PARP2 poly(ADP-ribose) polymerase 2
ENSG00000129484 · protein coding · Open Targets profile
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). {ECO:0000269|PubMed:10364231, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:27471034, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29361132, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30321391, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:34108479, ECO:0000269|PubMed:34486521, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Med-Quality Pocket, Druggable Family
- PROTAC
- Literature, Database Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.7330600023269653 (upper bound 0.9139900207519531). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 400 registry trials, updated in the last three years, of the most advanced drugs against PARP2 (veliparib, olaparib, pamiparib, niraparib tosylate monohydrate, rucaparib camsylate, talazoparib, rucaparib, niraparib, senaparib, 2x-121, E-7016), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Amit OzaPrincess Margaret Hospital, Canada · 3 of 3 trials Phase 2+Ph2NCT01081951 · Study to Compare the Efficacy and Safety of Olaparib When Given in Combination With Carboplatin and Paclitaxel, Compared With Carboplatin and Paclitaxel in Patients With Advanced Ovarian Cancerbrief
- Joyce F LiuNRG Oncology · 3 of 3 trials Phase 2+Ph3NCT02446600 · Testing the Use of A Single Drug (Olaparib) or the Combination of Two Drugs (Cediranib and Olaparib) Compared to the Usual Chemotherapy for Women With Platinum Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancerbrief
- Patricia M LoRussoYale University Cancer Center LAO · 3 of 3 trials Phase 2+
- Timothy A YapUniversity of Texas MD Anderson Cancer Center LAO · 2 of 5 trials Phase 2+Ph1NCT04197713 · Testing the Sequential Combination of the Anti-cancer Drugs Olaparib Followed by Adavosertib (AZD1775) in Patients With Advanced Solid Tumors With Selected Mutations and PARP Resistance, STAR Studybrief
- Bradley CorrUniversity of Colorado, Denver · 2 of 3 trials Phase 2+
- Jane RobertsonAstraZeneca · 2 of 3 trials Phase 2+
- A P ChenNational Cancer Institute LAO · 2 of 2 trials Phase 2+
- Andrew TuttGuy's Hospital, Great Maze Pond, London. · 2 of 2 trials Phase 2+
- Benoit YOUHCL - Centre Hospitalier Lyon Sud · 2 of 2 trials Phase 2+
- Fred SaadUniversity of Montreal Hospital Center · 2 of 2 trials Phase 2+
- James GulleyNational Cancer Institute (NCI) · 2 of 2 trials Phase 2+
- Joseph W KimYale University Cancer Center LAO · 2 of 2 trials Phase 2+
- Jung-min LeeNRG Oncology · 2 of 2 trials Phase 2+
- Lillian SiuPrincess Margaret Cancer Centre · 2 of 2 trials Phase 2+
- Noel ClarkeChristie Hospital Foundation Trust · 2 of 2 trials Phase 2+
Registry trials of veliparib, olaparib, pamiparib, niraparib tosylate monohydrate, rucaparib camsylate, talazoparib, rucaparib, niraparib, senaparib, 2x-121, E-7016 updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 283 of 389 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 11 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
164 trials of drugs against PARP2 were stopped early; 9 give no reason
Terminated, withdrawn and suspended interventional trials of veliparib, olaparib, pamiparib, niraparib tosylate monohydrate, rucaparib camsylate, talazoparib, rucaparib, niraparib, senaparib, 2x-121, E-7016, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 164.
- terminated · 2026-11-02 · Peter MacCallum Cancer Centre, Australia · Talazoparib“It was decided to stop the study due to changes in the treatment landscape.”
- withdrawn · 2026-10-30 · Peter MacCallum Cancer Centre, Australia · Olaparib (300 mg BID)“Funding issues”
- withdrawn · 2026-10-20 · Massachusetts General Hospital · Talazoparib“Calithera pulled out of this trial.”
- terminated · 2026-10-19 · Novartis Pharmaceuticals · Olaparib“Sponsor Decision”
- terminated · 2026-09-22 · National Cancer Institute (NCI) · Olaparib“Closed due to slow accrual.”
- terminated · 2026-09-21 · Massachusetts General Hospital · Niraparib“Slow accrual.”
- terminated · 2026-09-14 · Merck Sharp & Dohme LLC · Olaparib“Business Reasons”
- terminated · 2026-08-26 · University of Washington · Rucaparib Camsylate, Rucaparib“Terminated due to insufficient funding”
- terminated · 2026-08-24 · Memorial Sloan Kettering Cancer Center · Talazoparib“Study terminated by sponsor”
- terminated · 2026-08-14 · National Cancer Institute (NCI) · Olaparib“The study was terminated due to low accrual and insufficient efficacy seen in first few participants treated.”
- terminated · 2026-08-13 · National Cancer Institute (NCI) · olaparib“Accrual and drug manufacturing and supply were discontinued in 2025.”
- terminated · 2026-08-03 · Hoffmann-La Roche · Niraparib“Study was closed early as the sponsor decided not to continue development of certain treatment combinations.”
- terminated · 2026-07-22 · Mayo Clinic · Abiraterone Acetate/Niraparib“Sponsor decided to close due to slow accrual and lack of efficacy”
- terminated · 2026-06-29 · University of Iowa · Niraparib“Toxicity in phase 1”
- withdrawn · 2026-06-05 · University of Alabama at Birmingham · M4344+Niraparib“never opened”
- terminated · 2026-06-03 · University of Oklahoma · Niraparib“Funding issue”
- terminated · 2026-06-01 · Allarity Therapeutics · 2X-121 600 mg, 2X-121 800 mg, 2X-121 1000 mg, 2X-121 + 300 mg dovitinib, 2X-121 + 400 mg dovitinib, 2X-121 + 500 mg dovitinib“Sponsor decision.”
- terminated · 2026-05-14 · University of California, Davis · Niraparib, Niraparib Tosylate Monohydrate“PI choice; poor accrual”
- terminated · 2026-04-09 · M.D. Anderson Cancer Center · Olaparib“Sponsor discontinued the trial”
- withdrawn · 2026-04-08 · Qian Qin · Niraparib/Abiraterone Acetate DAT“Funder withdrew funding.”
- terminated · 2026-04-06 · Gustave Roussy, Cancer Campus, Grand Paris · Olaparib“study design, change of standard of care, enrollment difficulties”
- terminated · 2026-02-25 · Gordon Mills, MD, PhD · Olaparib“loss of funding”
- withdrawn · 2026-02-19 · Merck Sharp & Dohme LLC · Olaparib (if approved/available locally)“Since patients were not recruited yet, we would mark this as a Withdrawn status per the NIH definition of that status. Study halted prematurely, prior to enrollment of first participant.”
- terminated · 2026-02-17 · Centre Leon Berard · Niraparib“Study not feasible, patient accrual rate too low.”
- terminated · 2026-02-17 · Leiden University Medical Center · Olaparib Oral Product“recruitment was lower than expected (28/55) due to registration of the IMP in the first and second line treatment”
Paediatric incentives and obligations for PARP2's drugs
For veliparib, olaparib, pamiparib, niraparib tosylate monohydrate, rucaparib camsylate, talazoparib, rucaparib, niraparib, senaparib, 2x-121, E-7016: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · PARP2 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000237870 (senaparib, Treatment of ovarian cancer): W: decision granting a waiver in all age groups for all conditions or indications, 15 Apr 2025; EMA/PE/0000238615 (senaparib, Treatment of peritoneal cancer): W: decision granting a waiver in all age groups for all conditions or indications, 15 Apr 2025; EMA/PE/0000238610 (senaparib, Treatment of fallopian tube cancer): W: decision granting a waiver in all age groups for all conditions or indications, 15 Apr 2025; EMEA-002268-PIP02-18-M02 (niraparib (tosilate monohydrate), Treatment of all conditions included in the category of malignant neoplasms (except haematopoietic and lymphoid tissue neoplasms)): PM: decision on the application for modification of an agreed PIP, 19 Jul 2024; +13 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/10/830 withdrawn 17 Dec 2010: Treatment of ovarian cancer; EU/3/10/760 positive 4 Aug 2010: Treatment of ovarian cancer; EU/3/12/1049 withdrawn 10 Oct 2012: Treatment of ovarian cancer; EU/3/07/501 withdrawn 6 Dec 2007: Treatment of ovarian cancerRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Sepalna: opinion; Rubraca: authorised since 23 May 2018; Akeega: authorised since 19 Apr 2023; Lynparza: authorised since 16 Dec 2014; +2 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of veliparib, olaparib, pamiparib, niraparib tosylate monohydrate, rucaparib camsylate, talazoparib, rucaparib, niraparib, senaparib, 2x-121, e-7016Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 36 interventional studies of veliparib, olaparib, pamiparib, niraparib tosylate monohydrate, rucaparib camsylate, talazoparib, rucaparib, niraparib, senaparib, 2x-121, e-7016 include patients under 18; 16 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 12 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.