ArticleJournal of medicinal chemistry2023
Discovery of Ruthenium(II) Metallocompound and Olaparib Synergy for Cancer Combination Therapy.
Article in Journal of medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The trial behind it
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- Ruthenium(ii) polypyridyl complexes and the DNA damage response: mechanisms and therapeutic implications.RSC medicinal chemistry · 2026Review
- Combinational studies of BOLD-100/KP1339 with established chemotherapeutics in gastrointestinal multicellular tumor spheroids.Cancer chemotherapy and pharmacology · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- The golden touch: a comprehensive network pharmacology-guided review of synergy between curcumin and PARP inhibitors.Medical oncology (Northwood, London, England) · 2025Review
- Olaparib synergy screen reveals Exemestane induces replication stress in triple-negative breast cancer.Molecular oncology · 2025Article
- Ru(II)-based complexes containing 2-thiouracil derivatives suppress liver cancer stem cells by targeting NF-κB and Akt/mTOR signaling.Cell death discovery · 2024Article
- Tracking the cellular uptake and phototoxicity of Ru(ii)-polypyridyl-1,8-naphthalimide Tröger's base conjugates.RSC chemical biology · 2024Article
- A Progressively Disassembled DNA Repair Inhibitors Nanosystem for the Treatment of BRCA Wild-Type Triple-Negative Breast Cancer.International journal of nanomedicine · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synergistic drug combinations can extend the use of poly(ADP-ribose) polymerase inhibitors (PARPi) such as Olaparib to BRCA-proficient tumors and overcome acquired or de novo drug resistance. To identify new synergistic combinations for PARPi, we screened a "micro-library" comprising a mix of commercially available drugs and DNA-binding ruthenium(II) polypyridyl complexes (RPCs) for Olaparib synergy in BRCA-proficient triple-negative breast cancer cells. This identified three hits: the natural product Curcumin and two ruthenium(II)-rhenium(I) polypyridyl metallomacrocycles. All combinations identified were effective in BRCA-proficient breast cancer cells, including an Olaparib-resistant cell line, and spheroid models. Mechanistic studies indicated that synergy was achieved via DNA-damage enhancement and resultant apoptosis. Combinations showed low cytotoxicity toward non-malignant breast epithelial cells and low acute and developmental toxicity in zebrafish embryos. This work identifies RPC metallomacrocycles as a novel class of agents for cancer combination therapy and provides a proof of concept for the inclusion of metallocompounds within drug synergy screens.
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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.