PMID:32472322)
• Association of Relative Leucocyte Telomere Length and Gene Single Nucleotide Polymorphisms (TERT, TRF1, TNKS2) in Laryngeal Squamous Cell Carcinoma. (PMID:32576588)
• A FRET-based high-throughput screening platform for the discovery of chemical probes targeting the scaffolding functions of human tankyrases. (PMID:32704068)
• MicroRNA-206 inhibits influenza A virus replication by targeting tankyrase 2. (PMID:33099847)
• Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1. (PMID:33361107)
• MicroRNA-490-3p inhibits migration and chemoresistance of colorectal cancer cells via targeting TNKS2. (PMID:33849554)
• Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex. (PMID:33923443)
• Mapping methylation quantitative trait loci in cardiac tissues nominates risk loci and biological pathways in congenital heart disease. (PMID:34112112)
• miR-582-5p inhibits migration and chemo-resistant capabilities of colorectal cancer cells by targeting TNKS2. (PMID:34357507)
• PARP5B is required for nonhomologous end joining during tumorigenesis in vivo. (PMID:34710250)
• Down-regulation of hsa_circ_0045474 induces macrophage autophagy in tuberculosis via miR-582-5p/TNKS2 axis. (PMID:34861798)
• Tankyrases inhibit innate antiviral response by PARylating VISA/MAVS and priming it for RNF146-mediated ubiquitination and degradation. (PMID:35733260)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tnks2	ENSMUSG00000024811
rattus_norvegicus	Tnks2	ENSRNOG00000052664
drosophila_melanogaster	Tnks	FBGN0027508
caenorhabditis_elegans	tnsl-1	WBGENE00010498

Paralogs (2): TNKS (ENSG00000173273), ANKRD45 (ENSG00000183831)

Protein

Protein identifiers

Poly [ADP-ribose] polymerase tankyrase-2 — Q9H2K2 (reviewed: Q9H2K2)

Alternative names: ADP-ribosyltransferase diphtheria toxin-like 6, Poly [ADP-ribose] polymerase 5B, Protein poly-ADP-ribosyltransferase tankyrase-2, TNKS-2, TRF1-interacting ankyrin-related ADP-ribose polymerase 2, Tankyrase II, Tankyrase-2, Tankyrase-like protein, Tankyrase-related protein

All UniProt accessions (2): Q9H2K2, A0AA34QVI1

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 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 poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. Stimulates 26S proteasome activity.

Subunit / interactions. Oligomerizes and associates with TNKS. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles. Binds to the N-terminus of Grb14 and TRF1 with its ankyrin repeat region. Interacts with HIF1AN. Interacts with RNF146; this interaction leads to ubiquitination and proteasomal degradation. Interacts with NUMA1.

Subcellular location. Cytoplasm. Golgi apparatus membrane. Nucleus. Chromosome. Telomere.

Tissue specificity. Highly expressed in placenta, skeletal muscle, liver, brain, kidney, heart, thymus, spinal cord, lung, peripheral blood leukocytes, pancreas, lymph nodes, spleen, prostate, testis, ovary, small intestine, colon, mammary gland, breast and breast carcinoma, and in common-type meningioma. Highly expressed in fetal liver, heart and brain.

Post-translational modifications. Ubiquitinated at ‘Lys-48’ and ‘Lys-63’ by RNF146 when auto-poly-ADP-ribosylated; this leads to degradation. Deubiquitinated by USP25; leading to stabilization. ADP-ribosylated (-auto). Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination. The crystallographic evidence suggests that the 3-hydroxyhistidine may be the (3S) stereoisomer.

Activity regulation. Specifically inhibited by XAV939, a small molecule, leading to inhibit the Wnt signaling pathway by stabilizing AXIN1 and AXIN2. Inhibited by talazoparib.

Similarity. Belongs to the ARTD/PARP family.

RefSeq proteins (1): NP_079511* (*=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, PF13637

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 (85 total): helix 24, repeat 15, strand 12, modified residue 10, turn 7, binding site 4, sequence conflict 4, mutagenesis site 3, domain 2, region of interest 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

197 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5BXO	X-RAY DIFFRACTION	1.33
5BXU	X-RAY DIFFRACTION	1.35
5NWG	X-RAY DIFFRACTION	1.4
5NWD	X-RAY DIFFRACTION	1.45
4PNL	X-RAY DIFFRACTION	1.5
5NVE	X-RAY DIFFRACTION	1.5
5NWC	X-RAY DIFFRACTION	1.5
7CE4	X-RAY DIFFRACTION	1.5
5JRT	X-RAY DIFFRACTION	1.53
3TWR	X-RAY DIFFRACTION	1.55
5C5R	X-RAY DIFFRACTION	1.55
5NVF	X-RAY DIFFRACTION	1.55
4TJU	X-RAY DIFFRACTION	1.57
4BUE	X-RAY DIFFRACTION	1.6
4BUU	X-RAY DIFFRACTION	1.6
4PNT	X-RAY DIFFRACTION	1.6
4UVZ	X-RAY DIFFRACTION	1.6
5NUT	X-RAY DIFFRACTION	1.6
5NVC	X-RAY DIFFRACTION	1.6
5NVH	X-RAY DIFFRACTION	1.6
5NWB	X-RAY DIFFRACTION	1.6
5NXE	X-RAY DIFFRACTION	1.6
8B6M	X-RAY DIFFRACTION	1.6
4BU9	X-RAY DIFFRACTION	1.65
4PNN	X-RAY DIFFRACTION	1.65
4PNS	X-RAY DIFFRACTION	1.65
4TK0	X-RAY DIFFRACTION	1.65
4UI5	X-RAY DIFFRACTION	1.65
3TWS	X-RAY DIFFRACTION	1.7
4L0V	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2K2-F1	84.76	0.63

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): 1081; 1084; 1089; 1092

Post-translational modifications (10): 203, 238, 271, 427, 518, 553, 586, 671, 706, 739

Mutagenesis-validated functional residues (3):

Position	Phenotype
553	enhanced hydroxylation by hif1an.
1054	loss of activity.

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: 267 (showing top): AHRARNT_01, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, TGCGCANK_UNKNOWN, GOBP_TELOMERE_CAPPING, GCANCTGNY_MYOD_Q6, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, YY1_Q6, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE

GO Biological Process (9): protein polyubiquitination (GO:0000209), Wnt signaling pathway (GO:0016055), positive regulation of telomere maintenance via telomerase (GO:0032212), 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)

GO Molecular Function (10): NAD+ poly-ADP-ribosyltransferase activity (GO:0003950), nucleotidyltransferase activity (GO:0016779), enzyme binding (GO:0019899), metal ion binding (GO:0046872), 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)

GO Cellular Component (11): Golgi membrane (GO:0000139), pericentriolar material (GO:0000242), chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nuclear envelope (GO:0005635), cytoplasm (GO:0005737), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), chromosome (GO:0005694), Golgi apparatus (GO:0005794), 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	5
cytoplasm	3
post-translational protein modification	2
pentosyltransferase activity	2
NAD+-protein mono-ADP-ribosyltransferase activity	2
intracellular membrane-bounded organelle	2
endomembrane system	2
protein ubiquitination	1
cell surface receptor signaling pathway	1
telomere maintenance via telomerase	1
regulation of telomere maintenance via telomerase	1
positive regulation of telomere maintenance via telomere lengthening	1
positive regulation of DNA biosynthetic 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
telomere capping	1
positive regulation of telomere maintenance	1
regulation of telomere capping	1
telomere maintenance via telomere lengthening	1
negative regulation of telomere maintenance	1
regulation of telomere maintenance via telomere lengthening	1
transferase activity, transferring phosphorus-containing groups	1
protein binding	1
cation binding	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
centrosome	1
chromosomal region	1
nucleus	1
organelle envelope	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2451 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNKS2	TERF1	P54274	992
TNKS2	AXIN1	O15169	976
TNKS2	CNOT12	Q9C0C2	926
TNKS2	GRB14	Q14449	802
TNKS2	RNF146	Q9NTX7	792
TNKS2	AXIN2	Q9Y2T1	787
TNKS2	CTNNB1	P35222	772
TNKS2	PARP1	P09874	770
TNKS2	SH3BP2	P78314	768
TNKS2	PARP2	Q9UGN5	739
TNKS2	PARP3	Q9Y6F1	695
TNKS2	HIF1AN	Q9NWT6	688
TNKS2	HNF4A	P41235	681
TNKS2	PARP16	Q8N5Y8	642
TNKS2	LNPEP	Q9UIQ6	630

IntAct

150 interactions, top by confidence:

A	B	Type	Score
TERF1	TNKS	psi-mi:“MI:0914”(association)	0.850
HIF1AN	APBA3	psi-mi:“MI:0914”(association)	0.850
TNKS2	HIF1AN	psi-mi:“MI:0407”(direct interaction)	0.800
HIF1AN	TNKS2	psi-mi:“MI:0210”(hydroxylation reaction)	0.800
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
TNKS2	TERF1	psi-mi:“MI:0915”(physical association)	0.790
TNKS2	TERF1	psi-mi:“MI:0407”(direct interaction)	0.790
BABAM1	TNKS2	psi-mi:“MI:0407”(direct interaction)	0.760
BABAM1	TNKS2	psi-mi:“MI:0915”(physical association)	0.760
TNKS2	Sh3bp2	psi-mi:“MI:0915”(physical association)	0.710
Sh3bp2	TNKS2	psi-mi:“MI:0915”(physical association)	0.710
TNKS2	Sh3bp2	psi-mi:“MI:0407”(direct interaction)	0.710
Sh3bp2	TNKS2	psi-mi:“MI:0407”(direct interaction)	0.710
TNKS2	HOXB2	psi-mi:“MI:0915”(physical association)	0.690
TNKS2	HOXB2	psi-mi:“MI:0407”(direct interaction)	0.690
TNKS2	DISC1	psi-mi:“MI:0407”(direct interaction)	0.690
TNKS2	NUMA1	psi-mi:“MI:0915”(physical association)	0.660
NUMA1	TNKS2	psi-mi:“MI:0407”(direct interaction)	0.660
TNKS2	ARPIN	psi-mi:“MI:0407”(direct interaction)	0.650

BioGRID (121): TNKS2 (Affinity Capture-MS), TNKS2 (Affinity Capture-MS), TNKS2 (Affinity Capture-MS), TNKS2 (Affinity Capture-MS), TNKS2 (Affinity Capture-MS), TNKS2 (Affinity Capture-MS), TNKS2 (Affinity Capture-Western), PTEN (Biochemical Activity), TNKS2 (Biochemical Activity), TNKS2 (Affinity Capture-MS), TNKS2 (Affinity Capture-MS), TNKS2 (Affinity Capture-MS), TNKS2 (Affinity Capture-MS), TNKS2 (Affinity Capture-MS), TNKS2 (Affinity Capture-MS)

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: A2ARS0, B2RXR6, C7B178, C9JTQ0, P0C927, P19838, Q00PJ3, Q07E43, Q08353, Q21920, Q29RM5, Q2QL84, Q337A0, Q3KP44, Q3SX00, Q3UES3, Q3UUF8, Q4FE45, Q4JHE0, Q4V890, Q502K3, Q5R8C8, Q5ZLC8, Q60J38, Q6KAE5, Q6TNT2, Q76K24, Q7EZ44, Q86W74, Q86WC6, Q8BTI7, Q8BTZ5, Q8C0T1, Q8NB46, Q8VHS5, Q9BSK4, Q9D119, Q9H2K2, Q9N3Q8, Q9Z2G1

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
TNKS2	“down-regulates quantity by destabilization”	AXIN1	ubiquitination
TNKS2	down-regulates	AXIN2	ubiquitination
XAV939	down-regulates	TNKS2	“chemical inhibition”
RNF146	“down-regulates quantity”	TNKS2	ubiquitination
TNKS2	“down-regulates quantity by destabilization”	GSK3B/Axin/APC
TNKS2	“up-regulates activity”	RNF146
TNKS2	“down-regulates quantity by destabilization”	AXIN1	ADP-ribosylation
TNKS2	“down-regulates quantity by destabilization”	AXIN2	ADP-ribosylation
TNKS2	“down-regulates quantity by destabilization”	CASC3	ADP-ribosylation
TNKS2	“down-regulates quantity by destabilization”	BLZF1	ADP-ribosylation
TNKS2	“down-regulates quantity by destabilization”	PSMF1	ADP-ribosylation
hsa-miR-1-3p	“down-regulates quantity by repression”	TNKS2	“post transcriptional regulation”
TNKS2	“up-regulates quantity by stabilization”	TARDBP	binding
XAV939	“down-regulates activity”	TNKS2	“chemical inhibition”
TNKS2	“down-regulates activity”	TERF1	ADP-ribosylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	93
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

4417 predictions. Top by Δscore:

Variant	Effect	Δscore
10:91798885:CGCAG:C	donor_loss	1.0000
10:91798886:GCAGG:G	donor_loss	1.0000
10:91798887:CAGGT:C	donor_loss	1.0000
10:91798888:AGGT:A	donor_loss	1.0000
10:91798889:GG:G	donor_loss	1.0000
10:91798890:G:T	donor_loss	1.0000
10:91798891:T:G	donor_loss	1.0000
10:91812978:T:G	acceptor_gain	1.0000
10:91812978:TCTA:T	acceptor_loss	1.0000
10:91812979:CTA:C	acceptor_loss	1.0000
10:91812980:TA:T	acceptor_loss	1.0000
10:91812981:A:AG	acceptor_gain	1.0000
10:91812981:AG:A	acceptor_gain	1.0000
10:91812982:G:GT	acceptor_gain	1.0000
10:91812982:GG:G	acceptor_gain	1.0000
10:91812982:GGT:G	acceptor_gain	1.0000
10:91812982:GGTT:G	acceptor_gain	1.0000
10:91812982:GGTTT:G	acceptor_gain	1.0000
10:91813187:G:GT	donor_gain	1.0000
10:91813188:A:T	donor_gain	1.0000
10:91813206:TGGTA:T	donor_loss	1.0000
10:91813208:G:GC	donor_loss	1.0000
10:91813208:G:GG	donor_gain	1.0000
10:91813209:T:A	donor_loss	1.0000
10:91817132:A:AG	acceptor_gain	1.0000
10:91817132:A:C	acceptor_loss	1.0000
10:91817132:AGT:A	acceptor_gain	1.0000
10:91817133:G:GG	acceptor_gain	1.0000
10:91817133:GT:G	acceptor_gain	1.0000
10:91817133:GTG:G	acceptor_gain	1.0000

AlphaMissense

7606 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:91798860:G:T	R57M	1.000
10:91798880:T:C	F64L	1.000
10:91798881:T:C	F64S	1.000
10:91798882:C:A	F64L	1.000
10:91798882:C:G	F64L	1.000
10:91798884:C:A	A65D	1.000
10:91812983:G:A	G67D	1.000
10:91812985:T:C	F68L	1.000
10:91812987:T:A	F68L	1.000
10:91812987:T:G	F68L	1.000
10:91812988:G:T	G69W	1.000
10:91812989:G:A	G69E	1.000
10:91812989:G:T	G69V	1.000
10:91812992:G:C	R70P	1.000
10:91813013:T:C	L77S	1.000
10:91813045:G:C	D88H	1.000
10:91813045:G:T	D88Y	1.000
10:91813046:A:C	D88A	1.000
10:91813046:A:T	D88V	1.000
10:91813058:T:A	L92H	1.000
10:91813058:T:C	L92P	1.000
10:91813072:A:G	N97D	1.000
10:91813074:T:A	N97K	1.000
10:91813074:T:G	N97K	1.000
10:91813079:G:A	C99Y	1.000
10:91813080:C:G	C99W	1.000
10:91813082:C:T	S100F	1.000
10:91813084:T:C	F101L	1.000
10:91813085:T:G	F101C	1.000
10:91813086:T:A	F101L	1.000

dbSNP variants (sampled 300 via entrez): RS1000031421 (10:91853321 G>A), RS1000054823 (10:91814097 A>C), RS1000090560 (10:91860658 T>G), RS1000101341 (10:91851982 A>G), RS1000123111 (10:91860171 C>T), RS1000144128 (10:91847440 C>T), RS1000152329 (10:91847208 G>T), RS1000306649 (10:91797644 T>C), RS1000380520 (10:91840308 C>T), RS1000473714 (10:91833561 A>G), RS1000479263 (10:91848693 T>A,G), RS1000487291 (10:91803673 G>GA), RS1000496753 (10:91804786 C>A), RS1000511232 (10:91853460 C>T), RS1000565959 (10:91803352 A>G)

Disease associations

OMIM: gene MIM:607128 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): CIC-rearranged sarcoma (MONDO:0956989)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST90000025_448	Appendicular lean mass	3.000000e-09
GCST90011900_59	Serum alkaline phosphatase levels	6.000000e-11
GCST90013406_107	Liver enzyme levels (alkaline phosphatase)	4.000000e-18
GCST90016666_3	Liver volume	7.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3038515 (PROTEIN FAMILY), CHEMBL6154 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 233,296 (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
CHEMBL521686	OLAPARIB	4	13,038
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL4112930	PAMIPARIB	3	2,114
CHEMBL506871	VELIPARIB	3	5,421
CHEMBL603469	LESTAURTINIB	3
CHEMBL3644587	2X-121	2	248
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL275638	FLAVONE	2	88,985
CHEMBL5095043	ATAMPARIB	1	246

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 5 [Tomassi et al., 2020]	Inhibition	9.52	pIC50
basroparib	Inhibition	8.49	pIC50
NVP‐TNKS656	Inhibition	8.22	pIC50
OM-1700	Inhibition	8.15	pIC50
AZ1366	Inhibition	8.0	pIC50
RK-287107	Inhibition	7.97	pIC50
compound 21 [PMID: 34141085]	Inhibition	7.2	pIC50
MC2050	Inhibition	6.71	pIC50

Binding affinities (BindingDB)

341 measured of 398 human assays (400 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
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-(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
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
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
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
3-[2-cyano-2-(6-oxo-7,8,9,10-tetrahydro-6aH-phenanthridin-3-yl)propyl]benzonitrile	IC50	0.933 nM	US-9598396: Tetrahydrophenanthridinones and tetrahydrocyclopentaquinolinones as PARP and tubulin polymerization inhibitors
3-(3-fluorophenyl)-2-methyl-2-(6-oxo-7,8,9,10-tetrahydro-6aH-phenanthridin-3-yl)propanenitrile	IC50	0.977 nM	US-9598396: Tetrahydrophenanthridinones and tetrahydrocyclopentaquinolinones as PARP and tubulin polymerization inhibitors
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
US10501467, Example 68	IC50	1.1 nM	US-9260440: Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors
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
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
N-[4-[5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl]cyclohexyl]-3-[(4-oxo-4aH-quinazolin-2-yl)sulfanyl]propanamide	IC50	1.52 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(4-cyanophenoxy)cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	2.23 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(4-chloro-3-cyanophenoxy)cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	2.33 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-pyridin-2-yloxycyclohexyl)butanamide	IC50	2.51 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(4-chlorophenoxy)cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	2.85 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(3-chlorophenoxy)cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	3.11 nM	US-9505749: Quinazolinone compounds and derivatives thereof
3-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)-N-[4-(2-oxo-1,3-benzoxazol-3-yl)cyclohexyl]propanamide	IC50	3.15 nM	US-9505749: Quinazolinone compounds and derivatives thereof

ChEMBL bioactivities

1341 potent at pChembl≥5 of 1385 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.32	IC50	0.048	nM	CHEMBL4646640
10.00	IC50	0.1	nM	CHEMBL4069447
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
9.80	IC50	0.16	nM	CHEMBL3805393
9.77	IC50	0.17	nM	CHEMBL3806163
9.74	IC50	0.18	nM	CHEMBL3805896
9.72	IC50	0.19	nM	CHEMBL3804939
9.72	IC50	0.19	nM	CHEMBL4634919
9.72	IC50	0.19	nM	CHEMBL5837355
9.70	IC50	0.2	nM	CHEMBL4098188
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
9.70	IC50	0.2	nM	CHEMBL6058768
9.69	IC50	0.2042	nM	CHEMBL4098188
9.68	IC50	0.21	nM	CHEMBL5855831
9.66	EC50	0.22	nM	CHEMBL3806163
9.66	IC50	0.22	nM	CHEMBL5816844
9.62	IC50	0.24	nM	CHEMBL6045415
9.60	IC50	0.25	nM	CHEMBL4632401
9.60	IC50	0.25	nM	CHEMBL5747945
9.59	EC50	0.26	nM	CHEMBL3805896
9.59	IC50	0.26	nM	CHEMBL4640008
9.57	IC50	0.27	nM	CHEMBL4643690
9.55	IC50	0.28	nM	CHEMBL3806049
9.54	IC50	0.29	nM	CHEMBL4639702
9.52	IC50	0.3	nM	CHEMBL4466701
9.52	IC50	0.3	nM	CHEMBL4581567
9.52	IC50	0.3	nM	CHEMBL4457037
9.52	IC50	0.3	nM	CHEMBL4544771
9.52	IC50	0.3	nM	CHEMBL4449082
9.52	IC50	0.3	nM	CHEMBL4638701
9.49	IC50	0.32	nM	CHEMBL5834126
9.48	IC50	0.33	nM	CHEMBL6019345
9.44	IC50	0.36	nM	CHEMBL6045512
9.43	IC50	0.37	nM	CHEMBL6016605
9.40	IC50	0.4	nM	CHEMBL3110106
9.40	IC50	0.4	nM	CHEMBL4525942
9.40	IC50	0.4	nM	CHEMBL6065828
9.39	IC50	0.41	nM	CHEMBL6008145
9.38	IC50	0.42	nM	CHEMBL4634146
9.36	IC50	0.44	nM	CHEMBL4645574
9.35	IC50	0.45	nM	CHEMBL5841231
9.35	IC50	0.45	nM	CHEMBL5884709
9.32	IC50	0.4786	nM	CHEMBL4101890

PubChem BioAssay actives

1012 with measured affinity, of 1771 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
4-[3-(8-methyl-4-oxo-3H-quinazolin-2-yl)propanoylamino]-N-quinolin-8-ylbenzamide	1436199: Inhibition of recombinant human N-terminal His-GST-tagged TNKS2 (849 to 1166 residues) expressed in baculovirus infected Sf9 cells using biotinylated NAD+ as substrate measured after 2 hrs	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	1299817: Inhibition of GST-tagged TNKS2 (873 to 1166 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	1299817: Inhibition of GST-tagged TNKS2 (873 to 1166 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	1299817: Inhibition of GST-tagged TNKS2 (873 to 1166 residues) (unknown origin) autoparsylation using biotinylated NAD incubated for 1 hr by ELISA	ic50	0.0002	uM
4-[3-(4-oxo-3H-quinazolin-2-yl)propanoylamino]-N-quinolin-8-ylbenzamide	1436199: Inhibition of recombinant human N-terminal His-GST-tagged TNKS2 (849 to 1166 residues) expressed in baculovirus infected Sf9 cells using biotinylated NAD+ as substrate measured after 2 hrs	ic50	0.0002	uM
2-[4-[4-(4-methoxy-3-methylbenzoyl)piperidin-1-yl]-4-oxobutyl]-7-methyl-3H-thieno[3,4-d]pyrimidin-4-one	1299817: Inhibition of GST-tagged TNKS2 (873 to 1166 residues) (unknown origin) autoparsylation using biotinylated NAD incubated for 1 hr by ELISA	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-[ethyl-[4-(1-methylindazole-6-carbonyl)piperidine-1-carbonyl]amino]benzoic acid	1666287: Inhibition of human GST-tagged tankyrase 2 autophosphorylation	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
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	1299817: Inhibition of GST-tagged TNKS2 (873 to 1166 residues) (unknown origin) autoparsylation using biotinylated NAD incubated for 1 hr by ELISA	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
2-[2-[4-[2-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]ethyl]piperazin-1-yl]ethylsulfanyl]-3H-quinazolin-4-one	1655635: Inhibition of full length human N-terminal GST-tagged TNKS2 ADP-ART catalytic domain (1001 to 1327 residues) using histone H2A as substrate incubated for 20 mins followed by [32P[-NAD+ addition and further incubated for 1 hr by liquid scintillation counter	ic50	0.0003	uM
4-[ethyl-[4-(3-methylbenzimidazole-5-carbonyl)piperidine-1-carbonyl]amino]benzoic acid	1666287: Inhibition of human GST-tagged tankyrase 2 autophosphorylation	ic50	0.0003	uM
4-[ethyl-[4-(1-methylindazole-5-carbonyl)piperidine-1-carbonyl]amino]benzoic acid	1666287: Inhibition of human GST-tagged tankyrase 2 autophosphorylation	ic50	0.0003	uM
6-[1-[ethyl-(4-methoxyphenyl)carbamoyl]piperidine-4-carbonyl]-1-methylindazole-3-carboxylic acid	1666287: Inhibition of human GST-tagged tankyrase 2 autophosphorylation	ic50	0.0003	uM
6-[1-[ethyl-(4-methoxyphenyl)carbamoyl]piperidine-4-carbonyl]-1-methylindole-2-carboxylic acid	1666287: Inhibition of human GST-tagged tankyrase 2 autophosphorylation	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
N-[4-(3-chloro-4-cyanophenoxy)cyclohexyl]-3-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]propanamide	1065802: Inhibition of TNKS2 (unknown origin) autoparsylation after 60 mins	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
5-[1-[ethyl-(4-methoxyphenyl)carbamoyl]piperidine-4-carbonyl]-1-methylindole-2-carboxylic acid	1666287: Inhibition of human GST-tagged tankyrase 2 autophosphorylation	ic50	0.0004	uM
2-[4-[6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-4-methyl-3-pyridinyl]phenyl]-7-methyl-3H-pyrrolo[2,3-d]pyrimidin-4-one	1428393: Inhibition of recombinant human TNKS2 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay	ic50	0.0005	uM
6-fluoro-2-[4-(2-hydroxypropan-2-yl)phenyl]-8-methyl-3H-quinazolin-4-one	1525647: Inhibition of GST tagged-TEV cleavage site-fused human recombinant TNKS2 (873 to 1166 residues) expressed in baculovirus infected sf9 cells assessed as reduction in auto-PARsylation incubated for 60 mins in presence of bio-NAD as co-substrate 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
6-fluoro-8-methyl-2-(4-piperidin-4-ylphenyl)-3H-quinazolin-4-one;hydrochloride	1525647: Inhibition of GST tagged-TEV cleavage site-fused human recombinant TNKS2 (873 to 1166 residues) expressed in baculovirus infected sf9 cells assessed as reduction in auto-PARsylation incubated for 60 mins in presence of bio-NAD as co-substrate by ELISA	ic50	0.0007	uM
N-[3-[5-(5-ethoxy-2-pyridinyl)-4-(5-methylthiophen-2-yl)-1,2,4-triazol-3-yl]cyclobutyl]-1,5-naphthyridine-4-carboxamide	1808137: Inhibition of recombinant human TNKS2 (873 to 1162 residues) incubated for 20 hrs in presence of NAD	ic50	0.0007	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
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
2-[4-(2-hydroxypropan-2-yl)phenyl]-7-methyl-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one	1925194: Inhibition of TNKS2 (unknown origin) using biotinylated NAD as substrate assessed as inhibition of autoPARsylation activity incubated for 1 hr by ELISA	ic50	0.0009	uM
4-fluoro-1-methyl-1’-(8-methyl-4-oxo-3,5,6,7-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-6-(4-methylpiperazin-1-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	0.0009	uM
3-[4-(2-hydroxypropan-2-yl)phenyl]-6-methyl-2H-pyrrolo[1,2-a]pyrazin-1-one	1866938: Inhibition of GST-tagged TNKS2 (873 - 1166 residues) (unknown origin) by ELISA	ic50	0.0009	uM
6-[4-[(5-oxo-2,3,4,4a,6,10b-hexahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-3-carbonitrile	1866926: Inhibition of TNKS2 (unknown origin)	ic50	0.0010	uM
3-[4-(1-hydroxycyclopropyl)phenyl]-6-methyl-2H-pyrrolo[1,2-a]pyrazin-1-one	1925194: Inhibition of TNKS2 (unknown origin) using biotinylated NAD as substrate assessed as inhibition of autoPARsylation activity incubated for 1 hr by ELISA	ic50	0.0010	uM
3-[4-[(2R)-2,4-dihydroxybutan-2-yl]phenyl]-6-methyl-2H-pyrrolo[1,2-a]pyrazin-1-one	1925194: Inhibition of TNKS2 (unknown origin) using biotinylated NAD as substrate assessed as inhibition of autoPARsylation activity incubated for 1 hr by ELISA	ic50	0.0010	uM
3-(2,3-dichlorophenyl)-N-(5,6-dihydro-[1,3]thiazolo[2,3-c][1,2,4]triazol-3-yl)propanamide	769661: Inhibition of N-terminal GST-tagged TNKS2 (unknown origin) expressed in baculovirus infected sf21 cells after 60 mins by LC-MS analysis	ic50	0.0010	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
methylmercuric chloride	increases expression, affects cotreatment	2
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects binding	2
dicrotophos	decreases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
IMOL S-140	increases expression	1
arsenite	decreases reaction, affects binding	1
zinc chromate	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
rucaparib	affects binding	1
jinfukang	decreases expression	1
XAV939	affects binding, decreases activity	1
IWR-1 compound	decreases activity, affects binding	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	increases mutagenesis	1
Succimer	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

225 unique, capped per target: 222 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
CHEMBL5723132	Functional	Affinity Biochemical interaction: (automodification of tankyrases with D+ as substrate, which is converted into a stable fluorescent condensation product) EUB0002225aCl TNKS2	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_TT17	HAP1 TNKS2 (-) 1	Cancer cell line	Male
CVCL_XU61	HAP1 TNKS2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02389244	PHASE2	ACTIVE_NOT_RECRUITING	A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas
NCT06414434	PHASE1	ACTIVE_NOT_RECRUITING	BTX-A51 in Patients With Liposarcoma or CIC-rearranged Sarcoma
NCT06820957	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing a New Combination of Anti-cancer Drugs in Patients Newly Diagnosed With Ewing Sarcoma Who Have Cancer That Has Spread to Other Parts of the Body