PARP1

gene

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Also known as PARPARTD1Poly-PARPPARS

Summary

PARP1 (poly(ADP-ribose) polymerase 1, HGNC:270) is a protein-coding gene on chromosome 1q42.12, encoding Poly [ADP-ribose] polymerase 1 (P09874). Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair. In precision oncology, PARP1 OVEREXPRESSION confers sensitivity to Olaparib in Malignant Peripheral Nerve Sheath Tumor (CIViC Level D); 2 further curated variant–drug associations are listed below.

This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes.

Source: NCBI Gene 142 — RefSeq curated summary.

At a glance

Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
GWAS associations: 10
Clinical variants (ClinVar): 117 total
Druggable target: yes — 24 molecules with ChEMBL bioactivity
Precision-oncology evidence (CIViC): 3 curated variant–drug associations
Transcription factor: yes — 152 downstream targets (CollecTRI)
MANE Select transcript: NM_001618

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:270
Approved symbol	PARP1
Name	poly(ADP-ribose) polymerase 1
Location	1q42.12
Locus type	gene with protein product
Status	Approved
Aliases	PARP, ARTD1, Poly-PARP, PARS
Ensembl gene	ENSG00000143799
Ensembl biotype	protein_coding
OMIM	173870
Entrez	142

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 15 retained_intron, 13 protein_coding, 6 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000366790, ENST00000366792, ENST00000366794, ENST00000463968, ENST00000468608, ENST00000469663, ENST00000490921, ENST00000491816, ENST00000498787, ENST00000676481, ENST00000676565, ENST00000676685, ENST00000676709, ENST00000677091, ENST00000677189, ENST00000677203, ENST00000677374, ENST00000677815, ENST00000677884, ENST00000677985, ENST00000678144, ENST00000678226, ENST00000678288, ENST00000678560, ENST00000678781, ENST00000679276, ENST00000874606, ENST00000874607, ENST00000874608, ENST00000874609, ENST00000922077, ENST00000922078, ENST00000922079, ENST00000922080, ENST00000922081, ENST00000963780, ENST00000963781

RefSeq mRNA: 1 — MANE Select: NM_001618 NM_001618

CCDS: CCDS1554

Canonical transcript exons

ENST00000366794 — 23 exons

Exon	Start	End
ENSE00000962007	226402214	226402379
ENSE00000962010	226388656	226388755
ENSE00000962011	226386326	226386442
ENSE00000962012	226385504	226385680
ENSE00000962013	226383036	226383183
ENSE00000962014	226381068	226381208
ENSE00000962015	226379922	226380164
ENSE00000962016	226379573	226379641
ENSE00000962017	226379142	226379274
ENSE00000962018	226377108	226377303
ENSE00000962019	226374226	226374354
ENSE00000962020	226370434	226370517
ENSE00001442633	226360691	226361541
ENSE00001697768	226407810	226408093
ENSE00003476295	226361969	226362083
ENSE00003492408	226365954	226366052
ENSE00003498847	226365002	226365154
ENSE00003548024	226392199	226392314
ENSE00003550925	226390410	226390624
ENSE00003576366	226367480	226367608
ENSE00003595606	226363943	226364070
ENSE00003634072	226368199	226368321
ENSE00003642486	226363099	226363160

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 98.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.7033 / max 732.0343, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17753	57.7983	1819
17752	2.1437	968
201973	1.7129	864
17751	1.0484	529

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.57	gold quality
ganglionic eminence	UBERON:0004023	98.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.15	gold quality
embryo	UBERON:0000922	97.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.23	gold quality
spinal cord	UBERON:0002240	96.92	gold quality
lymph node	UBERON:0000029	96.73	gold quality
middle frontal gyrus	UBERON:0002702	96.46	gold quality
cortical plate	UBERON:0005343	96.28	gold quality
vermiform appendix	UBERON:0001154	96.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.05	gold quality
corpus callosum	UBERON:0002336	95.95	gold quality
apex of heart	UBERON:0002098	95.72	gold quality
amygdala	UBERON:0001876	95.59	gold quality
caecum	UBERON:0001153	95.52	gold quality
islet of Langerhans	UBERON:0000006	95.50	gold quality
heart left ventricle	UBERON:0002084	95.40	gold quality
spleen	UBERON:0002106	95.36	gold quality
cardiac ventricle	UBERON:0002082	95.29	gold quality
prefrontal cortex	UBERON:0000451	95.28	gold quality
body of pancreas	UBERON:0001150	95.27	gold quality
putamen	UBERON:0001874	95.06	gold quality
inferior vagus X ganglion	UBERON:0005363	95.01	gold quality
caudate nucleus	UBERON:0001873	94.82	gold quality
adenohypophysis	UBERON:0002196	94.80	gold quality
pancreas	UBERON:0001264	94.72	gold quality
bone marrow cell	CL:0002092	94.64	gold quality
pituitary gland	UBERON:0000007	94.52	gold quality
tonsil	UBERON:0002372	94.52	gold quality
right frontal lobe	UBERON:0002810	94.52	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	127.89
E-HCAD-4	yes	51.72
E-CURD-112	yes	42.05
E-GEOD-134144	yes	29.38
E-CURD-122	yes	21.50
E-HCAD-10	yes	13.39
E-ANND-3	yes	12.46
E-MTAB-10042	yes	4.32
E-MTAB-9801	yes	3.91
E-ENAD-17	no	1459.14

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

152 targets.

Target	Regulation
ACP3
AGTR2
AIFM1
APOD
AR
B3GNT9
BCL2	Repression
BCL2L1
BIN1
BIRC3
BIRC5
BRCA1
BRCA2	Repression
CASP1
CASP3
CASP4
CASP7
CASP8
CASP9
CAT
CCND1
CD74
CDH1	Activation
CDH17
CDK4
CDK8
CDKN1A	Unknown
CDKN1B
CDKN2A
CEL

Upstream regulators (CollecTRI, top): AR, EP300, ETS1, FLT3, MYBL2, MYC, NFATC2, NFKB, PARP1, PAX3, PGR, RELA, SP1, SP3, TP53, YY1

miRNA regulators (miRDB)

58 targeting PARP1, 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-4668-3P	100.00	68.74	2635
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868

Literature-anchored findings (GeneRIF, showing 40)

Here, we show that PARP activation reaction in vitro becomes acidic with release of protons during hydrolysis of beta-nicotinamide adenine dinucleotide (PMID:11756665)
PARP co-activates B-MYB through enhanced phosphorylation at cyclin/cdk2 sites (PMID:11781832)
PARP-1 degradation in etoposide-treated apoptotic cells may precede DNA cleavage. (PMID:11846007)
PARP expression in Ewing’s sarcoma cells (PMID:11956622)
Escherichia coli shiga-like toxins induce apoptosis and cleavage of poly(ADP-ribose) polymerase via in vitro activation of caspases (PMID:12117981)
TRAIL treatment did not result in PARP cleavage. (PMID:12496481)
PARP immunoreactivity is increased 3-fold in spinal cord tissues of sporadic amyotrophic lateral sclerosis (sALS) patients compared with non-neurological disease controls, demonstrating a role of glial alterations in sALS pathogenesis. (PMID:12528821)
Inhibition of BRCA1 via overexpressing the RHA fragment coincides with a reduction in PARP-1 protein expression. PARP-1 is identified as a downstream effector of BRCA1 function in the maintenance of genomic stability. (PMID:12592385)
Poly(ADP-ribose) polymerase activation and changes in Bax protein expression associated with extracellular ATP-mediated apoptosis in human embryonic kidney 293-P2X7 cells. (PMID:12606781)
PARP-1 haplotypes play a role in susceptibility to rheumatoid arthritis. (PMID:12632415)
study establishes poly(ADP-ribose) polymerase-1 as a critical regulator of the protein p53 response to DNA damage (PMID:12642583)
Translocation of this protein was used to monitor the partial purification of the active components(s) from both human T cell and yeast extracts. (PMID:12668662)
PARP-1 does not play a major role in catalysis of DNA damage processing via either base excision repair pathway. (PMID:12673357)
polyADP ribosyl transferase level is linked with the oxidoreduction reactions seen in Fanconi anemia (PMID:12674511)
examination of binding of central and carboxy-terminal regions p53 protein (PMID:12704785)
centenarian subjects display low MTmRNA, good zinc ion bioavailability, satisfactory NK cell activity and higher capacity of PARP-1 in base excision DNA-repair. (PMID:12714254)
in the peripheral blood, appears to be present at higher rates in COPD patients than in healthy age-matched controls (PMID:12853070)
PARP-1 and p21 could cooperate in regulating the functions of PCNA during DNA replication/repair. (PMID:12930846)
PARP-1 acts synergistically with p300 and plays an essential regulatory role in NF-kappaB-dependent gene expression (PMID:12960163)
reduced blood flow and subsequent ischemic damages in leiomyoma could be responsible for PARP overexpression and PAR accumulation, clinical response, and tumor degeneration caused by leuprorelin treatment. (PMID:14557488)
cellular poly(ADP-ribose) polymerase 1 (PARP-1) and Ste20-like kinase hKFC interact with the serine/threonine-rich region of gamma-2 herpesvirus replication and transcription activator (RTA) (PMID:14585985)
interaction of ADPRT and WRN resulting in ADP-ribosylation of the WRN protein; results imply that WRN is involved in DNA replication and in DNA repair (PMID:14596914)
the WRN/PARP-1 complex plays a key role in the cellular response to oxidative stress and alkylating agents, suggesting a role for these proteins in the base excision DNA repair pathway (PMID:14612404)
nitric oxide and reactive nitrogen oxide species inhibit PARP (PMID:14642390)
PARP-1 and PARP-2 act as positive regulators of genomic stability in eukaryotic cells by counteracting topoisomerase I-induced DNA damage (PMID:14699148)
activity of E. coli topoisomerase I is specifically associated with poly(ADP-ribose) polymerase-1 (PMID:14715657)
Data show that poly(ADP-ribose) polymerase 1 (PARP-1) is expressed during fetal development and undergoes complex developmental changes in expression, and that inhibition of PARP-1 activity differentially affects expression of surfactant proteins. (PMID:14754756)
PARP-immunoreactivity is increased in reactive astrocytes in the central nervous system of SOD1(G93A) transgenic mice, suggesting a role for PARP-expressing astrocytes in the pathogenesis and progress of amyotrophic lateral sclerosis. (PMID:15019581)
PARP-1 in biopsy specimens from aged donors may be a useful predictive factor for renal graft function. (PMID:15110646)
identify TIN2 as a PARP modulator in the TRF1 complex (PMID:15133513)
function for the automodification reaction is to regulate the interaction between PARP-1 and Topo I, and consequently, the Topo I activity, in response to DNA damage. (PMID:15247263)
Over-activation of PARP can contribute to the pathomechanism of the disease-specific lesion of the neurons in the substantia nigra in Parkinson disease. (PMID:15257133)
required for efficient HIV-1 replication in human cells (PMID:15280503)
Inhibition of PARP-1 and DNA-dependent protein kinase id a powerful strategy for tumor radiosensitization. (PMID:15286704)
Poly(ADP-ribose) polymerase 1 inactivates the catalytic activities of the Werner syndrome protein. (PMID:15292449)
ICAM-1, VCAM-1, E-selectin and interleukin-6 expression are enhanced by glucose and regulated by poly(ADP-ribose) polymerase in human umbilical endothelial cells (PMID:15304054)
PARP1 bound directly to a specific region within the Kaposi’s sarcoma-associated herpesvirus (KSHV) terminal repeat sequence (PMID:15331727)
role for PARP in the onset and progression of cardiac hypertrophy; some events related to cardiac hypertrophy growth and progression to heart failure are mediated by a PARP-dependent mechanism. (PMID:15374823)
Increased expression of poly(ADP-ribose) polymerase is associated with hepatocellular carcinoma (PMID:15375506)
Data provide novel insight into the function of poly(ADP-ribose) polymerase-1 (PARP-1) in inflammation and ischemia-related pathophysiologies. (PMID:15489954)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	parp1	ENSDARG00000019529
mus_musculus	Parp1	ENSMUSG00000026496
rattus_norvegicus	Parp1	ENSRNOG00000003084
drosophila_melanogaster	Parp1	FBGN0010247
caenorhabditis_elegans	parp-1	WBGENE00004049

Paralogs (2): PARP3 (ENSG00000041880), PARP2 (ENSG00000129484)

Protein

Protein identifiers

Poly [ADP-ribose] polymerase 1 — P09874 (reviewed: P09874)

Alternative names: ADP-ribosyltransferase diphtheria toxin-like 1, DNA ADP-ribosyltransferase PARP1, NAD(+) ADP-ribosyltransferase 1, Poly[ADP-ribose] synthase 1, Protein poly-ADP-ribosyltransferase PARP1

All UniProt accessions (5): P09874, A0A7I2V384, A0A7I2V3E1, A0A7I2V5E9, A0A7I2V625

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, serine, histidine or tyrosine 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. Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1. Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site. Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1. Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity. PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), 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 PARP1 in order to limit the length of poly-ADP-ribose chains. In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation. Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5. In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2’-OH group in single- and double-stranded DNA, respectively. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair. In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity. Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II. Acts both as a positive and negative regulator of transcription elongation, depending on the context. Acts as a positive regulator of transcription elongation by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding activity of NELFE and relieving transcription pausing. Acts as a negative regulator of transcription elongation in response to DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the phase separation activity of CCNT1 and subsequent activation of CDK9. Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression. Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos. Also acts as a negative regulator of the cGAS-STING pathway. Acts by mediating poly-ADP-ribosylation of CGAS: PARP1 translocates into the cytosol following phosphorylation by PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS. Acts as a negative regulator of adipogenesis: catalyzes poly-ADP-ribosylation of histone H2B on ‘Glu-35’ (H2BE35ADPr) following interaction with NMNAT1, inhibiting phosphorylation of H2B at ‘Ser-36’ (H2BS36ph), thereby blocking expression of pro-adipogenetic genes. Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming. Promotes AIFM1-mediated apoptosis. This form, which translocates into the cytoplasm following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, is auto-poly-ADP-ribosylated and serves as a poly-ADP-ribose carrier to induce AIFM1-mediated apoptosis. This cleavage form irreversibly binds to DNA breaks and interferes with DNA repair, promoting DNA damage-induced apoptosis.

Subunit / interactions. Homodimer; PARP-type zinc-fingers from separate PARP1 molecules form a dimer module that specifically recognizes DNA strand breaks. Heterodimer; heterodimerizes with PARP2. Interacts (via the PARP catalytic domain) with HPF1. Interacts with NMNAT1. Interacts with nucleosomes; with a preference for nucleosomes containing H2A.X. Interacts with APTX. Component of a base excision repair (BER) complex, containing at least XRCC1, PARP1, PARP2, POLB and LRIG3. Interacts with SRY. The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70. Interacts with TIAM2. Interacts with PARP3; leading to activate PARP1 in absence of DNA. Interacts (when poly-ADP-ribosylated) with CHD1L (via macro domain). Interacts with the DNA polymerase alpha catalytic subunit POLA1; this interaction functions as part of the control of replication fork progression. Interacts with EEF1A1 and TXK. Interacts with RNF4. Interacts with RNF146. Interacts with ZNF423. Interacts with APLF. Interacts with SNAI1 (via zinc fingers); the interaction requires SNAI1 to be poly-ADP-ribosylated and non-phosphorylated (active) by GSK3B. Interacts (when poly-ADP-ribosylated) with PARP9. Interacts with NR4A3; activates PARP1 by improving acetylation of PARP1 and suppressing the interaction between PARP1 and SIRT1. Interacts (via catalytic domain) with PUM3; the interaction inhibits the poly-ADP-ribosylation activity of PARP1 and the degradation of PARP1 by CASP3 following genotoxic stress. Interacts with ZNF365. Interacts with RRP1B. Interacts with TIMELESS; the interaction is direct. Interacts with CGAS; leading to impede the formation of the PARP1-TIMELESS complex. Interacts with KHDC3L, the interaction is increased following the formation of DNA double-strand breaks. Interacts (when auto-poly-ADP-ribosylated) with XRCC1; leading to inhibit PARP1 ADP-ribosyltransferase activity. Interacts with SPINDOC; promoting PARP1 ADP-ribosyltransferase activity. Interacts with BANF1; leading to inhibit PARP1 ADP-ribosyltransferase activity in response to oxidative DNA damage. Interacts (when sumoylated and ubiquitinated) with VCP/p97; leading to its extraction from chromatin. Interacts with YARS1; Interacts with PACMP micropeptide; interaction. Interacts with PACMP micropeptide; Interacts with PACMP micropeptide; interaction. Interacts (when poly-ADP-ribosylated) with isoform 1 of MACROH2A1; MACROH2A1 specifically binds to poly-ADP-ribose chains and inhibits PARP1 activity, limiting the consumption of nuclear NAD(+). Interacts with CARM1; promoting recruitment to replication forks. Interacts with RECQL. Interacts with ZNF32; the interaction reshapes ZNF432 interacting proteins. Interacts with TPRN; TPRN interacts with a number of DNA damage response proteins, is recruited to sites of DNA damage and may play a role in DNA damage repair. Interacts (when auto-poly-ADP-ribosylated) with AIFM1. (Microbial infection) Interacts with human herpesvirus 8 (KSHV) protein RTA/ORF50; this interaction negatively regulates RTA/ORF50 transactivation activity.

Subcellular location. Chromosome. Nucleus. Nucleolus. Cytoplasm. Cytosol Chromosome Cytoplasm.

Post-translational modifications. Poly-ADP-ribosylated on serine, glutamate and aspartate residues by autocatalysis. Auto-ADP-ribosylation on serine takes place following interaction with HPF1. Auto poly-ADP-ribosylation on serine residues promotes its dissociation from chromatin. Poly-ADP-ribosylated by PARP2; poly-ADP-ribosylation mediates the recruitment of CHD1L to DNA damage sites. Mono-ADP-ribosylated at Lys-521 by SIRT6 in response to oxidative stress, promoting recruitment to double-strand breaks (DSBs) sites. Phosphorylated at Thr-594 by PRKDC in response to DNA damage following virus infection, promoting its translocation to the cytosol. Phosphorylated by TXK. S-nitrosylated, leading to inhibit transcription regulation activity. Proteolytically cleaved by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis to generate the Poly [ADP-ribose] polymerase 1, processed N-terminus and Poly [ADP-ribose] polymerase 1, processed C-terminus forms. CASP3-mediated cleavage is promoted by the TP53/p53-induced long non-coding RNA SPARCLE, which binds PARP1 in response to genotoxic stress. Sumoylated with SUMO1 or SUMO2 by PIAS4 following prolonged residence (trapping) to chromatin. Sumoylation promotes ubiquitination by RNF4 and removal from chromatin by VCP/p97. Ubiquitinated by RNF4 following sumoylation by PIAS4 in response to prolonged residence (trapping) to chromatin. Ubiquitination promotes removal from chromatin by VCP/p97.

Activity regulation. ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism. In absence of activation signal, PARP1 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding. Activity is highly stimulated by signals, such as DNA strand breaks. Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition. Poly-ADP-ribosyltransferase activity is tightly regulated and PARP1 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences. A number of factors (VCP/p97) or post-translational modifications (auto-poly-ADP-ribosylation or ubiquitination) promote PARP1 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 can be classified in three categories: type I compounds (EB-47, UKTT15 and BAD) that promote allosteric retention of PARP1 on DNA, type II inhibitors (talazoparib and olaparib) that mediate a non-allosteric inhibition, and type III inhibitors (rucaparib, niraparib, and veliparib) that promote allosteric release from DNA. Trapping to chromatin by PARPi molecules triggers activation of the cGAS-STING pathway.

Domain organisation. The two PARP-type zinc-fingers (also named Zn1 and Zn2) specifically recognize DNA strand breaks: PARP-type zinc-finger 1 binds PARP-type zinc-finger 2 from a separate PARP1 molecule to form a dimeric module that specifically recognizes DNA strand breaks. The PADR1-type (also named Zn3) zinc-finger mediates an interdomain contact and is required for the ability of PARP1 to regulate chromatin structure. The BRCT domain is able to bind intact DNA without activating the poly-ADP-ribosyltransferase activity. The BRCT domain mediates DNA intrastrand transfer (named ‘monkey-bar mechanism’) that allows rapid movements of PARP1 through the nucleus. The WGR domain bridges two nucleosomes, with the broken DNA aligned in a position suitable for ligation. The bridging induces structural changes in PARP1 that signal the recognition of a DNA break to the catalytic domain of PARP1, promoting HPF1 recruitment and subsequent activation of PARP1, 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.

RefSeq proteins (1): NP_001609* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001357	BRCT_dom	Domain
IPR001510	Znf_PARP	Domain
IPR004102	Poly(ADP-ribose)pol_reg_dom	Domain
IPR008288	PARP	Family
IPR008893	WGR_domain	Domain
IPR012317	Poly(ADP-ribose)pol_cat_dom	Domain
IPR012982	PARP1-like_PADR1_Zn_ribbon	Domain
IPR036420	BRCT_dom_sf	Homologous_superfamily
IPR036616	Poly(ADP-ribose)pol_reg_dom_sf	Homologous_superfamily
IPR036930	WGR_dom_sf	Homologous_superfamily
IPR036957	Znf_PARP_sf	Homologous_superfamily
IPR038650	PADR1_C_dom_sf	Homologous_superfamily
IPR049296	PARP1-like_PADR1_N	Domain
IPR050800	ARTD/PARP	Family

Pfam: PF00533, PF00644, PF00645, PF02877, PF05406, PF08063, PF21728

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), 5 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)
L-tyrosyl-[protein] + NAD(+) = O-(ADP-D-ribosyl)-L-tyrosyl-[protein] + nicotinamide + H(+) (RHEA:58236)
L-histidyl-[protein] + NAD(+) = N(tele)-(ADP-D-ribosyl)-L-histidyl-[protein] + nicotinamide + H(+) (RHEA:72071)

UniProt features (282 total): mutagenesis site 82, strand 49, helix 39, modified residue 38, binding site 16, turn 12, cross-link 11, sequence variant 8, sequence conflict 7, domain 5, region of interest 4, chain 3, zinc finger region 2, short sequence motif 2, initiator methionine 1, compositionally biased region 1, active site 1, site 1

Structure

Experimental structures (PDB)

106 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6NRH	X-RAY DIFFRACTION	1.5
9ETQ	X-RAY DIFFRACTION	1.59
7AAC	X-RAY DIFFRACTION	1.59
6NRJ	X-RAY DIFFRACTION	1.65
7KK2	X-RAY DIFFRACTION	1.7
2RIQ	X-RAY DIFFRACTION	1.7
6NRG	X-RAY DIFFRACTION	1.7
7KK5	X-RAY DIFFRACTION	1.7
7AAA	X-RAY DIFFRACTION	1.74
6NTU	X-RAY DIFFRACTION	1.8
9ETR	X-RAY DIFFRACTION	1.82
7ONT	X-RAY DIFFRACTION	1.85
4ZZZ	X-RAY DIFFRACTION	1.9
5WS1	X-RAY DIFFRACTION	1.9
7KK4	X-RAY DIFFRACTION	1.96
7ONS	X-RAY DIFFRACTION	1.97
6M3I	X-RAY DIFFRACTION	1.98
6NRF	X-RAY DIFFRACTION	2
6XVW	X-RAY DIFFRACTION	2
7ONR	X-RAY DIFFRACTION	2.05
8VYH	X-RAY DIFFRACTION	2.05
7KK3	X-RAY DIFFRACTION	2.06
7KK6	X-RAY DIFFRACTION	2.06
4XHU	X-RAY DIFFRACTION	2.09
6VKK	X-RAY DIFFRACTION	2.1
8HE7	X-RAY DIFFRACTION	2.1
9CKC	X-RAY DIFFRACTION	2.1
4L6S	X-RAY DIFFRACTION	2.2
4R6E	X-RAY DIFFRACTION	2.2
4UND	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09874-F1	83.23	0.51

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): 988 (for poly [adp-ribose] polymerase activity); 214–215 (cleavage; by caspase-3 and caspase-7)

Ligand- & substrate-binding residues (16): 21; 24; 53; 56; 125; 128; 159; 162; 295; 298; 311; 321 …

Post-translational modifications (49): 2, 41, 97, 105, 131, 177, 179, 185, 274, 277, 364, 368, 387, 407, 413, 435, 437, 444, 445, 448 …

Mutagenesis-validated functional residues (82):

Position	Phenotype
43	no effect.
43	strongly decreased homodimerization.
44–48	abolished dna-binding.
44	abolished dna-binding.
44	strongly decreased homodimerization.
45	does not affect dna-binding. decreased poly-adp-ribosyltransferase activity.
119–120	abolished prolonged residence (trapping) to chromatin.
122	strongly decreased dna-binding.
138	abolished binding to dna strand breaks.
151–154	abolished dna-binding.
214	abolished cleavage by caspase-7 (casp7).
241	does not affect auto-poly-adp-ribosylation.
246	decreased poly-adp-ribosyltransferase activity upon binding to damaged dna.
298	decreased stability leading to impaired oly-adp-ribosyltransferase activity.
314	does not affect auto-poly-adp-ribosylation.
315	does not affect auto-poly-adp-ribosylation.
316	strongly reduced poly-adp-ribosyltransferase and ability to regulate chromatin compaction.
317	does not affect auto-poly-adp-ribosylation.
318	strongly reduced poly-adp-ribosyltransferase activity. able to bind damaged dna, however, defects in the interdomain com
318	does not affect auto-poly-adp-ribosylation.
319	does not affect auto-poly-adp-ribosylation.
320	does not affect auto-poly-adp-ribosylation.
325	does not affect translocation into the cytosol.
348–350	does not affect auto-poly-adp-ribosylation.
357	does not affect auto-poly-adp-ribosylation.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-110362	POLB-Dependent Long Patch Base Excision Repair
R-HSA-192814	vRNA Synthesis
R-HSA-2173795	Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
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: 607 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_CIRCADIAN_RHYTHM, REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_CHROMOSOME_ORGANIZATION, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_RESPONSE_TO_ETHANOL, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_RESPONSE_TO_ZINC_ION

GO Biological Process (64): negative regulation of transcription by RNA polymerase II (GO:0000122), telomere maintenance (GO:0000723), DNA repair (GO:0006281), double-strand break repair (GO:0006302), transcription by RNA polymerase II (GO:0006366), apoptotic process (GO:0006915), DNA damage response (GO:0006974), mitochondrion organization (GO:0007005), transforming growth factor beta receptor signaling pathway (GO:0007179), response to gamma radiation (GO:0010332), positive regulation of cardiac muscle hypertrophy (GO:0010613), carbohydrate biosynthetic process (GO:0016051), protein autoprocessing (GO:0016540), signal transduction involved in regulation of gene expression (GO:0023019), macrophage differentiation (GO:0030225), DNA ADP-ribosylation (GO:0030592), mitochondrial DNA metabolic process (GO:0032042), positive regulation of DNA-templated transcription, elongation (GO:0032786), cellular response to insulin stimulus (GO:0032869), regulation of protein localization (GO:0032880), positive regulation of intracellular estrogen receptor signaling pathway (GO:0033148), negative regulation of transcription elongation by RNA polymerase II (GO:0034244), cellular response to oxidative stress (GO:0034599), cellular response to UV (GO:0034644), protein modification process (GO:0036211), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), mitochondrial DNA repair (GO:0043504), innate immune response (GO:0045087), regulation of circadian sleep/wake cycle, non-REM sleep (GO:0045188), response to ethanol (GO:0045471), negative regulation of innate immune response (GO:0045824), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), decidualization (GO:0046697), positive regulation of mitochondrial depolarization (GO:0051901), positive regulation of SMAD protein signal transduction (GO:0060391), positive regulation of necroptotic process (GO:0060545), protein poly-ADP-ribosylation (GO:0070212), protein auto-ADP-ribosylation (GO:0070213), protein localization to chromatin (GO:0071168)

GO Molecular Function (35): DNA binding (GO:0003677), chromatin binding (GO:0003682), damaged DNA binding (GO:0003684), RNA binding (GO:0003723), NAD+ poly-ADP-ribosyltransferase activity (GO:0003950), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), nucleotidyltransferase activity (GO:0016779), enzyme binding (GO:0019899), protein kinase binding (GO:0019901), nuclear estrogen receptor binding (GO:0030331), nucleosome binding (GO:0031491), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), histone deacetylase binding (GO:0042826), NAD binding (GO:0051287), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), R-SMAD binding (GO:0070412), NAD DNA ADP-ribosyltransferase activity (GO:0140294), transcription regulator activator activity (GO:0140537), NAD+-protein-serine ADP-ribosyltransferase activity (GO:0140805), NAD+-protein-aspartate ADP-ribosyltransferase activity (GO:0140806), NAD+-protein-glutamate ADP-ribosyltransferase activity (GO:0140807), NAD+-protein-tyrosine ADP-ribosyltransferase activity (GO:0140808), NAD+-protein-histidine ADP-ribosyltransferase activity (GO:0140815), NAD+-histone H2BS6 serine ADP-ribosyltransferase activity (GO:0140816), NAD+-histone H3S10 serine ADP-ribosyltransferase activity (GO:0140817), NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity (GO:0140822), NAD+-protein mono-ADP-ribosyltransferase activity (GO:1990404), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), metal ion binding (GO:0046872)

GO Cellular Component (18): chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), nucleolus (GO:0005730), mitochondrion (GO:0005739), cytosol (GO:0005829), membrane (GO:0016020), nuclear body (GO:0016604), protein-containing complex (GO:0032991), protein-DNA complex (GO:0032993), site of double-strand break (GO:0035861), nuclear replication fork (GO:0043596), site of DNA damage (GO:0090734), chromosome (GO:0005694), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	3
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1
Influenza Viral RNA Transcription and Replication	1
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
SUMO E3 ligases SUMOylate target proteins	1
Homology Directed Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
DNA metabolic process	3
intracellular membraneless organelle	3
nucleic acid binding	2
pentosyltransferase activity	2
protein binding	2
chromosome	2
intracellular membrane-bounded organelle	2
nucleus	2
nuclear lumen	2
protein-containing complex	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
telomere organization	1
DNA damage response	1
DNA repair	1
DNA-templated transcription	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
organelle organization	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
response to ionizing radiation	1
cardiac muscle hypertrophy	1
regulation of cardiac muscle hypertrophy	1
positive regulation of muscle hypertrophy	1
carbohydrate metabolic process	1
biosynthetic process	1
protein processing	1
signal transduction	1
regulation of gene expression	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
DNA modification	1
mitochondrion	1
DNA-templated transcription elongation	1

Protein interactions and networks

STRING

5700 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARP1	XRCC1	P18887	996
PARP1	SMARCA4	P51532	995
PARP1	XRCC6	P12956	983
PARP1	PRKDC	P78527	976
PARP1	LIG3	P49916	973
PARP1	XRCC5	P13010	968
PARP1	POLB	P06746	963
PARP1	CASP3	P42574	954
PARP1	NPM1	P06748	950
PARP1	BRCA2	P51587	942
PARP1	PARG	Q86W56	940
PARP1	BRCA1	P38398	936
PARP1	CASP9	P55211	916
PARP1	APEX1	P27695	912
PARP1	ZC3HAV1	Q7Z2W4	894

IntAct

541 interactions, top by confidence:

A	B	Type	Score
APLF	PARP1	psi-mi:“MI:0915”(physical association)	0.870
APLF	PARP1	psi-mi:“MI:0407”(direct interaction)	0.870
APLF	PARP1	psi-mi:“MI:0914”(association)	0.870
PARP1	XRCC6	psi-mi:“MI:0914”(association)	0.850
XRCC6	PARP1	psi-mi:“MI:0914”(association)	0.850
PARP1	H2AX	psi-mi:“MI:0403”(colocalization)	0.840
H2AX	PARP1	psi-mi:“MI:0914”(association)	0.840
RARA	NCOR1	psi-mi:“MI:0914”(association)	0.800
RNF146	TNKS	psi-mi:“MI:0914”(association)	0.790
H3C1	HAT1	psi-mi:“MI:0914”(association)	0.770
APTX	PARP1	psi-mi:“MI:0915”(physical association)	0.770
PARP1	TP53	psi-mi:“MI:0407”(direct interaction)	0.750
RECQL	PARP1	psi-mi:“MI:0407”(direct interaction)	0.750
RECQL	PARP1	psi-mi:“MI:0915”(physical association)	0.750
RECQL	PARP1	psi-mi:“MI:0914”(association)	0.750
PARP1	RECQL	psi-mi:“MI:0557”(adp ribosylation reaction)	0.750
PARP1	TP53	psi-mi:“MI:0914”(association)	0.750
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730

BioGRID (2129): PARP1 (Biochemical Activity), PARP1 (Biochemical Activity), PARP1 (Affinity Capture-MS), PARP1 (Affinity Capture-MS), PARP1 (Biochemical Activity), PARP1 (Affinity Capture-Western), PARP1 (Biochemical Activity), PARP1 (Reconstituted Complex), PARP1 (Affinity Capture-RNA), PARP1 (Affinity Capture-RNA), PARP1 (Affinity Capture-RNA), PARP1 (Biochemical Activity), HIST1H4A (Biochemical Activity), PARP1 (Biochemical Activity), PARP1 (Biochemical Activity)

ESM2 similar proteins: A0A075QQ08, A0A1D8EJF9, A0A1U8F5V2, A0A1U8GR65, A0A2J6L8Y7, A0A3Q7FGP1, A0A3Q7I7R4, A0A445AGS0, A7KWF8, C6ZJZ3, C7SG33, D3UW26, K0P2S0, M1J8U6, M1JJT8, O04663, O23252, O60573, O61955, O77210, O81481, O81482, P07260, P09874, P0DXI0, P0DXI5, P26446, P29557, P48598, P48599, P48600, P78954, Q03389, Q0GRC4, Q22888, Q3UTA9, Q4QXS7, Q4VQY1, Q4VQY3, Q5RHR0

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, A0A7H0DNE6, A1RY72, A8AB20, A8MDU6, B1L3V2, B1YA52, C0QSL7, C3MJ14, C3MYD2, C3MZR1, C3N834, C3NF77, C4KIZ2

SIGNOR signaling

44 interactions.

A	Effect	B	Mechanism
MAPK1	up-regulates	PARP1	phosphorylation
veliparib	down-regulates	PARP1	“chemical inhibition”
LSM-1988	down-regulates	PARP1	“chemical inhibition”
4-Iodo-3-nitrobenzamide	down-regulates	PARP1	“chemical inhibition”
1038915-60-4	down-regulates	PARP1	“chemical inhibition”
olaparib	down-regulates	PARP1	“chemical inhibition”
A-966492	down-regulates	PARP1	“chemical inhibition”
ERK1/2	up-regulates	PARP1	phosphorylation
PARP1	“form complex”	SNAIL/RELA/PARP1	binding
PARP1	“down-regulates quantity by repression”	SERPINF1	“transcriptional regulation”
PARP1	“up-regulates quantity by expression”	THBD	“transcriptional regulation”
PARP1	“down-regulates quantity by repression”	THBD	“transcriptional regulation”
“Caspase 7 complex”	down-regulates	PARP1	cleavage
DNA_damage	up-regulates	PARP1
PARP1	“up-regulates activity”	POLA1	binding
PARP1	“up-regulates activity”	TP53	relocalization
PARP1	“up-regulates quantity”	CHD2	binding
CHFR	“down-regulates quantity by destabilization”	PARP1	polyubiquitination
PARP1	“up-regulates activity”	KDM5B	relocalization
ZNF365	“up-regulates activity”	PARP1	binding
PARP1	“up-regulates activity”	MRE11	relocalization
NAT10	“up-regulates quantity by stabilization”	PARP1	acetylation
PRKACA	“up-regulates activity”	PARP1	phosphorylation
ATR	“down-regulates activity”	PARP1	phosphorylation
ATR	down-regulates	PARP1	phosphorylation
PHRF1	“down-regulates quantity by destabilization”	PARP1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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
Nuclear events stimulated by ALK signaling in cancer	6	18.3×	1e-04
PTEN Regulation	6	12.8×	3e-04
DNA methylation	7	11.7×	2e-04
Nonhomologous End-Joining (NHEJ)	7	11.0×	3e-04
Pre-NOTCH Transcription and Translation	9	10.3×	4e-05
RNA Polymerase I Promoter Opening	6	10.3×	1e-03
Defective pyroptosis	7	10.2×	3e-04
B-WICH complex positively regulates rRNA expression	9	10.2×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair via nonhomologous end joining	8	25.1×	5e-07
activation of innate immune response	5	18.0×	1e-03
nucleotide-excision repair	6	17.1×	2e-04
double-strand break repair	10	15.2×	5e-07
mRNA stabilization	5	13.7×	2e-03
heterochromatin formation	6	11.4×	2e-03
nucleosome assembly	10	10.5×	1e-05
telomere maintenance	5	10.0×	7e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	13
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

3166 predictions. Top by Δscore:

Variant	Effect	Δscore
1:226364996:ACAT:A	donor_loss	1.0000
1:226364998:ATACC:A	donor_loss	1.0000
1:226364999:TACCA:T	donor_loss	1.0000
1:226365000:A:AC	donor_gain	1.0000
1:226365000:A:T	donor_loss	1.0000
1:226365001:C:CA	donor_loss	1.0000
1:226365001:C:CC	donor_gain	1.0000
1:226365001:CCA:C	donor_gain	1.0000
1:226365152:GAT:G	acceptor_gain	1.0000
1:226365159:T:TC	acceptor_gain	1.0000
1:226365164:G:C	acceptor_gain	1.0000
1:226365164:G:GC	acceptor_gain	1.0000
1:226365167:G:C	acceptor_gain	1.0000
1:226365167:G:GC	acceptor_gain	1.0000
1:226365172:C:CT	acceptor_gain	1.0000
1:226365173:A:T	acceptor_gain	1.0000
1:226365948:TCTTA:T	donor_loss	1.0000
1:226365949:CTTA:C	donor_loss	1.0000
1:226365950:TTAC:T	donor_loss	1.0000
1:226365951:TA:T	donor_loss	1.0000
1:226365952:A:AC	donor_gain	1.0000
1:226365953:C:CT	donor_gain	1.0000
1:226365953:CA:C	donor_gain	1.0000
1:226365953:CAT:C	donor_gain	1.0000
1:226365953:CATCG:C	donor_gain	1.0000
1:226365964:T:TA	donor_gain	1.0000
1:226366048:ACCAC:A	acceptor_gain	1.0000
1:226366049:CCAC:C	acceptor_gain	1.0000
1:226366049:CCACC:C	acceptor_gain	1.0000
1:226366050:CAC:C	acceptor_gain	1.0000

AlphaMissense

6722 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:226361969:T:A	E988V	1.000
1:226362077:C:T	G952D	1.000
1:226363106:A:C	S947R	1.000
1:226363106:A:T	S947R	1.000
1:226363108:T:G	S947R	1.000
1:226364005:G:C	C908W	1.000
1:226364015:G:T	A905D	1.000
1:226364017:A:C	S904R	1.000
1:226364017:A:T	S904R	1.000
1:226364019:T:G	S904R	1.000
1:226364020:C:A	K903N	1.000
1:226364020:C:G	K903N	1.000
1:226364024:G:A	S902F	1.000
1:226364048:C:T	G894E	1.000
1:226364049:C:A	G894W	1.000
1:226364049:C:G	G894R	1.000
1:226364049:C:T	G894R	1.000
1:226364054:C:A	G892V	1.000
1:226364056:A:C	F891L	1.000
1:226364056:A:T	F891L	1.000
1:226364058:A:G	F891L	1.000
1:226365021:G:T	A880D	1.000
1:226365048:C:T	G871E	1.000
1:226365056:G:C	N868K	1.000
1:226365056:G:T	N868K	1.000
1:226365072:C:T	G863E	1.000
1:226365073:C:A	G863W	1.000
1:226365079:A:G	W861R	1.000
1:226365079:A:T	W861R	1.000
1:226367583:A:G	L768P	1.000

dbSNP variants (sampled 300 via entrez): RS1000032633 (1:226402145 T>C), RS1000033 (1:226392686 T>G), RS1000045025 (1:226400184 C>G,T), RS1000106754 (1:226409711 T>G), RS1000151354 (1:226394504 G>C), RS1000201264 (1:226410000 T>C), RS1000226311 (1:226388789 A>C,G), RS1000228171 (1:226371216 G>A), RS1000264664 (1:226405901 A>C,G), RS1000277161 (1:226388581 G>A,C,T), RS1000285148 (1:226399194 T>C), RS1000291293 (1:226365415 ATCTATGT>A), RS1000403073 (1:226365664 G>A), RS1000424008 (1:226399410 A>C), RS1000468074 (1:226360622 T>C)

Disease associations

OMIM: gene MIM:173870 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (2): hereditary renal cell carcinoma (MONDO:0003008), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001266_2	Melanoma	9.000000e-08
GCST005143_1	Telomere length	2.000000e-06
GCST005194_192	Coronary artery disease	7.000000e-06
GCST005991_6	Platelet count	2.000000e-08
GCST007505_16	Nevus count or cutaneous melanoma	1.000000e-11
GCST008366_15	Leukocyte telomere length	2.000000e-18
GCST008366_5	Leukocyte telomere length	2.000000e-16
GCST008394_1	Mild to moderate chronic kidney disease	1.000000e-06
GCST009856_1	Leukocyte telomere length	1.000000e-10
GCST010303_20	Nevus count or cutaneous melanoma	2.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004632	nevus count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C536851	Familial renal cell carcinoma (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL3105 (SINGLE PROTEIN), CHEMBL3390820 (PROTEIN FAMILY), CHEMBL4742271 (PROTEIN-PROTEIN INTERACTION), CHEMBL4748223 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

24 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 225,530 (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
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL3137320	TALAZOPARIB	4	5,534
CHEMBL3833368	RUCAPARIB CAMSYLATE	4	1,998
CHEMBL521686	OLAPARIB	4	13,038
CHEMBL629	AMITRIPTYLINE	4	52,595
CHEMBL1170047	INIPARIB	3	3,007
CHEMBL3930624	FLUZOPARIB	3	594
CHEMBL4112930	PAMIPARIB	3	2,114
CHEMBL506871	VELIPARIB	3	5,421
CHEMBL5095220	SARUPARIB	3	357
CHEMBL124815	CHLORTHENOXAZINE	2	1,082
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL275638	FLAVONE	2	88,985
CHEMBL3527000	E-7016	2	194
CHEMBL3644587	2X-121	2	248
CHEMBL3649803	AMELPARIB	2	55
CHEMBL5095245	NESUPARIB	2	100
CHEMBL2105733	RUCAPARIB PHOSPHATE	1	141
CHEMBL4098253	AZD2461	1
CHEMBL4297461	CEP-9722	1
CHEMBL5095043	ATAMPARIB	1
CHEMBL5095223	AZD-9574	1

Clinical evidence (CIViC)

Drug × variant × indication: 3 predictive associations from 3 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
PARP1 OVEREXPRESSION	Olaparib	Malignant Peripheral Nerve Sheath Tumor	Sensitivity/Response	CIViC D	EID7016
PARP1 OVEREXPRESSION	Trabectedin + Olaparib	Sarcoma	Sensitivity/Response	CIViC D	EID7868
PARP1 OVEREXPRESSION	Olaparib	Breast Cancer	Resistance	CIViC D	EID7867

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 (20 total), top 20:

Ligand	Action	Affinity	Parameter
PARP1 inhibitor (S)-G9	Inhibition	9.72	pIC50
pamiparib	Inhibition	8.89	pIC50
rucaparib	Inhibition	8.85	pKi
lerzeparib	Inhibition	8.55	pIC50
niraparib	Inhibition	8.42	pIC50
saruparib	Inhibition	8.4	pIC50
venadaparib	Inhibition	8.3	pIC50
palacaparib	Inhibition	8.3	pIC50
olaparib	Inhibition	8.3	pIC50
AG14361	Inhibition	8.24	pKi
fluzoparib	Inhibition	8.05	pIC50
KU0058948	Inhibition	7.72	pKd
PJ34	Inhibition	7.7	pIC50
dual VEGFR/PARP inhibitor 14b	Inhibition	7.22	pIC50
compound 10b [PMID: 26222319]	Inhibition	7.06	pKd
compound 5 [Tomassi et al., 2020]	Inhibition	7.05	pIC50
MC2050	Inhibition	6.92	pIC50
ciclopirox	Inhibition	6.8	pIC50
AZ1366	Inhibition	6.25	pIC50
ME0328	Inhibition	5.2	pIC50

Binding affinities (BindingDB)

1947 measured of 2386 human assays (2386 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-(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
BDBM214427	KI	0.1 nM	US-9283222: Inhibitors of poly(ADP-ribose)polymerase
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
US20250215013, Example 113	IC50	0.13 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE 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
US20250215013, Example 196	IC50	0.15 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 197	IC50	0.15 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE 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
US20250215013, Example 199	IC50	0.16 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE 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
4-(2-aminoethoxy)-3-(4-chloro-3-methylphenyl)-7-fluoro-3,4,4a,5,6,7,8,8a-octahydro-2H-isoquinolin-1-one	IC50	0.2 nM	US-9422243: 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors
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
US20250215013, Example 166	IC50	0.21 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE 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
US20250215013, Example 144	IC50	0.23 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 181	IC50	0.23 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 180	IC50	0.24 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 185	IC50	0.24 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 53	IC50	0.25 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 112	IC50	0.26 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 165	IC50	0.26 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 178	IC50	0.28 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 183	IC50	0.28 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE 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
4-[[4-fluoro-3-(4-methyl-3-oxopiperazine-1-carbonyl)phenyl]methyl]-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-1-one	KI	0.3 nM	US-9283222: Inhibitors of poly(ADP-ribose)polymerase
N-methyl-5-[(1S,6R)-5-((6-oxo-5H,7H,8H,9H-cyclopenta[c][1,5]naphthyridin-3-yl)methyl)-2,5-diazabicyclo[4.2.0]octan-2-yl]pyridine-2-carboxamide and N-methyl-5-[(1R,6S)-5-((6-oxo-5H,7H,8H,9H-cyclopenta[c][1,5]naphthyridin-3-yl)methyl)-2,5-diazabicyclo[4.2.0]octan-2-yl]pyridine-2-carboxamide	IC50	0.3 nM	US-20250221987: PIPERAZINO RING-CONTAINING DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
US20250221987, Example 16-2	IC50	0.3 nM	US-20250221987: PIPERAZINO RING-CONTAINING DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
N-methyl-5-((1S,6R)-5-((6-oxo-6,8,9,10-tetrahydro-5H-pyrano[2,3-c][1,5]naphthyridin-3-yl)methyl)-2,5-diazabicyclo[4.2.0]octan-2-yl)picolinamide and N-methyl-5-((1R,6S)-5-((6-oxo-6,8,9,10-tetrahydro-5H-pyrano[2,3-c][1,5]naphthyridin-3-yl)methyl)-2,5-diazabicyclo[4.2.0]octan-2-yl)picolinamide	IC50	0.3 nM	US-20250221987: PIPERAZINO RING-CONTAINING DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
US20250221987, Example 46-2	IC50	0.3 nM	US-20250221987: PIPERAZINO RING-CONTAINING DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
US20250215013, Example 177	IC50	0.32 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 182	IC50	0.32 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
N-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)-5-(4-((7-ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl)piperazin-1-yl)picolinamide	IC50	0.32 nM	US-20250222116: PARP-1 DEGRADATION AGENT AND USE 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
US20250215013, Example 167	IC50	0.33 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE 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
US20250215013, Example 43	IC50	0.39 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
8-[[4-fluoro-3-(4-pyrazin-2-ylpiperazine-1-carbonyl)phenyl]methyl]-2,3,4,6-tetrahydro-1H-pyrido[2,3-d]pyridazin-5-one	KI	0.4 nM	US-9283222: Inhibitors of poly(ADP-ribose)polymerase
N-cyclopropyl-5-((1S,6R)-5-((7-ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl)-2,5-diazabicyclo[4.2.0]octan-2-yl)picolinamide and N-cyclopropyl-5-((1R,6S)-5-((7-ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl)-2,5-diazabicyclo[4.2.0]octan-2-yl)picolinamide	IC50	0.4 nM	US-20250221987: PIPERAZINO RING-CONTAINING DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
4-(4-(3-(8-fluoro-1-oxo-1,2- dihydroisoquinolin-3- yl)propyl)piperazin-1- yl)benzonitrile hydrochloride	IC50	0.41 nM	US-12459899: Isoquinolinone derivatives, method for preparing the same, and pharmaceutical composition for preventing or treating poly(ADP-ribose) polymerase-1-related diseases, comprising the same as active ingredient
US20250215013, Example 59	IC50	0.43 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 131	IC50	0.45 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE 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

ChEMBL bioactivities

5805 potent at pChembl≥5 of 6030 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL4169012
10.70	IC50	0.02	nM	CHEMBL5401127
10.66	IC50	0.022	nM	CHEMBL5575335
10.64	IC50	0.023	nM	CHEMBL5396891
10.21	IC50	0.061	nM	VELIPARIB
10.00	Ki	0.1	nM	CHEMBL3889630
10.00	IC50	0.1	nM	CHEMBL4170665
10.00	IC50	0.1	nM	OLAPARIB
9.92	IC50	0.12	nM	CHEMBL5562332
9.77	IC50	0.17	nM	CHEMBL5425729
9.77	IC50	0.17	nM	CHEMBL6146942
9.76	IC50	0.175	nM	CHEMBL5403789
9.72	IC50	0.19	nM	CHEMBL4845834
9.72	IC50	0.19	nM	CHEMBL5417456
9.70	IC50	0.2	nM	CHEMBL3933136
9.70	IC50	0.2	nM	CHEMBL4159834
9.70	EC50	0.2	nM	PAMIPARIB
9.70	IC50	0.2	nM	AMENTOFLAVONE
9.70	IC50	0.2	nM	CHEMBL3907010
9.70	IC50	0.2	nM	CHEMBL6159519
9.64	IC50	0.23	nM	CHEMBL4867855
9.64	IC50	0.23	nM	CHEMBL5404605
9.64	IC50	0.23	nM	CHEMBL6141678
9.62	Kd	0.24	nM	OLAPARIB
9.62	IC50	0.24	nM	CHEMBL5428376
9.62	IC50	0.24	nM	CHEMBL6141851
9.60	IC50	0.25	nM	CHEMBL5176874
9.60	IC50	0.25	nM	CHEMBL5416841
9.59	IC50	0.26	nM	CHEMBL5425393
9.55	IC50	0.28	nM	CHEMBL6149121
9.55	IC50	0.28	nM	CHEMBL6149501
9.52	Ki	0.3	nM	CHEMBL3958202
9.51	IC50	0.31	nM	CHEMBL2322618
9.51	Kd	0.31	nM	OLAPARIB
9.51	IC50	0.31	nM	SARUPARIB
9.49	IC50	0.32	nM	CHEMBL6168775
9.47	IC50	0.34	nM	CHEMBL5180001
9.43	Ki	0.376	nM	CHEMBL493045
9.40	Ki	0.4	nM	CHEMBL2058927
9.40	Ki	0.4	nM	CHEMBL2058928
9.40	IC50	0.4	nM	CHEMBL4169337
9.40	IC50	0.4	nM	CHEMBL4171279
9.40	IC50	0.4	nM	CHEMBL4800042
9.40	EC50	0.4	nM	OLAPARIB
9.40	IC50	0.4	nM	CHEMBL4870329
9.40	IC50	0.4	nM	CHEMBL5206717
9.40	IC50	0.4	nM	CHEMBL5420649
9.40	IC50	0.4	nM	OLAPARIB
9.39	IC50	0.41	nM	CHEMBL5182785
9.39	IC50	0.41	nM	CHEMBL5176160

PubChem BioAssay actives

2656 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[4-[2,3-difluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]benzonitrile	1499315: Inhibition of PARP1 (unknown origin) by ELISA	ic50	<0.0001	uM
2-[4-[4-(5-bromofuran-2-carbonyl)piperazine-1-carbonyl]phenyl]-1H-benzimidazole-4-carboxamide	2008605: Inhibition of PARP1 (unknown origin)	ic50	<0.0001	uM
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	2012683: Inhibition of PARP1 (unknown origin) using histone as substrate by ELISA	ic50	<0.0001	uM
4-[[4-fluoro-3-[3-[5-(thiomorpholin-4-ylmethyl)furan-2-yl]-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	2012683: Inhibition of PARP1 (unknown origin) using histone as substrate by ELISA	ic50	<0.0001	uM
4-[[3-[3-(4,5-dimethylfuran-2-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one	2012683: Inhibition of PARP1 (unknown origin) using histone as substrate by ELISA	ic50	<0.0001	uM
2-[4-[[4-[(2-aminophenyl)carbamoyl]phenyl]methylamino]phenyl]-1H-benzimidazole-4-carboxamide	2108843: Inhibition of PARP1 (unknown origin) using histone/NAD+ as substrates by NAD/NADH-Glo assay	ic50	<0.0001	uM
2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide	2008605: Inhibition of PARP1 (unknown origin)	ic50	0.0001	uM
4-[[3,4-difluoro-5-(4-pyridin-2-ylpiperazine-1-carbonyl)phenyl]methyl]-2H-phthalazin-1-one	1499315: Inhibition of PARP1 (unknown origin) by ELISA	ic50	0.0001	uM
4-[[3,4-difluoro-5-[4-(4-methylphenyl)piperazine-1-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	1499315: Inhibition of PARP1 (unknown origin) by ELISA	ic50	0.0001	uM
4-[[3-[3-(4-bromo-5-chlorofuran-2-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one	2012683: Inhibition of PARP1 (unknown origin) using histone as substrate by ELISA	ic50	0.0001	uM
4-[[4-fluoro-3-[4-[4-[2-[3-(1-methylpyrazol-4-yl)-6-oxopyridazin-1-yl]ethoxy]quinolin-7-yl]piperazine-1-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	2081676: Inhibition of PARP1 (unknown origin) using histone as substrate incubated for 45 mins by absorbance based analysis	ic50	0.0001	uM
Olaparib	2108843: Inhibition of PARP1 (unknown origin) using histone/NAD+ as substrates by NAD/NADH-Glo assay	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	1683888: Inhibition of PARP-1 in human HeLa cells incubated for 18 hrs in presence of H2O2	ec50	0.0002	uM
4-[[3,4-difluoro-5-[4-(1,3-thiazol-2-yl)piperazine-1-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	1499315: Inhibition of PARP1 (unknown origin) by ELISA	ic50	0.0002	uM
4-[[3-[4-(1H-benzimidazol-2-yl)piperazine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one	1764044: Inhibition of PARP1 (unknown origin)	ic50	0.0002	uM
2-[1-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperidin-4-yl]-3H-imidazo[4,5-c]pyridine-7-carboxamide	1764044: Inhibition of PARP1 (unknown origin)	ic50	0.0002	uM
4-[[4-fluoro-3-[3-(5-methylfuran-2-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	2012683: Inhibition of PARP1 (unknown origin) using histone as substrate by ELISA	ic50	0.0002	uM
5-[7-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-3-yl]furan-2-carbonitrile	2012683: Inhibition of PARP1 (unknown origin) using histone as substrate by ELISA	ic50	0.0002	uM
4-[[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-4-fluorophenyl]methyl]-5-hydroxy-2H-phthalazin-1-one	1976940: Inhibition of C-terminal His-tagged human recombinant PARP-1 (1 to 1014 residues) expressed in Sf9 insect cells incubated for 1 hr by 32P-NAD+-based filter binding assay	ic50	0.0002	uM
4-[[4-fluoro-3-[3-[5-(piperidin-1-ylmethyl)furan-2-yl]-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	2012683: Inhibition of PARP1 (unknown origin) using histone as substrate by ELISA	ic50	0.0002	uM
5-[4-[(7-ethyl-6-oxo-5H-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl]-N-methylpyridine-2-carboxamide	1896630: Inhibition of PARP-1 (unknown origin)	ic50	0.0003	uM
5-[2-[(7-ethyl-6-oxo-5H-1,5-naphthyridin-3-yl)methyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-N-methylpyridine-2-carboxamide	1896630: Inhibition of PARP-1 (unknown origin)	ic50	0.0003	uM
4-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]-N-[4-[(4-methoxyphenyl)carbamoyl]phenyl]piperazine-1-carboxamide	1868336: Inhibition of PARP-1 (unknown origin) using biotinylated NAD+ as substrate incubated for 45 mins in the presence of deoxy-oligonucleotide by microplate reader method relative to control	ic50	0.0003	uM
2-[[3-[(4-bromobenzoyl)amino]phenyl]methoxy]benzamide	1996188: Inhibition of human PARP-1 by ELISA	ic50	0.0003	uM
4-[[4-fluoro-3-[3-(furan-2-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	2012683: Inhibition of PARP1 (unknown origin) using histone as substrate by ELISA	ic50	0.0003	uM
4-[[3-[3-(chloromethyl)-5-methyl-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one	2138123: Inhibition of PARP1 (unknown origin) incubated for 1 hr by ELISA analysis	ic50	0.0003	uM
4-[[4-fluoro-3-(piperazine-1-carbonyl)phenyl]methyl]-2H-phthalazin-1-one	1515647: Binding affinity to full length His-tagged PARP1 (unknown origin) after 11 mins in presence of NAD+ by TR-FRET assay	ki	0.0004	uM
4-[4-[3-(5-amino-7-fluoro-1-oxo-2H-isoquinolin-3-yl)propyl]piperazin-1-yl]benzamide	1682011: Inhibition of N-terminal GST-tagged human full length PARP1 (2 to 1041 residues) expressed in baculovirus infected Sf9 cells using histone mixture (H2A and H2B) and biotinylated NAD+ as substrate in presence of activated DNA incubated for 60 mins by chemiluminescence assay	ic50	0.0004	uM
4-[[3,4-difluoro-5-[4-(4-nitrophenyl)piperazine-1-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	1499315: Inhibition of PARP1 (unknown origin) by ELISA	ic50	0.0004	uM
4-[[3,4-difluoro-5-[4-(4-fluorophenyl)piperazine-1-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	1499315: Inhibition of PARP1 (unknown origin) by ELISA	ic50	0.0004	uM
4-[[4-fluoro-3-[4-[4-(1H-indazol-4-yl)-6-morpholin-4-yl-1,3,5-triazin-2-yl]piperazine-1-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	1581911: Inhibition of recombinant human PARP1 using histone as substrate after 1 hr in presence of biotinylated NAD+ by ELISA	ic50	0.0004	uM
4-[[3-(7-chloro-3,4-dihydro-1H-pyrazino[1,2-a]benzimidazole-2-carbonyl)-4-fluorophenyl]methyl]-2H-phthalazin-1-one	1764044: Inhibition of PARP1 (unknown origin)	ic50	0.0004	uM
2-[4-[(4-aminopiperidin-1-yl)methyl]phenyl]-6-fluoro-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one	1876450: Inhibition of human PARP1 using NAD+ as substrate incubated for 1 hr by ELISA	ic50	0.0004	uM
3-ethyl-7-[[4-(1H-pyrazolo[5,4-b]pyridin-6-yl)piperazin-1-yl]methyl]-1H-1,5-naphthyridin-2-one	1896630: Inhibition of PARP-1 (unknown origin)	ic50	0.0004	uM
(E)-3-[2-[(7-ethyl-6-oxo-5H-1,5-naphthyridin-3-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]-N-methylprop-2-enamide	1896630: Inhibition of PARP-1 (unknown origin)	ic50	0.0004	uM
6-fluoro-5-[4-[(10-fluoro-5-oxo-6H-pyrrolo[1,2-c]quinazolin-8-yl)methyl]piperazin-1-yl]-N-methylpyridine-2-carboxamide	2128020: Inhibition of N-terminal human PARP1	ic50	0.0004	uM
N,6-dimethyl-5-[4-[(5-oxo-6H-pyrrolo[1,2-c]quinazolin-8-yl)methyl]piperazin-1-yl]pyridine-2-carboxamide	2128020: Inhibition of N-terminal human PARP1	ic50	0.0004	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	2019973: Inhibition of PARP1 (unknown origin) by ELISA assay	ic50	0.0004	uM
4-[[4-fluoro-3-[3-(furan-3-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	2012683: Inhibition of PARP1 (unknown origin) using histone as substrate by ELISA	ic50	0.0004	uM
6-fluoro-N-methyl-5-[4-[(5-oxo-6H-pyrrolo[1,2-c]quinazolin-8-yl)methyl]piperazin-1-yl]pyridine-2-carboxamide	2128020: Inhibition of N-terminal human PARP1	ic50	0.0004	uM
8-[[4-fluoro-3-(4-pyrazin-2-ylpiperazine-1-carbonyl)phenyl]methyl]-2,3,4,6-tetrahydro-1H-pyrido[2,3-d]pyridazin-5-one	673608: Inhibition of PARP1 using [3H]NAD+ after 1 hr by scintillation counting	ki	0.0004	uM
8-[[4-fluoro-3-(4-pyrimidin-2-ylpiperazine-1-carbonyl)phenyl]methyl]-2,3,4,6-tetrahydro-1H-pyrido[2,3-d]pyridazin-5-one	673608: Inhibition of PARP1 using [3H]NAD+ after 1 hr by scintillation counting	ki	0.0004	uM
1-[[3-[(3R)-3,4-diethylpiperazine-1-carbonyl]-4-fluorophenyl]methyl]quinazoline-2,4-dione	1830902: Inhibition of recombinant human PARP1 using NAD+ as substrate incubated for 1 hr by ELISA	ic50	0.0005	uM
4-[[3-(3,4-dihydro-1H-pyrazino[1,2-a]benzimidazole-2-carbonyl)-4-fluorophenyl]methyl]-2H-phthalazin-1-one	1764044: Inhibition of PARP1 (unknown origin)	ic50	0.0005	uM
4-[[3,4-difluoro-5-(4-phenylpiperazine-1-carbonyl)phenyl]methyl]-2H-phthalazin-1-one	1499315: Inhibition of PARP1 (unknown origin) by ELISA	ic50	0.0005	uM
3,3-dimethyl-16-[2-(methylamino)ethyl]-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683888: Inhibition of PARP-1 in human HeLa cells incubated for 18 hrs in presence of H2O2	ec50	0.0005	uM
4-[[4-fluoro-3-(7-fluoro-3,4-dihydro-1H-pyrazino[1,2-a]benzimidazole-2-carbonyl)phenyl]methyl]-2H-phthalazin-1-one	1764044: Inhibition of PARP1 (unknown origin)	ic50	0.0005	uM
4-[[4-fluoro-3-(7-methyl-3,4-dihydro-1H-pyrazino[1,2-a]benzimidazole-2-carbonyl)phenyl]methyl]-2H-phthalazin-1-one	1764044: Inhibition of PARP1 (unknown origin)	ic50	0.0005	uM
5-[[(3R)-1-[(7-ethyl-6-oxo-5H-1,5-naphthyridin-3-yl)methyl]pyrrolidin-3-yl]amino]-N-methylpyridine-2-carboxamide	1896630: Inhibition of PARP-1 (unknown origin)	ic50	0.0005	uM
4-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]-N-[4-[(4-methylphenyl)carbamoyl]phenyl]piperazine-1-carboxamide	1868336: Inhibition of PARP-1 (unknown origin) using biotinylated NAD+ as substrate incubated for 45 mins in the presence of deoxy-oligonucleotide by microplate reader method relative to control	ic50	0.0005	uM

CTD chemical–gene interactions

1100 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetylcysteine	increases expression, increases response to substance, affects abundance, decreases reaction, increases cleavage (+8 more)	72
Arsenic Trioxide	increases degradation, decreases reaction, increases activity, affects localization, decreases expression (+8 more)	64
Doxorubicin	increases expression, decreases response to substance, affects cleavage, affects reaction, affects response to substance (+10 more)	50
Cisplatin	decreases reaction, decreases cleavage, affects cotreatment, affects reaction, decreases expression (+10 more)	42
Quercetin	increases expression, increases response to substance, affects cotreatment, affects reaction, decreases activity (+7 more)	41
sodium arsenite	affects folding, decreases activity, affects reaction, affects binding, increases degradation (+14 more)	40
Resveratrol	increases ADP-ribosylation, decreases expression, increases activity, affects cotreatment, decreases reaction (+9 more)	38
Bortezomib	affects cotreatment, increases cleavage, increases degradation, increases reaction, increases activity (+5 more)	29
pyrazolanthrone	increases expression, increases reaction, increases response to substance, decreases reaction, increases cleavage (+1 more)	26
Hydrogen Peroxide	increases ADP-ribosylation, decreases abundance, affects cotreatment, increases activity, affects reaction (+12 more)	25
benzyloxycarbonyl-valyl-alanyl-aspartic acid	increases response to substance, decreases reaction, increases cleavage, affects cotreatment, increases reaction (+1 more)	24
Paclitaxel	increases expression, affects response to substance, affects cotreatment, increases activity, increases cleavage (+4 more)	20
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone	decreases reaction, increases cleavage, decreases expression, increases expression, affects cotreatment	19
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	increases reaction, increases expression, affects cleavage, decreases activity, increases cleavage (+7 more)	18
3-aminobenzamide	decreases abundance, affects reaction, decreases reaction, increases ADP-ribosylation, increases expression (+7 more)	17
3-methyladenine	increases reaction, increases activity, affects cotreatment, increases cleavage, decreases reaction (+1 more)	17
SB 203580	increases reaction, increases response to substance, decreases cleavage, affects cotreatment, decreases reaction (+1 more)	17
Curcumin	increases cleavage, increases activity, increases degradation, increases expression, decreases expression (+3 more)	17
Plant Extracts	increases cleavage, affects cotreatment, increases expression, decreases expression, decreases reaction	17
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases cleavage, decreases response to substance, increases activity, increases reaction (+1 more)	16
Etoposide	increases cleavage, increases degradation, affects cotreatment, affects reaction, increases reaction (+2 more)	16
Fluorouracil	decreases expression, increases expression, increases cleavage, increases reaction, increases response to substance (+5 more)	16
hydroquinone	increases cleavage, increases degradation, affects response to substance, affects cotreatment, affects binding (+10 more)	15
(+)-JQ1 compound	affects cleavage, increases reaction, affects cotreatment, decreases reaction, increases cleavage (+1 more)	15
Zinc	decreases activity, affects binding, increases cleavage, increases reaction, affects cotreatment (+4 more)	14
Camptothecin	decreases reaction, increases cleavage, increases reaction, increases degradation, affects response to substance (+4 more)	13
U 0126	affects cotreatment, increases cleavage, decreases reaction, increases expression, increases reaction	12
Paraquat	decreases cleavage, increases reaction, affects cotreatment, increases cleavage, decreases reaction (+3 more)	12
Celecoxib	affects cotreatment, increases cleavage, affects cleavage, decreases reaction, increases expression (+2 more)	11
Vorinostat	increases cleavage, affects cotreatment, increases degradation, increases reaction, decreases reaction	11

ChEMBL screening assays

825 unique, capped per target: 814 binding, 8 functional, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1010815	Binding	Inhibition of human recombinant PARP1	Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer. — J Med Chem
CHEMBL4345422	ADMET	Inhibition of recombinant human PARP1 expressed in Escherichia coli assessed as reduction in auto-PARylation using histone as substrate measured after 45 mins in presence of biotinylated-NAD+ by ELISA	Design and Discovery of an Orally Efficacious Spiroindolinone-Based Tankyrase Inhibitor for the Treatment of Colon Cancer. — J Med Chem
CHEMBL5723130	Functional	Affinity Biochemical interaction: (PARP-1 inhibition assay kit (Trevigen)) EUB0002225aCl PARP1	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

14 cell lines: 11 cancer cell line, 2 transformed cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7IH	WAe001-A-63	Embryonic stem cell	Male
CVCL_B3DF	Abcam HEK293T PARP1 KO	Transformed cell line	Female
CVCL_B8ZW	Abcam MCF-7 PARP1 KO	Cancer cell line	Female
CVCL_B9P6	Abcam A-549 PARP1 KO	Cancer cell line	Male
CVCL_D7WK	Ubigene A-549 PARP1 KO	Cancer cell line	Male
CVCL_D8S2	Ubigene HCT 116 PARP1 KO	Cancer cell line	Male
CVCL_D9MB	Ubigene HEK293 PARP1 KO	Transformed cell line	Female
CVCL_E1IW	HyCyte A-549 KO-hPARP1	Cancer cell line	Male
CVCL_E8DH	BPS Bioscience HeLa PARP1 KO	Cancer cell line	Female
CVCL_E8DK	BPS Bioscience MCF-7 PARP1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice

Associated diseases: neurodevelopmental disorder, malignant peripheral nerve sheath tumor, sarcoma, breast carcinoma
Biomarker drugs (CIViC) (drugs whose response is associated with variants in this gene — CIViC predictive evidence, not targeting): Olaparib
Targeted by drugs: Ciclopirox, Fluzoparib, Niraparib, Olaparib, Pamiparib, Rucaparib, Saruparib, Talazoparib
Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): adult malignant schwannoma, breast cancer, breast carcinoma, childhood malignant schwannoma, hereditary renal cell carcinoma, malignant peripheral nerve sheath tumor, melanoma, sarcoma