ArticleInvestigational new drugs2016
Molecular mode of action of NKP-1339 - a clinically investigated ruthenium-based drug - involves ER- and ROS-related effects in colon carcinoma cell lines.
Article in Investigational new drugs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Importance of PERK pathway modulation on colorectal cancer management: a systematic review.BMC cancer · 2025Pooled it
- New Ru(III) NAMI/NAMI-A Analogue Complexes with Selective Anticancer Activity.Journal of medicinal chemistry · 2026Article
- Combinational studies of BOLD-100/KP1339 with established chemotherapeutics in gastrointestinal multicellular tumor spheroids.Cancer chemotherapy and pharmacology · 2026Article
- How to Use Quantum Computers for Biomolecular Free Energies.Journal of chemical theory and computation · 2026Article
- The Role of Metallodrugs in Enhancing Neuroendocrine Neoplasm Therapies: The Promising Anticancer Potential of Ruthenium-Based Complexes.Molecules (Basel, Switzerland) · 2025Review
- Endoplasmic reticulum stress responses in anticancer immunity.Nature reviews. Cancer · 2025Review
- Machine Learning-Enhanced Calculation of Quantum-Classical Binding Free Energies.Journal of chemical theory and computation · 2025Article
- Therapeutic potential of BOLD-100, a GRP78 inhibitor, enhanced by ATR inhibition in pancreatic ductal adenocarcinoma.Cell communication and signaling : CCS · 2025Article
- Metal-based immunogenic cell death inducers for cancer immunotherapy.Chemical science · 2025Review
- Article
- Complexes of Ruthenium(II) as Promising Dual-Active Agents against Cancer and Viral Infections.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Research Progress of Metal Anticancer Drugs.Pharmaceutics · 2023Review
- The Lipid Metabolism as Target and Modulator of BOLD-100 Anticancer Activity: Crosstalk with Histone Acetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Mechanistic Studies of Arene-Ruthenium(II) Complexes with Carbothioamidopyrazoles as Alternative Cancer Drugs.Molecules (Basel, Switzerland) · 2023Article
- Increasing Stress to Induce Apoptosis in Pancreatic Cancer via the Unfolded Protein Response (UPR).International journal of molecular sciences · 2022Review
- Article
- Metallo-Drugs in Cancer Therapy: Past, Present and Future.Molecules (Basel, Switzerland) · 2022Review
- Article
- Factors that influence singlet oxygen formation vs. ligand substitution for light-activated ruthenium anticancer compounds.Current opinion in chemical biology · 2022Review
- Metallodrugs: an approach against invasion and metastasis in cancer treatment.FEBS open bio · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (NKP-1339) is a clinically investigated ruthenium-based metal complex, which shows promising results in solid tumors, such as non-small cell lung cancer, colorectal carcinoma, and most distinctively in gastrointestinal neuroendocrine tumors. In previous studies, fast binding to albumin as well as transferrin could be shown. The enhanced permeability and retention (EPR) effect, which is diversely being exploited for tumor targeting, could therefore be applicable for NKP-1339. Here we studied the serum dependence of its biological activity in various methods, influencing its cellular accumulation, cytotoxicity as well as the generation of reactive oxygen species (ROS). ROS lead to Nrf2 activation, which is known to activate antioxidant response gene transcription. GRP78 down-regulation on the protein level suggests ER associated protein degradation (ERAD) as a mode of action, as RNA levels are only mildly affected. Another important part for the mode of action is endoplasmic reticulum (ER) stress, as different factors are highly upregulated on the protein level. For example PERK, a transmembrane receptor which is released by GRP78 when the ER is disturbed, is upregulated and phosphorylated. EIF2α is phosphorylated, which leads to an inhibition of CAP-dependent translation and other stress responses. The transcription factor CHOP (DDIT3), which promotes ER stress dependent apoptosis, is time and concentration dependently upregulated. Finally cytotoxicity tests could prove that inhibition of ER stress and ER stress-mediated apoptosis leads to decreased cytotoxic effects of NKP-1339, which highlights the involvement of this mechanism in the mode of action.
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