Protein / target

Poly [ADP-ribose] polymerase 2

Encoded byPARP2Q9UGN5Homo sapiensSwiss-Prot

UniProt: Q9UGN5 Ensembl: ENSG00000129484 HGNC: HGNC:272 NCBI Gene: 10038

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Approved Drug

Protein at a glance

Biological role

Poly-ADP-D-ribose modification-dependent protein binding

Strongest disease association

Ovarian Neoplasms

Via encoding gene PARP2 · Clinical evidence · score 0.60

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.

View complete UniProt function annotation

Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:10364231, PubMed:25043379, PubMed:27471034, PubMed:30104678, PubMed:32028527, PubMed:32939087, PubMed:34108479, PubMed:34486521, PubMed:34874266). 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 (PubMed:25043379, PubMed:30104678, PubMed:30321391). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:32939087). Mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1 (PubMed:25043379). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP2 active site (PubMed:28190768, PubMed:32028527, PubMed:34108479, PubMed:34486521, PubMed:34874266). 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 (PubMed:10364231, PubMed:32939087, PubMed:34108479). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP2 in order to limit the length of poly-ADP-ribose chains (PubMed:34732825, PubMed:34795260). Specifically mediates formation of branched poly-ADP-ribosylation (PubMed:30104678). Branched poly-ADP-ribose chains are specifically recognized by some factors, such as APLF (PubMed:30104678). In addition to proteins, also able to ADP-ribosylate DNA: preferentially acts on 5'-terminal phosphates at DNA strand breaks termini in nicked duplex (PubMed:27471034, PubMed:29361132)

Subcellular location

NucleusChromosome

Domains and Gene Ontology detail (27)

Domains & features

WGRPARP alpha-helicalPARP catalytic

Gene Ontology

Cnucleolus
Cnucleoplasm
Cnucleus
Csite of DNA damage
Fchromatin binding
Fdamaged DNA binding
FNAD DNA ADP-ribosyltransferase activity
FNAD+ poly-ADP-ribosyltransferase activity
FNAD+-protein mono-ADP-ribosyltransferase activity
FNAD+-protein-aspartate ADP-ribosyltransferase activity
FNAD+-protein-glutamate ADP-ribosyltransferase activity
FNAD+-protein-serine ADP-ribosyltransferase activity

583 aa · 66 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Metabolic enzyme activityGO

View supporting evidence

Metabolic enzyme activity

·NAD DNA ADP-ribosyltransferase activity
·NAD+ poly-ADP-ribosyltransferase activity
·NAD+-protein mono-ADP-ribosyltransferase activity
·NAD+-protein-aspartate ADP-ribosyltransferase activity

View underlying pathways (5)

POLB-Dependent Long Patch Base Excision Repair

HDR through MMEJ (alt-NHEJ)

DNA Damage Recognition in GG-NER

Formation of Incision Complex in GG-NER

Dual Incision in GG-NER

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

3 medicines · 5 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Breast Neoplasms1 medicine

olaparib

Ovarian Neoplasms1 medicine

olaparib

Pancreatic Neoplasms1 medicine

olaparib

Prostatic Neoplasms, Castration-Resistant1 medicine

olaparib

Neoplasms3 medicines

niraparib olaparib rucaparib

9 medicines meet Open Targets' target-level approved-medicine definition; the 3 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

talazoparib

Narrow target profileApprovedInhibitor

Poly [ADP-ribose] polymerase 2 inhibitor

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

niraparib

Narrow target profileApprovedInhibitor

Poly [ADP-ribose] polymerase 2 inhibitor

Indicated for Neoplasms

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

olaparib

ApprovedInhibitor

PARP 1, 2 and 3 inhibitor

Indicated for Breast Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Prostatic Neoplasms, Castration-Resistant

Acts on a complex — shared with PARP1, PARP3 · 1 of 3 recorded protein targets — narrow recorded profile

rucaparib

ApprovedInhibitor

PARP 1, 2 and 3 inhibitor

Indicated for Neoplasms

Acts on a complex — shared with PARP1, PARP3 · 1 of 3 recorded protein targets — narrow recorded profile

veliparib

ApprovedInhibitor

PARP 1, 2 and 3 inhibitor

Acts on a complex — shared with PARP1, PARP3 · 1 of 3 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene PARP2

Gene-level evidence surfaced through the gene PARP2that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Ovarian Neoplasms

0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Neoplasms

0.71Moderately supported

Clinical evidence dominant · Open Targets 0.57

Breast Neoplasms

0.69Moderately supported

Clinical evidence dominant · Open Targets 0.56

Ovarian carcinoma

0.68Moderately supported

Clinical evidence dominant · Open Targets 0.55

Prostatic Neoplasms

0.65Moderately supported

Clinical evidence dominant · Open Targets 0.52

View evidence synthesis (5)

Ovarian NeoplasmsModerately supported

0.74

agreement 0.58–0.89

Clinical97%Literature3%

Open Targets aggregate 0.60 · 2 independent evidence families

NeoplasmsModerately supported

0.71

agreement 0.56–0.87

Clinical90%Literature10%

Open Targets aggregate 0.57 · 2 independent evidence families

Breast NeoplasmsModerately supported

0.69

agreement 0.53–0.84

Clinical95%Literature5%

Open Targets aggregate 0.56 · 2 independent evidence families

Ovarian carcinomaModerately supported

0.68

agreement 0.52–0.83

Clinical97%Literature3%

Open Targets aggregate 0.55 · 2 independent evidence families

Prostatic NeoplasmsModerately supported

0.65

agreement 0.49–0.80

Clinical98%Literature2%

Open Targets aggregate 0.52 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Ovarian Neoplasms0.60

Neoplasms0.57

Breast Neoplasms0.56

Ovarian carcinoma0.55

Prostatic Neoplasms0.52

Ovarian neoplasm0.50

Peritoneum cancer0.50

Drug development

12 compounds recorded · 9 approved · 3 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 5 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)

NIRAPARIBApproval

VELIPARIBApproval

SENAPARIBPhase 3

OLAPARIBApproval

PAMIPARIBApproval

2X-121Phase 2

NIRAPARIB TOSYLATE MONOHYDRATEApproval

RUCAPARIB CAMSYLATEApproval

TALAZOPARIBApproval

E-7016Phase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Protein degraders — Emerging

Feasibility evidence (literature and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · Druggable FamilyPR · LiteraturePR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

A Phase IV Trial to Confirm the Efficacy of Olaparib in Combination With Bevacizumab as Frontline Treatment of HRD Positive Ovarian TumorsPHASE4

ACTIVE_NOT_RECRUITING · via olaparib · NCT06121401

A Phase 3, Open-label, Randomized 2-arm Study Comparing the Clinical Efficacy and Safety of Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated GlioblastomaPHASE3

ACTIVE_NOT_RECRUITING · via niraparib · NCT06388733

AVELUMAB MASTER PROTOCOL: AN OPEN-LABEL CONTINUATION STUDY FOR PARTICIPANTS CONTINUING FROM PFIZER-SPONSORED AVELUMAB CLINICAL STUDIES.PHASE3

ACTIVE_NOT_RECRUITING · via talazoparib · NCT05059522

Niraparib vs Niraparib in Combination With Bevacizumab in Patients With Carboplatinum-taxane Based Chemotherapy in Advanced Ovarian Cancer (A Multicentre Randomised Phase III Trial)PHASE3

RECRUITING · via niraparib · NCT05009082

View all trials (26)

A Randomised, Double-blind, Placebo-controlled, Phase III Study of Olaparib Maintenance Monotherapy in Participants With BRCA Wild Type Advanced High Grade Serous or Endometrioid Ovarian Cancer Following Response to Standard First-line Platinum-based Chemotherapy (MONO-OLA1)PHASE3

ACTIVE_NOT_RECRUITING · via olaparib · NCT04884360

A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Subjects With Metastatic Prostate CancerPHASE3

ACTIVE_NOT_RECRUITING · via niraparib · NCT03748641

A Phase III Study Comparing Single-Agent Olaparib or the Combination of Cediranib and Olaparib to Standard Platinum-Based Chemotherapy in Women With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal CancerPHASE3

ACTIVE_NOT_RECRUITING · via olaparib · NCT02446600

Phase III Randomised, Double Blind, Placebo Controlled Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed BRCA Mutated Ovarian Cancer Patients With a Complete or Partial Response Following Platinum Based ChemotherapyPHASE3

ACTIVE_NOT_RECRUITING · via olaparib · NCT01874353

An Open-label, Single-arm, Single-center Exploratory Clinical Study of Olaparib in the Treatment of BRCA1/2 Unmutated and BRCA1 Promoter Methylated Recurrent and Metastatic Triple-negative Breast CancerPHASE2

NOT_YET_RECRUITING · via olaparib · NCT05522491

A Prospective, Open-label, Multicenter Phase II Clinical Study of Iparomlimab and Tuvonralimab (QL1706) Combined With Standard Chemotherapy or Combined With Intraperitoneal Perfusion Chemotherapy and Olaparib as Neoadjuvant Therapy for Advanced Ovarian CancerPHASE2

NOT_YET_RECRUITING · via olaparib · NCT07407452

Presurgical Phase II Study of Talazoparib in Combination With Enzalutamide in de Novo Metastatic to Lymph Nodes Prostate CancerPHASE2

RECRUITING · via talazoparib · NCT05873192

A Phase 1/2, Open Label Trial to Investigate the Safety, Tolerability, and Preliminary Efficacy of EIS-12656 as Single Agent and in Combination With a Poly-ADP Ribose Polymerase (PARP) Inhibitor or Trastuzumab Deruxtecan (T-DXd), an Antibody Drug Conjugate (ADC), in Participants With Specified Solid TumorsPHASE1/PHASE2

RECRUITING · via olaparib · NCT06525298

Neoadjuvant and Adjuvant Olaparib Plus Pembrolizumab Following Platinum Based Chemotherapy Plus Pembrolizumab for Germline BRCA Mutated Triple Negative Breast Cancer (WJOG14020B/OPERETTA)PHASE2

RECRUITING · via olaparib · NCT05485766

MK-5684-01A Substudy: A Phase 1/2 Umbrella Substudy of MK-5684-U01 Master Protocol to Evaluate the Safety and Efficacy of MK-5684-based Treatment Combinations or MK-5684 Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC)PHASE1/PHASE2

RECRUITING · via olaparib · NCT06353386

A Pilot Study of Neoadjuvant Response-Adapted Chemotherapy With Pembrolizumab in Patients With Stage 2 and 3 Triple Negative Breast Cancer to Determine Early PET and Biomarker DynamicsPHASE2

RECRUITING · via olaparib · NCT06245889

Phase Ib/II Non-randomized Non-comparative Two-cohort Study of Niraparib and Dostarlimab Plus (Chemo)RadIotherapy in Locally-Advanced Head and Neck Squamous Cell CarcinomaPHASE1/PHASE2

ACTIVE_NOT_RECRUITING · via niraparib · NCT05784012

A Phase 1/2 First-Time-in-Human, Open-label, Multicenter, Dose Escalation and Expansion Study of the Oral DNA Polymerase Theta Inhibitor (POLQi) GSK4524101 and the PARP Inhibitor (PARPi) Niraparib in Adult Participants With Solid TumorsPHASE1/PHASE2

ACTIVE_NOT_RECRUITING · via niraparib · NCT06077877

A Phase II Evaluation of Maintenance Therapy Combination Mirvetuximab Soravtansine-gynx and Olaparib in Recurrent Platinum Sensitive Ovarian, Peritoneal, and Fallopian Tube CancerPHASE2

RECRUITING · via olaparib · NCT05887609

A Liquid-biopsy Informed Platform Trial to Evaluate Treatment in CDK4/6-inhibitor Resistant ER+/HER2- Metastatic Breast CancerPHASE2

RECRUITING · via niraparib · NCT05601440

A Surgical "Window-of-Opportunity" and Phase II Trial of Pembrolizumab, Olaparib and Temozolomide in Recurrent GlioblastomaPHASE2

RECRUITING · via olaparib · NCT05463848

Phase I/II Study of Lu-177-DOTATATE (Lutathera) in Combination With Olaparib in Inoperable Gastroenteropancreatico Neuroendocrine Tumors (GEP-NET)PHASE1/PHASE2

RECRUITING · via olaparib · NCT04086485

Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE CANCER) Trial: RARE 2 Talazoparib and TemozolomidePHASE2

ACTIVE_NOT_RECRUITING · via talazoparib · NCT05142241

Phase II, Two-cohorts, Randomized Trial Comparing Standard of Care Versus Immune- Based Combination in Relapsed Stage III Non-small-cell Lung Cancer (NSCLC) Pretreated With Chemoradiotherapy and Durvalumab (MEDI4736)PHASE2

RECRUITING · via olaparib · NCT05568212

Randomized Open-labeled Phase 2 Study of Maintenance Olaparib With or Without Durvalumab for DDR Gene Mutated Advanced Biliary Tract Cancer Following Platinum-based ChemotherapyPHASE2

RECRUITING · via olaparib · NCT05222971

Olaparib in Combination With Pembrolizumab and Carboplatin as First-Line Treatment of Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma: A Single-Arm, Phase 2 TrialPHASE2

ACTIVE_NOT_RECRUITING · via olaparib · NCT04643379

Phase II Trial of Primary Radiotherapy With Androgen Ablation With or Without Adjuvant Niraparib for Selected High-Risk Locoregional Prostate CancerPHASE2

RECRUITING · via niraparib · NCT04947254

APOLLO: A Randomized Phase II Double-Blind Study of Olaparib Versus Placebo Following Curative Intent Therapy in Patients With Resected Pancreatic Cancer and a Pathogenic BRCA1, BRCA2 or PALB2 MutationPHASE2

RECRUITING · via olaparib · NCT04858334

A Randomized Phase II Trial of Triplet Therapy (A PD-L1 Inhibitor Durvalumab (MEDI4736) in Combination With Olaparib and Cediranib) Compared to Olaparib and Cediranib or Durvalumab (MEDI4736) and Cediranib or Standard of Care Chemotherapy in Women With Platinum-Resistant Recurrent Epithelial Ovarian Cancer, Primary Peritoneal or Fallopian Cancer Who Have Received Prior BevacizumabPHASE2

ACTIVE_NOT_RECRUITING · via olaparib · NCT04739800

A Randomized Phase I/II Study of Talazoparib or Temozolomide in Combination With Onivyde in Children With Recurrent Solid Malignancies and Ewing SarcomaPHASE1/PHASE2

RECRUITING · via talazoparib · NCT04901702

A Pharmacodynamics-Driven Trial of Talazoparib, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Aberrations in Genes Involved in DNA Damage ResponsePHASE2

ACTIVE_NOT_RECRUITING · via talazoparib · NCT04550494

ClinicalTrials.gov via the drug-target graph.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 4 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

Trial status changed2026-07-21
A Phase 1, Open-Label, Multicenter Study of INCB123667 as Monotherapy and in Combination With Anticancer Therapies in Participants With Selected Advanced Solid Tumors
Status changed to Active, not recruiting · ClinicalTrials.gov · via olaparib
Trial results posted2026-07-17
Phase II Study of Rucaparib and Nivolumab in Patients With Leiomyosarcoma
Results posted · ClinicalTrials.gov · via rucaparib
Trial status changed2026-07-16
A Pharmacodynamics-Driven Trial of Talazoparib, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Aberrations in Genes Involved in DNA Damage Response
Status changed to Active, not recruiting · ClinicalTrials.gov · via talazoparib
New publication2025-10-07
Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial.
Nature medicine · 2025 · 19 citations · Europe PMC · via niraparib
New publication2025-01-31
Results of a phase Ib study of olaparib with concomitant radiotherapy in soft-tissue sarcoma: a French sarcoma group study.
Annals of oncology : official journal of the European Society for Medical Oncology · 2025 · 4 citations · Europe PMC · via olaparib
New publication2023-12-04
First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial.
Nature medicine · 2024 · 105 citations · Europe PMC · via talazoparib
New publication2023-11-14
Olaparib for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer and Alterations in BRCA1 and/or BRCA2 in the PROfound Trial.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024 · 76 citations · Europe PMC · via olaparib
Safety communication2022-09-26
Drug Safety Update: Rucaparib (Rubraca▼): withdrawal of third-line treatment indication
mhra · safety · mhra · via rucaparib
Safety communication2020-10-22
Drug Safety Update: Niraparib (Zejula▼): reports of severe hypertension and posterior reversible encephalopathy syndrome (PRES), particularly in early treatment
mhra · safety · mhra · via niraparib
Regulatory approval2019-06-20
Approval: Talzenna (EMA)
ema · regulatory · ema · via talazoparib
Regulatory approval2017-11-16
Approval: Zejula (EMA)
ema · regulatory · ema · via niraparib
Regulatory approval2014-12-16
Approval: Lynparza (EMA)
ema · regulatory · ema · via olaparib

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.

Related family literature

Papers about “Poly(ADP-ribose) Polymerases” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models.

Wong CW · Nature communications · 2023

via Poly(ADP-ribose) Polymerases

NAD+ homeostasis in renal health and disease.

Ralto KM · Nature reviews. Nephrology · 2020

via Poly(ADP-ribose) Polymerases

PARP and PARG inhibitors in cancer treatment.

Slade D · Genes & development · 2020

via Poly(ADP-ribose) Polymerases

Circular RNA TLK1 Aggravates Neuronal Injury and Neurological Deficits after Ischemic Stroke via miR-335-3p/TIPARP.

Wu F · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019

via Poly(ADP-ribose) Polymerases

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.