ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04644068 (A Modular Phase I/IIa, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies), which is not on this map. Cited by 116 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Modular Phase I/IIa, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies
Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.
- Incidence and risk of endocrine and metabolic abnormalities linked to PARP inhibitors in solid tumors: a meta-analysis.BMC cancer · 2025Pooled it
- Resistance to neoadjuvant talazoparib in triple-negative breast cancer by BRN2-induced ATR/STAT3 pathways or SHLD2 subclone expansion.Proceedings of the National Academy of Sciences of the United States of America · 2026Trial
- Saruparib in combination with androgen receptor pathway inhibitors in metastatic hormone-sensitive prostate cancer: EvoPAR-Prostate01.Future oncology (London, England) · 2026Trial
- Tumor-targeted top1 inhibitor delivery with optimized parp inhibition in advanced solid tumors: a phase i trial of gapped scheduling.Nature communications · 2025Trial
- Antitumor activity and structure-activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- PARP1-selective inhibitor DSB1559 demonstrates superior efficacy and antitumor immunity in triple-negative breast cancer.Journal for immunotherapy of cancer · 2026Article
- Current status of radionuclide therapy targeting PARP in cancer: challenges and prospects.European journal of nuclear medicine and molecular imaging · 2026Review
- Targeting Polθ Helicase with RP-3467: Preclinical Validation and Clinical Response in a gmedRxiv : the preprint server for health sciences · 2026Article
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- Combination of PARPi and topoisomerase I inhibitors is highly effective in olaparib-resistant ovarian cancer.Experimental hematology & oncology · 2026Article
- Gut Microbiota-Isoallolithocholic Acid Crosstalk Promotes Calcium Oxalate Kidney Stone Formation via PARP1-Mediated Parthanatos.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Overcoming Resistance in Triple-Negative Breast Cancer: A Translational Perspective on Next-Generation DNA Damage Response Inhibitors and Synthetic Lethality.Molecules (Basel, Switzerland) · 2026Review
- CRISPR screen identifies autophagy inhibition (GNS561) as a PARP inhibitor (AZD5305) combination strategy in small cell lung cancer.Cancer & metabolism · 2026Article
- Review
- Sequencing PARP inhibitors in breast cancer: lessons learned and emerging insights.NPJ breast cancer · 2026Review
- Comparative Assessment of Free Energy Computational Methods for Revealing the Interactions Driving PARP1 Selective Inhibition.Journal of chemical information and modeling · 2026Article
- PARP2 deficiency impairs pancreatic cancer progression by promoting genomic instability and antitumor immunity.Science advances · 2026Article
- Synthetic lethality in cancer: mechanism exploration and therapeutic applications.Cell communication and signaling : CCS · 2026Review
- Cooperative molecular interaction networks govern PARP1 inhibitor selectivity and binding affinity.PLoS computational biology · 2026Article
- Review
56 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 5 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe hypothesized that inhibition and trapping of PARP1 alone would be sufficient to achieve antitumor activity. In particular, we aimed to achieve selectivity over PARP2, which has been shown to play a role in the survival of hematopoietic/stem progenitor cells in animal models. We developed AZD5305 with the aim of achieving improved clinical efficacy and wider therapeutic window. This next-generation PARP inhibitor (PARPi) could provide a paradigm shift in clinical outcomes achieved by first-generation PARPi, particularly in combination. EXPERIMENTAL
designAZD5305 was tested in vitro for PARylation inhibition, PARP-DNA trapping, and antiproliferative abilities. In vivo efficacy was determined in mouse xenograft and PDX models. The potential for hematologic toxicity was evaluated in rat models, as monotherapy and combination.
resultsAZD5305 is a highly potent and selective inhibitor of PARP1 with 500-fold selectivity for PARP1 over PARP2. AZD5305 inhibits growth in cells with deficiencies in DNA repair, with minimal/no effects in other cells. Unlike first-generation PARPi, AZD5305 has minimal effects on hematologic parameters in a rat pre-clinical model at predicted clinically efficacious exposures. Animal models treated with AZD5305 at doses ≥0.1 mg/kg once daily achieved greater depth of tumor regression compared to olaparib 100 mg/kg once daily, and longer duration of response.
conclusionsAZD5305 potently and selectively inhibits PARP1 resulting in excellent antiproliferative activity and unprecedented selectivity for DNA repair deficient versus proficient cells. These data confirm the hypothesis that targeting only PARP1 can retain the therapeutic benefit of nonselective PARPi, while reducing potential for hematotoxicity. AZD5305 is currently in phase I trials (NCT04644068).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.