ArticleCancers2020
Inhibition of DNA Repair Pathways and Induction of ROS Are Potential Mechanisms of Action of the Small Molecule Inhibitor BOLD-100 in Breast Cancer.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- BOLD-100 treatment induces systemic lipid crosstalk in metastatic colorectal carcinoma patients in a combination treatment with FOLFOX.iScience · 2026Article
- BOLD-100 in Combination with FOLFOX Is a Broadly Effective Therapeutic Strategy for Gastric Cancer.International journal of molecular sciences · 2026Article
- Leveraging Morphological Profiling for Mechanistic Elucidation of Metal-Based Anticancer Compounds.JACS Au · 2026Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- The Role of Metallodrugs in Enhancing Neuroendocrine Neoplasm Therapies: The Promising Anticancer Potential of Ruthenium-Based Complexes.Molecules (Basel, Switzerland) · 2025Review
- Therapeutic potential of BOLD-100, a GRP78 inhibitor, enhanced by ATR inhibition in pancreatic ductal adenocarcinoma.Cell communication and signaling : CCS · 2025Article
- Unraveling BOLD-100 synergistic potential in pleural mesothelioma treatment: an in vitro study.Investigational new drugs · 2025Article
- Platinum-group metal half-sandwich complexes of 1-(α-d-glucopyranosyl)-4-hetaryl-1,2,3-triazoles: synthesis, solution equilibrium studies, and investigation of their anticancer and antimicrobial activities.Frontiers in chemistry · 2025Article
- Insights into Mechanisms and Promising Triple Negative Breast Cancer Therapeutic Potential for a Water-Soluble Ruthenium Compound.ACS pharmacology & translational science · 2024Article
- The Impact of Inorganic Systems and Photoactive Metal Compounds on Cytochrome P450 Enzymes and Metabolism: From Induction to Inhibition.Biomolecules · 2024Review
- Review
- Metals in Cancer Research: Beyond Platinum Metallodrugs.ACS central science · 2024Review
- Complexes of Ruthenium(II) as Promising Dual-Active Agents against Cancer and Viral Infections.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Synthesis and Preclinical Evaluation of Radiolabeled [Pharmaceutics · 2023Article
- The Lipid Metabolism as Target and Modulator of BOLD-100 Anticancer Activity: Crosstalk with Histone Acetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The Metallodrug BOLD-100 Is a Potent Inhibitor of SARS-CoV-2 Replication and Has Broad-Acting Antiviral Activity.Biomolecules · 2023Article
- New Organometallic Ru(II) Compounds with Lonidamine Motif as Antitumor Agents.Pharmaceutics · 2023Article
- Half sandwich-type osmium, ruthenium, iridium and rhodium complexes with bidentate glycosyl heterocyclic ligands induce cytostasis in platinum-resistant ovarian cancer cells and bacteriostasis in Gram-positive multiresistant bacteria.Frontiers in chemistry · 2023Article
- RUNAT-BI: A Ruthenium(III) Complex as a Selective Anti-Tumor Drug Candidate against Highly Aggressive Cancer Cell Lines.Cancers · 2022Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
BOLD-100, a ruthenium-based complex, sodium trans-[tetrachloridobis (1H-indazole) ruthenate (III)] (also known as IT-139, NKP1339 or KP1339), is a novel small molecule drug that demonstrated a manageable safety profile at the maximum tolerated dose and modest antitumor activity in a phase I clinical trial. BOLD-100 has been reported to inhibit the upregulation of the endoplasmic reticulum stress sensing protein GRP78. However, response to BOLD-100 varies in different cancer models and the precise mechanism of action in high-response versus low-response cancer cells remains unclear. In vitro studies have indicated that BOLD-100 induces cytostatic rather than cytotoxic effects as a monotherapy. To understand BOLD-100-mediated signaling mechanism in breast cancer cells, we used estrogen receptor positive (ER+) MCF7 breast cancer cells to obtain gene-metabolite integrated models. At 100 μM, BOLD-100 significantly reduced cell proliferation and expression of genes involved in the DNA repair pathway. BOLD-100 also induced reactive oxygen species (ROS) and phosphorylation of histone H2AX, gamma-H2AX (Ser139), suggesting disruption of proper DNA surveillance. In estrogen receptor negative (ER-) breast cancer cells, combination of BOLD-100 with a PARP inhibitor, olaparib, induced significant inhibition of cell growth and xenografts and increased gamma-H2AX. Thus, BOLD-100 is a novel DNA repair pathway targeting agent and can be used with other chemotherapies in ER- breast cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.