PARP2

Summary

PARP2 (poly(ADP-ribose) polymerase 2, HGNC:272) is a protein-coding gene on chromosome 14q11.2, encoding Poly [ADP-ribose] polymerase 2 (Q9UGN5). Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.

This gene encodes poly(ADP-ribosyl)transferase-like 2 protein, which contains a catalytic domain and is capable of catalyzing a poly(ADP-ribosyl)ation reaction. This protein has a catalytic domain which is homologous to that of poly (ADP-ribosyl) transferase, but lacks an N-terminal DNA binding domain which activates the C-terminal catalytic domain of poly (ADP-ribosyl) transferase. The basic residues within the N-terminal region of this protein may bear potential DNA-binding properties, and may be involved in the nuclear and/or nucleolar targeting of the protein. Two alternatively spliced transcript variants encoding distinct isoforms have been found.

Source: NCBI Gene 10038 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 96 total
• Druggable target: yes — 11 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001042618

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:272
Approved symbol	PARP2
Name	poly(ADP-ribose) polymerase 2
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	ARTD2
Ensembl gene	ENSG00000129484
Ensembl biotype	protein_coding
OMIM	607725
Entrez	10038

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000250416, ENST00000429687, ENST00000527384, ENST00000527915, ENST00000528465, ENST00000529465, ENST00000530598, ENST00000532299, ENST00000534664, ENST00000539930, ENST00000555140, ENST00000859467, ENST00000859468, ENST00000925414, ENST00000925415, ENST00000925416, ENST00000965371, ENST00000965372

RefSeq mRNA: 2 — MANE Select: NM_001042618 NM_001042618, NM_005484

CCDS: CCDS41910, CCDS45077

Canonical transcript exons

ENST00000429687 — 16 exons

Exon	Start	End
ENSE00000652570	20345394	20345464
ENSE00000652572	20346863	20346913
ENSE00000652574	20350526	20350622
ENSE00000652577	20351047	20351122
ENSE00000652580	20354809	20354947
ENSE00000652588	20357051	20357149
ENSE00000652590	20357396	20357520
ENSE00001124500	20357638	20357904
ENSE00001633883	20344932	20345087
ENSE00002146831	20343635	20343687
ENSE00003461934	20356307	20356434
ENSE00003518738	20355897	20356031
ENSE00003626094	20352245	20352347
ENSE00003657630	20354085	20354247
ENSE00003664358	20355752	20355815
ENSE00003693946	20356590	20356689

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 96.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.9618 / max 760.7416, expressed in 1783 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138421	18.9618	1783

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	96.49	gold quality
cerebellar cortex	UBERON:0002129	96.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.40	gold quality
cerebellum	UBERON:0002037	95.69	gold quality
right frontal lobe	UBERON:0002810	94.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.64	gold quality
ventricular zone	UBERON:0003053	93.59	gold quality
ganglionic eminence	UBERON:0004023	93.52	gold quality
prefrontal cortex	UBERON:0000451	93.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.20	gold quality
cortical plate	UBERON:0005343	92.99	gold quality
cerebellar vermis	UBERON:0004720	92.92	gold quality
left ovary	UBERON:0002119	92.84	gold quality
adenohypophysis	UBERON:0002196	92.76	gold quality
frontal cortex	UBERON:0001870	92.66	gold quality
neocortex	UBERON:0001950	92.59	gold quality
body of uterus	UBERON:0009853	92.50	gold quality
tibial nerve	UBERON:0001323	92.35	gold quality
cingulate cortex	UBERON:0003027	92.32	gold quality
right adrenal gland cortex	UBERON:0035827	92.24	gold quality
middle temporal gyrus	UBERON:0002771	92.22	gold quality
anterior cingulate cortex	UBERON:0009835	92.21	gold quality
primary visual cortex	UBERON:0002436	92.09	gold quality
right ovary	UBERON:0002118	92.04	gold quality
nucleus accumbens	UBERON:0001882	91.92	gold quality
body of pancreas	UBERON:0001150	91.91	gold quality
pituitary gland	UBERON:0000007	91.88	gold quality
right uterine tube	UBERON:0001302	91.82	gold quality
cerebral cortex	UBERON:0000956	91.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting PARP2, 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-513B-5P	99.99	69.96	2150
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-1288-5P	98.85	67.01	734
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-125B-2-3P	96.69	68.38	1210

Literature-anchored findings (GeneRIF, showing 40)

• PARP-1 and PARP-2 act as positive regulators of genomic stability in eukaryotic cells by counteracting topoisomerase I-induced DNA damage (PMID:14699148)
• PARP-2 and PARP-1 interact with TTF-1 and regulate the expression of surfactant protein B, a protein required for lung function (PMID:16461352)
• cells from old subjects show a constitutive expression level of both parp 1 and parp 2 genes reduced by a half (PMID:17518695)
• Determination of Poly (ADP-ribose) polymerase (PARP) homologues in human ejaculated sperm and its correlation with sperm maturation. (PMID:18339380)
• PARP-1-but not PARP-2-is required for proper expression of major genes involved in regulation of apoptosis (PMID:18587655)
• Results provide strong evidence that lysine 36 of PARP-2 is a critical residue for proper nuclear targeting of PARP-2 and consequently for the execution of its biological functions. (PMID:18644123)
• The histone subcode: poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 control cell differentiation by regulating the transcriptional intermediary factor TIF1beta and the heterochromatin protein HP1alpha (PMID:18676401)
• The PARP-2 gene might be associated with azoospermia by meiotic arrest (PMID:19806447)
• In complex with its inhibitor, the crystal structure of PARP2 alpha-helix 5 that contains glutamate residue Glu335 is closer to the active site than in both PARP1 and PARP3 and suggests a mechanism for a weak bias toward PARP2. (PMID:20092359)
• PARP-1 (but not PARP-2) poly(ADP) ribosylates Snail1, both in vivo and in vitro, and interacts with Snail1, an association that is sensitive to PARP inhibitors. (PMID:21577210)
• these findings propose a novel mechanism of PARP-2 in transcriptional regulation involving specific protein-protein interactions and highlight the importance of PARP-2 in the regulation of cell cycle progression. (PMID:23291187)
• the depletion of PARP-2 leads to lower HDL levels which represent a risk factor to cardiovascular diseases. (PMID:24365238)
• Nuclear Smad function is negatively regulated by PARP-1 that is assisted by PARP-2 and positively regulated by PARG during the course of TGFB signaling. (PMID:25133494)
• Interaction of PARP-2 with AP site containing DNA (PMID:25724268)
• Identification of ADP-ribosylation sites in PARP2 and the determination of the extent ofpoly(ADP-ribosyl)ated residues in this protein was performed. (PMID:25800440)
• 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)
• The initial affinity between the PARP1, PARP2 and the DNA damaged site appears to influence both the size of the Poly(ADP-Ribose) synthesized and the time of residence of PARylated PARP1 and PARP2 on DNA damages. (PMID:26673720)
• Our data suggest for the first time that a SNP in PARP2, rs878156, may together with other genetic variants modulate cancer specific survival in breast cancer patients depending on chemotherapy (PMID:26674097)
• Our study differentiates the functions of PARP-2 domains from those of PARP-1, the other major DDR-PARP, and highlights the specialization of the multi-domain architectures of DDR-PARPs. (PMID:26704974)
• Studies indicate that poly(ADP-ribose) polymerase 2 (PARP2) is involved in the differentiation of several cell types, including erythrocytes, T cells and adipocytes. (PMID:27087568)
• Findings indicate that Increased poly(ADP-ribose) polymerase-2 (PARP-2) expression and loss of micrRNA miR-149 expression are involved in the pathogenesis of hepatocellular carcinomas (HCC) and are poor prognosis factors in patients with HCC. (PMID:27300349)
• data further suggest that ARTD2 would function in double strand break repair as a dimeric module, while in single strand break repair it would function as a monomer. (PMID:27708353)
• either PARP1 or PARP2 are sufficient for near-normal XRCC1 recruitment at oxidative single-strand breaks (PMID:27965414)
• PARP2 specifically limits the accumulation of the resection barrier factor 53BP1 at DNA damage sites, allowing efficient CtIP-dependent DNA end-resection (PMID:29036662)
• Report a requirement for PARP2 in stabilizing replication forks that encounter base excision repair (BER) intermediates through Fbh1-dependent regulation of Rad51. Whereas PARP2 is dispensable for tolerance of cells to single stranded breaks or homologous recombination dysfunction, it is redundant with PARP1 in BER. (PMID:29467415)
• PARP2 is preferentially activated by poly(ADP-ribose) (PAR) and subsequently catalyzes branched PAR chain synthesis. (PMID:30104678)
• analysis of how ARTD2/PARP2 functions in DNA break recognition (PMID:30321391)
• The PARP2 plays under different physiological conditions, and reveal that PARP2 is tightly regulated by distinct pathways. (PMID:30880404)
• This study suggests that the functions of PARP1 and PARP2 overlap in DNA Base Excision Repair after a site cleavage and provides evidence for a role of PARP2 in the regulation of PARP1 activity. (PMID:31129062)
• PARP2 significantly higher expressed in primary prostate cancer (PC) tumors than in benign prostate, and even more so in castration-resistant PC. PARP-2, but not PARP-1, is a critical component in androgen receptor (AR)-mediated transcription through interacting with the pioneer factor FOXA1 and facilitating AR recruitment to genome-wide prostate-specific enhancer regions and regulation PC growth. (PMID:31266892)
• RPA directly binds activated PARP2 through poly(ADP-ribosyl)ation and can protect single-strand L1 integration intermediates from APOBEC3-mediated cytidine deamination in vitro. (PMID:31473101)
• HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation; as HPF1 forms a joint active site with PARP1 or PARP2, our data implicate HPF1 as an important determinant of the response to clinical PARP inhibitors (PMID:32028527)
• myeloid deletion of PARP2, but not PARP1, increases the population of immature myeloid cells in bone marrow, and impairs the expression of chemokines such as CCL3 through enhancing the transcriptional repression by beta-catenin. (PMID:32221289)
• Expression of poly-ADP-ribose polymerase (PARP) in endometrial adenocarcinoma: Prognostic potential. (PMID:32360251)
• Poly(ADP-Ribose) Polymerase Activity and Coronary Artery Disease in Type 2 Diabetes Mellitus: An Observational and Bidirectional Mendelian Randomization Study. (PMID:32757651)
• Progress and outlook in studying the substrate specificities of PARPs and related enzymes. (PMID:32785980)
• Bridging of DNA breaks activates PARP2-HPF1 to modify chromatin. (PMID:32939087)
• PARPs’ impact on base excision DNA repair. (PMID:33087277)
• Bridging of nucleosome-proximal DNA double-strand breaks by PARP2 enhances its interaction with HPF1. (PMID:33141820)
• The Oncogenic Helicase ALC1 Regulates PARP Inhibitor Potency by Trapping PARP2 at DNA Breaks. (PMID:33275888)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	parp2	ENSDARG00000079202
mus_musculus	Parp2	ENSMUSG00000036023
rattus_norvegicus	Parp2	ENSRNOG00000008892
caenorhabditis_elegans		WBGENE00004050

Paralogs (2): PARP3 (ENSG00000041880), PARP1 (ENSG00000143799)

Protein

Protein identifiers

Poly [ADP-ribose] polymerase 2 — Q9UGN5 (reviewed: Q9UGN5)

Alternative names: ADP-ribosyltransferase diphtheria toxin-like 2, DNA ADP-ribosyltransferase PARP2, NAD(+) ADP-ribosyltransferase 2, Poly[ADP-ribose] synthase 2, Protein poly-ADP-ribosyltransferase PARP2

All UniProt accessions (4): Q9UGN5, E9PJ27, G3V167, H0YH02

UniProt curated annotations — full annotation on UniProt →

Function. Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair. Mediates glutamate, aspartate or serine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2’-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1. Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP2 active site. PARP2 initiates the repair of double-strand DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones, thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks. HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP2 in order to limit the length of poly-ADP-ribose chains. Specifically mediates formation of branched poly-ADP-ribosylation. Branched poly-ADP-ribose chains are specifically recognized by some factors, such as APLF. In addition to proteins, also able to ADP-ribosylate DNA: preferentially acts on 5’-terminal phosphates at DNA strand breaks termini in nicked duplex.

Subunit / interactions. Component of a base excision repair (BER) complex, containing at least XRCC1, PARP1, POLB and LRIG3. Homo- and heterodimer with PARP1. Interacts (via the PARP catalytic domain) with HPF1. Interacts with core nucleosomes.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Widely expressed, mainly in actively dividing tissues. The highest levels are in the brain, heart, pancreas, skeletal muscle and testis; also detected in kidney, liver, lung, placenta, ovary and spleen; levels are low in leukocytes, colon, small intestine, prostate and thymus.

Post-translational modifications. Auto poly-ADP-ribosylated on serine residues, leading to dissociation of the PARP2-HPF1 complex from chromatin. Poly-ADP-ribosylated by PARP1. Acetylation reduces DNA binding and enzymatic activity. Proteolytically cleaved by caspase-8 (CASP8) in response to apoptosis, leading to its inactivation.

Activity regulation. ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism. In absence of activation signal, PARP2 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding. Activity is highly stimulated by signals, which unfold the PARP alpha-helical domain, relieving autoinhibition. Poly-ADP-ribosyltransferase activity is tightly regulated and PARP2 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences. CHD1L promotes PARP2 removal from chromatin. ADP-ribosyltransferase activity is inhibited by a number of PARP inhibitors (PARPi) compounds, that are used the treatment of breast or ovarian cancers that have defects in DNA repair by homologous recombination. PARPi molecules (niraparib, talazoparib, and, to a lesser extent, olaparib) also trap PARP2 at DNA damage sites.

Domain organisation. The N-terminal region (NTR) recognizes and binds poly-ADP-ribose chains produced by PARP1, leading to its recruitment to DNA damage sites. The N-terminal disordered region does not act as a key DNA-binding domain. The WGR and PARP catalytic domains function together to recruit PARP2 to sites of DNA breaks. The N-terminal disordered region is only required for activation on specific types of DNA damage. The WGR domain bridges two nucleosomes, with the broken DNA aligned in a position suitable for ligation. The bridging induces structural changes in PARP2 that signal the recognition of a DNA break to the catalytic domain of PARP2, promoting HPF1 recruitment and subsequent activation of PARP2, licensing serine ADP-ribosylation of target proteins. The PARP alpha-helical domain (also named HD region) prevents effective NAD(+)-binding in absence of activation signal. Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition.

Similarity. Belongs to the ARTD/PARP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UGN5-1	1	yes
Q9UGN5-2	2

RefSeq proteins (2): NP_001036083, NP_005475 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004102	Poly(ADP-ribose)pol_reg_dom	Domain
IPR008893	WGR_domain	Domain
IPR012317	Poly(ADP-ribose)pol_cat_dom	Domain
IPR036616	Poly(ADP-ribose)pol_reg_dom_sf	Homologous_superfamily
IPR036930	WGR_dom_sf	Homologous_superfamily
IPR050800	ARTD/PARP	Family

Pfam: PF00644, PF02877, PF05406

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), 3 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)
• L-seryl-[protein] + NAD(+) = O-(ADP-D-ribosyl)-L-seryl-[protein] + nicotinamide + H(+) (RHEA:58232)

UniProt features (96 total): strand 24, mutagenesis site 21, helix 19, sequence variant 6, binding site 4, modified residue 4, turn 4, domain 3, region of interest 2, sequence conflict 2, short sequence motif 2, chain 1, site 1, splice variant 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
4ZZX	X-RAY DIFFRACTION	1.65
5D5K	X-RAY DIFFRACTION	1.9
3KJD	X-RAY DIFFRACTION	1.95
3KCZ	X-RAY DIFFRACTION	2
7R59	X-RAY DIFFRACTION	2
4TVJ	X-RAY DIFFRACTION	2.1
8HKO	X-RAY DIFFRACTION	2.1
9IM8	X-RAY DIFFRACTION	2.1
9ZQB	ELECTRON MICROSCOPY	2.1
4ZZY	X-RAY DIFFRACTION	2.2
6F1K	X-RAY DIFFRACTION	2.2
8HLJ	X-RAY DIFFRACTION	2.24
9ZQC	ELECTRON MICROSCOPY	2.37
4PJV	X-RAY DIFFRACTION	2.5
8HKN	X-RAY DIFFRACTION	2.5
5DSY	X-RAY DIFFRACTION	2.7
8HLQ	X-RAY DIFFRACTION	2.7
6F5B	X-RAY DIFFRACTION	2.8
7AEO	X-RAY DIFFRACTION	2.8
8HKS	X-RAY DIFFRACTION	2.8
6TX3	X-RAY DIFFRACTION	2.96
6F5F	X-RAY DIFFRACTION	2.98
8HE8	X-RAY DIFFRACTION	3.05
8JNY	X-RAY DIFFRACTION	3.2
9ZQA	ELECTRON MICROSCOPY	3.28
9ZQ9	ELECTRON MICROSCOPY	3.3
6X0L	ELECTRON MICROSCOPY	3.9
6X0M	ELECTRON MICROSCOPY	6.3
6X0N	ELECTRON MICROSCOPY	10
6USJ	ELECTRON MICROSCOPY	10.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGN5-F1	82.82	0.64

Functional residue map

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

Catalytic / active sites (2): 207–208 (cleavage; by caspase-8); 558 (for poly [adp-ribose] polymerase activity)

Ligand- & substrate-binding residues (4): 428–430; 437; 444; 470

Post-translational modifications (4): 37, 38, 226, 232

Mutagenesis-validated functional residues (21):

Position	Phenotype
21–22	reduced localization to the nucleus. abolished localization to the nucleus; when associated with 37-a-a-38.
37–38	reduced localization to the nucleus. abolished localization to the nucleus; when associated with 21-a-a-22.
125–126	in parp2-qfrd mutant; induces conformational change that bridges nucleosomes by binding to linker dna ends and promotes
127	decreased poly [adp-ribose] polymerase activity. impaired formation of a complex with damaged dna.
128	does not affect poly [adp-ribose] polymerase activity.
129	reduced recruitment to dna damage sites. abolished dna-induced adp-ribosyltransferase activity.
130	decreased poly [adp-ribose] polymerase activity.
132	decreased poly [adp-ribose] polymerase activity.
151	decreased poly [adp-ribose] polymerase activity. impaired formation of a complex with damaged dna.
153	abolished formation of a complex with core nucleosome and hpf1, leading to abolished ability to catalyze serine adp-ribo
154	abolished formation of a complex with core nucleosome and hpf1, leading to abolished ability to catalyze serine adp-ribo
159	decreased poly [adp-ribose] polymerase activity.
183	decreased poly [adp-ribose] polymerase activity. impaired formation of a complex with damaged dna.
201	reduced dna-induced adp-ribosyltransferase activity.
201	reduced recruitment to dna damage sites. decreased poly [adp-ribose] polymerase activity.
286	increased dna-induced adp-ribosyltransferase activity.
338	does not affect dna-induced adp-ribosyltransferase activity.
394	strongly reduced serine adp-ribosylation, caused by abolished interaction with hpf1.
428	abolished trapping at dna damage sites upon binding to parp inhibitors (parpi).
558	abolished poly [adp-ribose] polymerase activity without affecting localization to dna damage sites.
582–583	strongly reduced serine adp-ribosylation, caused by abolished interaction with hpf1.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-110362	POLB-Dependent Long Patch Base Excision Repair
R-HSA-5685939	HDR through MMEJ (alt-NHEJ)
R-HSA-5696394	DNA Damage Recognition in GG-NER
R-HSA-5696395	Formation of Incision Complex in GG-NER
R-HSA-5696400	Dual Incision in GG-NER

MSigDB gene sets: 255 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, PID_TELOMERASE_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, KAUFFMANN_DNA_REPAIR_GENES, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, GOBP_DECIDUALIZATION, MODULE_118, BROWNE_HCMV_INFECTION_24HR_UP, GOBP_DNA_MODIFICATION

GO Biological Process (14): DNA repair (GO:0006281), base-excision repair (GO:0006284), double-strand break repair (GO:0006302), DNA damage response (GO:0006974), DNA ADP-ribosylation (GO:0030592), decidualization (GO:0046697), positive regulation of cell growth involved in cardiac muscle cell development (GO:0061051), protein poly-ADP-ribosylation (GO:0070212), protein auto-ADP-ribosylation (GO:0070213), response to oxygen-glucose deprivation (GO:0090649), extrinsic apoptotic signaling pathway (GO:0097191), hippocampal neuron apoptotic process (GO:0110088), DNA repair-dependent chromatin remodeling (GO:0140861), protein localization to chromatin (GO:0071168)

GO Molecular Function (17): chromatin binding (GO:0003682), damaged DNA binding (GO:0003684), NAD+ poly-ADP-ribosyltransferase activity (GO:0003950), nucleotidyltransferase activity (GO:0016779), nucleosome binding (GO:0031491), poly-ADP-D-ribose binding (GO:0072572), NAD DNA ADP-ribosyltransferase activity (GO:0140294), NAD+-protein-serine ADP-ribosyltransferase activity (GO:0140805), NAD+-protein-aspartate ADP-ribosyltransferase activity (GO:0140806), NAD+-protein-glutamate ADP-ribosyltransferase activity (GO:0140807), poly-ADP-D-ribose modification-dependent protein binding (GO:0160004), NAD+-protein mono-ADP-ribosyltransferase activity (GO:1990404), DNA binding (GO:0003677), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), site of DNA damage (GO:0090734), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	3
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1
Homology Directed Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pentosyltransferase activity	3
NAD+-protein mono-ADP-ribosyltransferase activity	3
cellular anatomical structure	3
DNA damage response	2
DNA repair	2
post-translational protein modification	2
binding	2
nuclear lumen	2
intracellular membraneless organelle	2
DNA metabolic process	1
cellular response to stress	1
DNA modification	1
maternal placenta development	1
developmental process involved in reproduction	1
tissue development	1
positive regulation of cardiac muscle hypertrophy	1
positive regulation of cell growth	1
positive regulation of striated muscle cell differentiation	1
positive regulation of cardiac muscle tissue growth	1
cell growth involved in cardiac muscle cell development	1
regulation of cell growth involved in cardiac muscle cell development	1
response to nutrient levels	1
response to decreased oxygen levels	1
cell surface receptor signaling pathway	1
apoptotic signaling pathway	1
neuron apoptotic process	1
chromatin remodeling	1
protein localization to chromosome	1
DNA binding	1
transferase activity, transferring phosphorus-containing groups	1
chromatin binding	1
protein-containing complex binding	1
carbohydrate derivative binding	1
ADP-D-ribose modification-dependent protein binding	1
catalytic activity, acting on a protein	1
nucleic acid binding	1
molecular_function	1
catalytic activity	1
transferase activity	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1835 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARP2	XRCC1	P18887	992
PARP2	LIG3	P49916	985
PARP2	POLB	P06746	976
PARP2	HPF1	Q9NWY4	945
PARP2	PARG	Q86W56	897
PARP2	BUB3	O43684	893
PARP2	CENPS	Q8N2Z9	801
PARP2	XRCC5	P13010	800
PARP2	CENPA	P49450	793
PARP2	PARP10	Q53GL7	766
PARP2	CENPB	P07199	765
PARP2	XRCC6	P12956	764
PARP2	APTX	Q7Z2E3	756
PARP2	TNKS	O95271	747
PARP2	TNKS2	Q9H2K2	739

IntAct

173 interactions, top by confidence:

A	B	Type	Score
XRCC6	XRCC5	psi-mi:“MI:0914”(association)	0.970
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
RPA4	RPA1	psi-mi:“MI:0914”(association)	0.740
POLB	XRCC1	psi-mi:“MI:0914”(association)	0.740
LIG3	XRCC1	psi-mi:“MI:0914”(association)	0.740
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
PARP2	APLF	psi-mi:“MI:0557”(adp ribosylation reaction)	0.690
HMGA1	H2AC21	psi-mi:“MI:0914”(association)	0.670
H2AC4	PPM1G	psi-mi:“MI:0914”(association)	0.670
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
MACROD1	PARP1	psi-mi:“MI:0914”(association)	0.620
PARP2	HMGN2	psi-mi:“MI:0557”(adp ribosylation reaction)	0.590
PARP2	STAC	psi-mi:“MI:0557”(adp ribosylation reaction)	0.560
PARP2	FKBP3	psi-mi:“MI:0557”(adp ribosylation reaction)	0.560

BioGRID (181): PARP2 (Affinity Capture-MS), PARP2 (Affinity Capture-MS), PARP2 (Affinity Capture-MS), PARP2 (Affinity Capture-MS), PARP2 (Affinity Capture-MS), PARP2 (Affinity Capture-MS), PARP2 (Affinity Capture-MS), PARP2 (Affinity Capture-MS), PARP2 (Proximity Label-MS), PARP2 (Proximity Label-MS), PARP2 (Affinity Capture-MS), PARP2 (Affinity Capture-MS), PARP2 (Affinity Capture-MS), PARP2 (Affinity Capture-MS), PARP2 (Affinity Capture-Western)

ESM2 similar proteins: A1A5P5, A2ARP1, A2VDY4, A7RS11, A8MVJ9, E7EXT2, F6S9E6, O70481, O88554, P06623, P09543, P09874, P0C644, P11103, P18493, P27008, P31669, Q0IHW8, Q14AI0, Q28651, Q32NQ7, Q4R7D0, Q5R5N9, Q5U2Z5, Q60996, Q66I84, Q66JD1, Q68F70, Q6DDS9, Q6GMB0, Q6GQ76, Q7EYV7, Q7SXS8, Q7SYB2, Q8CFE2, Q8CIM8, Q8IWV7, Q93YV6, Q96HW7, Q9BVC3

Diamond homologs: E1BSI0, O50017, O88554, P09874, P11103, P18493, P26446, P27008, P31669, P35875, Q08824, Q0JMY1, Q11207, Q11208, Q3ULW8, Q5RHR0, Q5Z8Q9, Q7EYV7, Q9R152, Q9UGN5, Q9Y6F1, Q9ZP54, Q9ZSV1, Q9N4H4, P49916, P97386, Q84JE8, Q0E0Q3, Q1SGF1, Q9FK91, Q9SWB4, Q9VBP3

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
veliparib	down-regulates	PARP2	“chemical inhibition”
1038915-60-4	down-regulates	PARP2	“chemical inhibition”
olaparib	down-regulates	PARP2	“chemical inhibition”
A-966492	down-regulates	PARP2	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 178 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SIRT1 negatively regulates rRNA expression	13	19.6×	2e-11
FXIIa activates plasma kallikrein-kinin system	12	18.4×	2e-10
RNA Polymerase I Promoter Opening	11	17.9×	1e-09
Packaging Of Telomere Ends	9	17.5×	3e-08
DNA methylation	11	17.4×	1e-09
Meiotic recombination	15	17.2×	4e-12
Replacement of protamines by nucleosomes in the male pronucleus	7	16.8×	2e-06
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	11	16.4×	3e-09

GO biological processes:

GO term	Partners	Fold	FDR
base-excision repair	9	26.5×	2e-08
heterochromatin formation	11	17.7×	2e-08
double-strand break repair via nonhomologous end joining	5	13.2×	4e-03
double-strand break repair	10	12.8×	2e-06
nucleotide-excision repair	5	12.0×	5e-03
telomere maintenance	7	11.8×	4e-04
nucleosome assembly	10	8.8×	6e-05
double-strand break repair via homologous recombination	7	6.9×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2040 predictions. Top by Δscore:

Variant	Effect	Δscore
14:20343741:A:T	donor_gain	1.0000
14:20345084:GATG:G	donor_gain	1.0000
14:20345097:G:GT	donor_gain	1.0000
14:20345098:A:T	donor_gain	1.0000
14:20345393:GA:G	acceptor_gain	1.0000
14:20346858:TCTAG:T	acceptor_loss	1.0000
14:20346859:CTA:C	acceptor_loss	1.0000
14:20346860:TAGGC:T	acceptor_loss	1.0000
14:20346861:A:AG	acceptor_gain	1.0000
14:20346861:AG:A	acceptor_gain	1.0000
14:20346862:G:A	acceptor_loss	1.0000
14:20346862:G:GA	acceptor_gain	1.0000
14:20346862:GG:G	acceptor_gain	1.0000
14:20346862:GGC:G	acceptor_gain	1.0000
14:20346862:GGCT:G	acceptor_gain	1.0000
14:20346862:GGCTC:G	acceptor_gain	1.0000
14:20346911:CAGG:C	donor_loss	1.0000
14:20346913:GGTA:G	donor_loss	1.0000
14:20346914:G:T	donor_loss	1.0000
14:20346915:T:G	donor_loss	1.0000
14:20350508:T:A	acceptor_gain	1.0000
14:20350515:A:AG	acceptor_gain	1.0000
14:20350516:C:G	acceptor_gain	1.0000
14:20350519:A:AG	acceptor_gain	1.0000
14:20350522:A:AG	acceptor_gain	1.0000
14:20350523:T:G	acceptor_gain	1.0000
14:20350524:A:AG	acceptor_gain	1.0000
14:20350525:G:GA	acceptor_gain	1.0000
14:20350525:GACC:G	acceptor_gain	1.0000
14:20350525:GACCA:G	acceptor_gain	1.0000

AlphaMissense

3773 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:20356600:T:A	W427R	0.999
14:20356600:T:C	W427R	0.999
14:20357051:T:C	F457L	0.999
14:20357053:T:A	F457L	0.999
14:20357053:T:G	F457L	0.999
14:20357089:G:C	K469N	0.998
14:20357089:G:T	K469N	0.998
14:20357060:G:A	G460R	0.997
14:20357060:G:C	G460R	0.997
14:20357072:G:C	A464P	0.997
14:20357085:C:T	S468F	0.997
14:20357090:A:C	S470R	0.997
14:20357092:T:A	S470R	0.997
14:20357092:T:G	S470R	0.997
14:20357094:C:A	A471D	0.997
14:20357104:C:G	C474W	0.997
14:20350569:T:C	L136P	0.996
14:20357061:G:A	G460E	0.996
14:20357484:G:A	G519D	0.996
14:20357718:A:T	E558V	0.996
14:20346906:T:C	L119P	0.995
14:20356323:T:C	L386P	0.995
14:20356603:C:G	H428D	0.995
14:20356607:G:A	G429D	0.995
14:20356624:T:A	W435R	0.995
14:20356624:T:C	W435R	0.995
14:20357051:T:A	F457I	0.995
14:20357055:G:T	G458V	0.995
14:20357085:C:A	S468Y	0.995
14:20357142:T:C	L487S	0.995

dbSNP variants (sampled 300 via entrez): RS1000267488 (14:20342361 C>A,T), RS1001171697 (14:20346734 T>A), RS1001497765 (14:20343190 T>C), RS1001524118 (14:20354533 C>G,T), RS1001551705 (14:20342703 C>G,T), RS1001776564 (14:20348786 G>A), RS1002100857 (14:20343392 T>C,G), RS1002228713 (14:20348526 C>G), RS1002504072 (14:20343447 C>G), RS1002556420 (14:20343414 G>A,C,T), RS1002818827 (14:20349864 A>G), RS1002840113 (14:20342731 T>C,G), RS1002951877 (14:20355456 A>C,G,T), RS1003531063 (14:20351667 C>T), RS1003710534 (14:20345556 C>G,T)

Disease associations

OMIM: gene MIM:607725 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005312_33	Menopause (age at onset)	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL3390820 (PROTEIN FAMILY), CHEMBL5169089 (PROTEIN-PROTEIN INTERACTION), CHEMBL5366 (SINGLE PROTEIN), CHEMBL6177907 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

11 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 41,090 (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
CHEMBL506871	VELIPARIB	3	5,421
CHEMBL4112930	PAMIPARIB	3	2,114
CHEMBL5095220	SARUPARIB	3	357
CHEMBL3644587	2X-121	2	248
CHEMBL4297461	CEP-9722	1	558
CHEMBL5095043	ATAMPARIB	1	246
CHEMBL5095223	AZD-9574	1	132

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 (10 total), top 10:

Ligand	Action	Affinity	Parameter
pamiparib	Inhibition	9.05	pIC50
olaparib	Inhibition	9.0	pIC50
niraparib	Binding	8.68	pIC50
PARP1 inhibitor (S)-G9	Inhibition	7.59	pIC50
compound 5 [Tomassi et al., 2020]	Inhibition	7.42	pIC50
compound 10b [PMID: 26222319]	Inhibition	6.9	pKd
AZ1366	Inhibition	6.63	pIC50
saruparib	Inhibition	5.82	pIC50
MC2050	Inhibition	5.74	pIC50
palacaparib	Inhibition	4.03	pIC50

Binding affinities (BindingDB)

202 measured of 257 human assays (257 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-(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
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
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-(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-(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-(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-[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
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-(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
N-[4-(3-cyanophenoxy)cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	3.26 nM	US-9505749: Quinazolinone compounds and derivatives thereof
3-[(4-amino-6-oxo-1,3-diazinan-2-yl)sulfanyl]-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclohexyl]propanamide	IC50	3.97 nM	US-9505749: Quinazolinone compounds and derivatives thereof
N-[4-(4-fluorophenoxy)cyclohexyl]-4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)butanamide	IC50	4.37 nM	US-9505749: Quinazolinone compounds and derivatives thereof
9,16,17-triazatetracyclo[8.7.1.02,8.014,18]octadeca-1,8,10,12,14(18),16-hexaen-15-one	IC50	4.9 nM	US-9328111: Substituted cycloocta[5,6]pyrido[4,3,2-de]phthalazines as PARP inhibitors
tert-butyl 14-oxo-5,8,15,16-tetrazatetracyclo[7.7.1.02,7.013,17]heptadeca-1,7,9,11,13(17),15-hexaene-5-carboxylate	IC50	5.1 nM	US-9328111: Substituted cycloocta[5,6]pyrido[4,3,2-de]phthalazines as PARP inhibitors
4-(4-oxo-2,3,4a,5,6,7,8,8a-octahydro-1H-quinazolin-2-yl)-N-(4-pyridin-4-yloxycyclohexyl)butanamide	IC50	5.1 nM	US-9505749: Quinazolinone compounds and derivatives thereof
US10501467, Example 19	IC50	5.2 nM	US-9260440: Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors
10,17,18-triazatetracyclo[9.7.1.02,9.015,19]nonadeca-1,9,11,13,15(19),17-hexaen-16-one	IC50	5.9 nM	US-9328111: Substituted cycloocta[5,6]pyrido[4,3,2-de]phthalazines as PARP inhibitors
US10501467, Example 6	IC50	6 nM	US-9260440: Fused tetra or penta-cyclic dihydrodiazepinocarbazolones as PARP inhibitors

ChEMBL bioactivities

1104 potent at pChembl≥5 of 1178 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	IC50	0.05	nM	CHEMBL5222013
10.00	IC50	0.1	nM	OLAPARIB
10.00	IC50	0.1	nM	CHEMBL5397373
9.96	IC50	0.11	nM	PAMIPARIB
9.96	IC50	0.11	nM	OLAPARIB
9.89	IC50	0.13	nM	OLAPARIB
9.70	IC50	0.2	nM	CHEMBL3984980
9.70	IC50	0.2	nM	TALAZOPARIB
9.66	IC50	0.22	nM	CHEMBL3907010
9.66	IC50	0.22	nM	CHEMBL5423934
9.62	IC50	0.24	nM	CHEMBL5421335
9.59	IC50	0.26	nM	CHEMBL5423161
9.57	Kd	0.27	nM	OLAPARIB
9.55	Kd	0.28	nM	OLAPARIB
9.54	IC50	0.29	nM	CHEMBL5439635
9.52	IC50	0.3	nM	CHEMBL3933450
9.52	IC50	0.3	nM	CHEMBL3926240
9.52	IC50	0.3	nM	CHEMBL3922789
9.52	IC50	0.3	nM	CHEMBL3929889
9.52	IC50	0.3	nM	CHEMBL3975917
9.52	IC50	0.3	nM	TALAZOPARIB
9.52	IC50	0.3	nM	PAMIPARIB
9.52	IC50	0.3	nM	CHEMBL5420649
9.52	IC50	0.3	nM	OLAPARIB
9.49	IC50	0.32	nM	CHEMBL5182405
9.48	IC50	0.33	nM	CHEMBL5419831
9.48	IC50	0.33	nM	CHEMBL5416806
9.42	IC50	0.38	nM	CHEMBL5432851
9.40	IC50	0.4	nM	CHEMBL4107982
9.40	IC50	0.3981	nM	OLAPARIB
9.40	IC50	0.4	nM	OLAPARIB
9.40	IC50	0.4	nM	RUCAPARIB
9.36	IC50	0.44	nM	CHEMBL5432860
9.35	IC50	0.45	nM	OLAPARIB
9.31	IC50	0.49	nM	CHEMBL2323226
9.31	IC50	0.49	nM	CHEMBL5394020
9.30	IC50	0.5	nM	CHEMBL3955609
9.30	IC50	0.5	nM	PAMIPARIB
9.30	IC50	0.5	nM	CHEMBL3901232
9.30	IC50	0.5	nM	OLAPARIB
9.30	IC50	0.5	nM	RUCAPARIB
9.30	Kd	0.5	nM	OLAPARIB
9.24	IC50	0.58	nM	TALAZOPARIB
9.22	IC50	0.6	nM	CHEMBL3972156
9.22	IC50	0.6	nM	TALAZOPARIB
9.21	IC50	0.62	nM	CHEMBL5423072
9.19	IC50	0.6457	nM	CHEMBL4529965
9.19	IC50	0.64	nM	CHEMBL5080271
9.15	IC50	0.7	nM	CHEMBL3914932
9.15	IC50	0.7	nM	CHEMBL3901034

PubChem BioAssay actives

787 with measured affinity, of 1403 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
4-[[3-[3-(5-bromofuran-2-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one	2012695: Inhibition of PARP2 (unknown origin) using histone as substrate by ELISA	ic50	<0.0001	uM
(2R)-14-fluoro-2-methyl-6,9,10,19-tetrazapentacyclo[14.2.1.02,6.08,18.012,17]nonadeca-1(18),8,12(17),13,15-pentaen-11-one	1949554: Inhibition of PARP-2 (unknown origin)	ic50	0.0001	uM
ethyl N-[6-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]phenyl]-1H-benzimidazol-2-yl]carbamate	2115914: Inhibition of PARP2 (unknown origin)	ic50	0.0001	uM
1-[[3-[4-(cyclopentylmethyl)-3-oxopiperazine-1-carbonyl]-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0001	uM
Olaparib	1896631: Inhibition of PARP-2 (unknown origin)	ic50	0.0001	uM
Talazoparib	1909173: Inhibition of PARP2 (unknown origin) using NAD as substrate incubated for 1 min	ic50	0.0002	uM
1-[[3-[4-(1-cyclopentylethyl)-3-oxopiperazine-1-carbonyl]-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0002	uM
1-[[3-[4-(cyclohexylmethyl)-3-oxopiperazine-1-carbonyl]-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0002	uM
3,3-dimethyl-16-(2-piperidin-1-ylethyl)-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0002	uM
4-[[4-fluoro-3-[5-methyl-3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	1638269: Inhibition of recombinant human PARP2 using histone as substrate after 1 hr in presence of NAD+ by ELISA	ic50	0.0002	uM
2-[[1-(2-chloroacetyl)-3,4-dihydro-2H-quinolin-6-yl]oxy]-N-[10-[4-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]-10-oxodecyl]acetamide	1908537: Inhibition of PARP2 (unknown origin)	ic50	0.0003	uM
4-[[4-fluoro-3-[(5R)-5-methyl-3-(1,3-thiazol-2-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	2019974: Inhibition of PARP2 (unknown origin) by ELISA assay	ic50	0.0003	uM
1-[[3-(4-cyclohexyl-3-oxopiperazine-1-carbonyl)-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0003	uM
1-[[3-[4-(1-cyclohexylethyl)-3-oxopiperazine-1-carbonyl]-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0003	uM
1-[[3-[4-(2,2-dimethylpropyl)-3-oxopiperazine-1-carbonyl]-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0003	uM
1-[[3-(4-cyclopentyl-3-oxopiperazine-1-carbonyl)-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0003	uM
16-[2-(dimethylamino)ethyl]-3,3-dimethyl-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0003	uM
16-[2-(diethylamino)ethyl]-3,3-dimethyl-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0003	uM
16-[2-(dimethylamino)ethyl]-11-fluoro-3,3-dimethyl-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0003	uM
1-[[4-fluoro-3-[4-(2-methylpropyl)-3-oxopiperazine-1-carbonyl]phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0004	uM
1-[[3-(4-butan-2-yl-3-oxopiperazine-1-carbonyl)-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0004	uM
Rucaparib	1909171: Inhibition of PARP2 (unknown origin)	ic50	0.0004	uM
1-[[3-(4-butyl-3-oxopiperazine-1-carbonyl)-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0005	uM
5-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]-5-azatricyclo[6.3.1.04,12]dodeca-1(11),8(12),9-trien-2-one	728422: Inhibition of PARP1/PARP2 in human SKOV3 cells assessed as reduction in H2O2-induced PARylation incubated for 4 hrs prior to H2O2 treatment	ic50	0.0005	uM
1-[[4-fluoro-3-[(3R)-3-methyl-4-(2-methylpropanoyl)piperazine-1-carbonyl]phenyl]methyl]quinazoline-2,4-dione	1830903: Inhibition of recombinant human PARP2 using NAD+ as substrate incubated for 1 hr by ELISA	ic50	0.0006	uM
3,3-dimethyl-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0006	uM
2-[2-[[4-[(Z)-(7-carbamoyl-3-oxo-1-benzofuran-2-ylidene)methyl]benzoyl]amino]ethyl]-1H-benzimidazole-4-carboxamide	1508854: Inhibition of human N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 insect cells using histone as substrate measured after 1 hr by horseradish peroxidase-coupled chemiluminescence assay	ic50	0.0006	uM
1-[[4-fluoro-3-(3-oxo-4-phenylpiperazine-1-carbonyl)phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0006	uM
3-fluoro-7,8,17-triazatetracyclo[12.2.1.05,16.09,15]heptadeca-1,3,5(16),8,14-pentaen-6-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0007	uM
11-fluoro-3-propan-2-yl-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0007	uM
1-[[4-fluoro-3-(3-oxo-4-prop-2-enylpiperazine-1-carbonyl)phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0007	uM
11-fluoro-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0008	uM
3-propan-2-yl-3,6,7,16-tetrazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0008	uM
1-[[4-fluoro-3-(3-oxo-4-pentan-3-ylpiperazine-1-carbonyl)phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0008	uM
1-[[4-fluoro-3-[4-(2-methoxyethyl)-3-oxopiperazine-1-carbonyl]phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0008	uM
1-[[3-(4-benzyl-3-oxopiperazine-1-carbonyl)-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0008	uM
4-[[3-[4-[[2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one	1758282: Inhibition of PARP2 (unknown origin) using biotin-NAD+ as substrate incubated for 1 hr by ELISA	ic50	0.0009	uM
2-[4-[[2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazine-1-carbonyl]-1-benzofuran-7-carboxamide	1758282: Inhibition of PARP2 (unknown origin) using biotin-NAD+ as substrate incubated for 1 hr by ELISA	ic50	0.0009	uM
sodium 1-[[4-fluoro-3-(3-oxo-4-pentan-3-ylpiperazine-1-carbonyl)phenyl]methyl]quinazolin-3-ide-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0009	uM
1-[[4-fluoro-3-[4-(3-methylbutyl)-3-oxopiperazine-1-carbonyl]phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0009	uM
1-[[4-fluoro-3-(3-oxo-4-pentylpiperazine-1-carbonyl)phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0009	uM
11-(1,3-dihydroisoindol-2-ylmethyl)-2,3,10,12-tetrazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8,11-pentaen-4-one	1424648: Inhibition of recombinant human PARP2 using DNase I-activated herring sperm DNA and [3H]nicotinamide after 2 mins by scintillation counting method	ic50	0.0010	uM
3-(2-amino-2-methylpropanoyl)-3,6,7,16-tetrazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0010	uM
(3S)-1-(2-cyclopropylethyl)-N-[5-[(2,4-dioxoquinazolin-1-yl)methyl]-2-fluoro-3-pyridinyl]pyrrolidine-3-carboxamide	1486468: Inhibition of recombinant human PARP-2 expressed in Escherichia coli BL21 (DE3) using sheared DNA as substrate in presence of biotinylated NAD after 1 hr by ELISA	ic50	0.0010	uM
2-(4-piperidin-4-ylphenyl)-1H-benzimidazole-4-carboxamide	475222: Inhibition of PARP2 by top count scintillation counting	ki	0.0010	uM
2-[4-[[4-[(2-aminophenyl)carbamoyl]phenyl]methylamino]phenyl]-1H-benzimidazole-4-carboxamide	2108844: Inhibition of PARP2 (unknown origin) using histone/NAD+ as substrates by NAD/NADH-Glo assay	ic50	0.0010	uM
2-(3-pyrazin-2-ylpropanoyl)-2,11-diazatricyclo[7.3.1.05,13]trideca-5(13),6,8-trien-10-one	455968: Inhibition of PARP2	ic50	0.0010	uM
2-(2-pyridin-3-ylacetyl)-2,11-diazatricyclo[7.3.1.05,13]trideca-5(13),6,8-trien-10-one	455968: Inhibition of PARP2	ic50	0.0010	uM
2-(4-pyridin-4-ylphenyl)-1H-benzimidazole-4-carboxamide	475222: Inhibition of PARP2 by top count scintillation counting	ki	0.0010	uM
2-[4-[3-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]pyridine-3-carbonitrile	1265290: Inhibition of human PARP2 (2 to 583 residues) expressed in Baculovirus infected Sf9 insect cells using activated DNA as substrate after 1 hr by streptavidin-horseradish peroxidase-based luminescence assay	ic50	0.0010	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
veliparib	affects binding, decreases activity	4
bisphenol A	increases expression, affects cotreatment, increases methylation, decreases expression	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects binding, decreases activity	2
Cisplatin	increases expression	2
FR900359	decreases phosphorylation	1
lasiocarpine	increases expression	1
triphenyl phosphate	affects expression	1
cypermethrin	increases expression	1
3-aminobenzamide	affects binding	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
deguelin	increases expression	1
tanespimycin	increases expression	1
CPG-oligonucleotide	decreases expression	1
K 7174	decreases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
pyrachlostrobin	increases expression	1
5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide	increases expression	1
rucaparib	decreases activity	1
olaparib	decreases activity, affects binding	1
STA 9090	increases expression	1
XAV939	decreases activity	1
niraparib	decreases activity, affects binding	1
(+)-JQ1 compound	decreases expression	1
talazoparib	decreases activity	1
Resveratrol	affects cotreatment, increases expression	1

ChEMBL screening assays

241 unique, capped per target: 233 binding, 5 functional, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1115416	Binding	Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inhibition DNA-damage-induced PARylation	Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. — J Med Chem
CHEMBL3429724	Functional	Inhibition of PARP activity in tumor of immunocompromised mouse xenografted with human MDA-MB-436 cells harboring BRCA1 mutant assessed as incorporation of [3H]NAD in PAR chains in response to nicked DNA at 50 to 100 mg/kg, po measured afte	Niraparib: A Poly(ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination. — J Med Chem
CHEMBL4345423	ADMET	Inhibition of human recombinant N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 cells assessed as reduction in auto-PARylation using histone as substrate measured after 45 mins in presence of biotinylat	Design and Discovery of an Orally Efficacious Spiroindolinone-Based Tankyrase Inhibitor for the Treatment of Colon Cancer. — J Med Chem

Cellosaurus cell lines

10 cell lines: 8 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3DG	Abcam HEK293T PARP2 KO	Transformed cell line	Female
CVCL_C0BR	Abcam U2OS PARP2 KO	Cancer cell line	Female
CVCL_D7WL	Ubigene A-549 PARP2 KO	Cancer cell line	Male
CVCL_E1IX	HyCyte A-549 KO-hPARP2	Cancer cell line	Male
CVCL_KT90	HeLa SilenciX PARP2	Cancer cell line	Female
CVCL_RR04	MCF10A PARP2 (-/-)	Spontaneously immortalized cell line	Female
CVCL_TC15	HAP1 PARP2 (-) 1	Cancer cell line	Male
CVCL_TC16	HAP1 PARP2 (-) 2	Cancer cell line	Male
CVCL_XR37	HAP1 PARP2 (-) 3	Cancer cell line	Male
CVCL_XR38	HAP1 PARP2 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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