PARP1

Poly [ADP-ribose] polymerase 1

Score: 0.657 Price: $0.66 Medium Druggability Status: active Wiki: PARP1

🧠 Neurodegeneration

HYPOTHESES

6

PAPERS

32

KG EDGES

410

DEBATES

1

3D Protein Structure

🧬 PARP1 — PDB 4DQY Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.62

Clinical Stage

Approved

Target Class

Enzyme

Safety

0.60

Druggability Analysis

Drug Development1.00

Structural Tractability0.95

Target Class0.85

Safety Profile0.60

Key Metrics

PDB Structures:

97

Known Drugs:

3

Approved:

3

In Clinical Trials:

0

Drug Pipeline (3 compounds)

3 Approved

Druggability Rationale: PARP1 is highly druggable due to its well-defined catalytic domain with a deep ATP-binding pocket, demonstrated by 97 PDB structures at 1.5Å resolution and three FDA-approved inhibitors (olaparib, niraparib, rucaparib) already in clinical use. The enzyme's established role in DNA repair and validated mechanism of action as a competitive inhibitor provides a clear therapeutic window for both oncology and neuroprotection applications.

Mechanism: Competitive inhibitors of PARP1 enzymatic activity blocking DNA repair

Drug Pipeline (3 compounds)

3 Approved

Known Drugs:

Olaparib (approved) — BRCA-mutated cancers

Niraparib (approved) — ovarian cancer

Rucaparib (approved) — ovarian cancer

Structural Data:

PDB (97) ✓AlphaFold ✓Cryo-EM ✓

2COK 2CR9 2CS2 2JVN 2L30+92 more

UniProt: Q05D33

🧬 3D Protein Structure

🧬 PARP1 — PDB 4DQY Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

PARP1 inhibition presents moderate selectivity challenges due to structural homology with other PARP family members (PARP2-PARP17), risking off-target activity; however, existing approved drugs demonstrate achievable selectivity through careful chemical design. Isoform-selective inhibitors have been developed to minimize off-target effects and potentially improve therapeutic index in neuroprotection applications.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (8)

Relevant trials from ClinicalTrials.gov

Active

6

Completed

2

Total Enrollment

803

By Phase

PHASE1: 1 · PHASE2: 5 · PHASE4: 1 · Unknown: 1

Pembrolizumab and Olaparib Treatment of Extensive Small Cell Lung Cancer (ES-SCLC) Recruiting

PHASE2 NCT05623319 n=60

SCLC,Extensive Stage

Interventions: Pembrolizumab/Olaparib

Sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRS | Started: 2023-03-27

Investigating Idetrexed and Olaparib in Patients With Ovarian Cancer Recruiting

PHASE1 NCT06976892 n=33

High Grade Serous Ovarian Cancer

Interventions: Dose Level 2 (starting dose), Dose Level 1, Dose Level -1

Sponsor: Institute of Cancer Research, United Kingdom | Started: 2025-08

PRostate Olaparib Real World Evidence Study Recruiting

Unknown NCT06031805 n=300

Metastatic Castration-resistant Prostate

Sponsor: AstraZeneca | Started: 2023-10-11

PARP-inhibitor on Advanced Metastatic Breast Cancer in Germline PALB2 Mutations Carriers Not Yet Recruiting

PHASE2 NCT05232006 n=12

Metastatic Breast Cancer in Germline-PAL

Interventions: Niraparib

Sponsor: Assistance Publique - Hôpitaux de Paris | Started: 2022-05

Olaparib, Durvalumab and UV1 in Relapsed Ovarian Cancer Active Not Recruiting

PHASE2 NCT04742075 n=188

Ovarian Cancer

Interventions: Olaparib + durvalumab + UV1

Sponsor: Nordic Society of Gynaecological Oncology - Clinical Trials | Started: 2021-12-15

Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302) Active Not Recruiting

PHASE2 NCT06433219 n=63

Ovarian Cancer

Interventions: Tuvusertib (M1774), Niraparib, Lartesertib (M4076)

Sponsor: EMD Serono Research & Development Institute, Inc. | Started: 2024-10-30

NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib. Completed

PHASE4 NCT03752216 n=141

Ovarian Cancer

Interventions: Niraparib

Sponsor: ARCAGY/ GINECO GROUP | Started: 2019-04-03

Anlotinib Combined With Niraparib Dual Therapy in Platinum-resistant Recurrent Ovarian Clear Cell Carcinoma. Completed

PHASE2 NCT05130515 n=6

Platinum-resistant Recurrent Clear Cell

Interventions: Niraparib, Anlotinib

Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Started: 2021-12-15

Linked Hypotheses (3)

PARP1 Inhibition Therapy0.738

PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Subsequent p53 Activation0.661

Oligodendrocyte DNA Repair Enhancement0.550

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (3)

FAS→PARP1TNF→PARP1IL6→PARP1

associated with (1)

PARP1→neurodegeneration

co discussed (6)

TGM2→PARP1PRMT1→PARP1PARP1→HSPA1APARP1→G3BP1PARP1→SRPK1

▸ Show 1 more

interacts with (10)

NCSTN→PARP1LMNA→PARP1APH1B→PARP1APOE→PARP1SREBF1→PARP1

▸ Show 5 more

PSEN2→PARP1A2M→PARP1DHCR24→PARP1HMGCR→PARP1MAPT→PARP1

Debate History (1)

Should PARP1 (Poly [ADP-ribose] polymerase 1) be prioritized as a therapeutic ta2026-04-21