ArticleJournal of medicinal chemistry2020
Cancer Cell Resistance Against the Clinically Investigated Thiosemicarbazone COTI-2 Is Based on Formation of Intracellular Copper Complex Glutathione Adducts and ABCC1-Mediated Efflux.
Article in Journal of medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- A Tale of Two Mechanisms: The p53 Modulator COTI-2 Is a Zn Metallochaperone.Drug development research · 2026Article
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Structure-Activity Relationships of Silver(I)- and Gold(I)-NHC Complexes Reveal Distinctly Different Responses of Cisplatin-Resistant Ovarian Cancer to Bis-NHC-Gold(I) Derivatives.Journal of medicinal chemistry · 2026Article
- The Synthesis, Metal Exchange, and Hyaluronate Functionalization of a Cationic Gallium-Based Thiosemicarbazone Anticancer Drug.Molecules (Basel, Switzerland) · 2026Article
- ABC Transporter Protein-mediated Multidrug Resistance in Breast Cancer and Development of Targeting Strategies.Recent patents on anti-cancer drug discovery · 2026Review
- Recent Advances in Synthetic Isoquinoline-Based Derivatives in Drug Design.Molecules (Basel, Switzerland) · 2025Review
- ABCC1 promotes GSH-dependent iron transport and resistance to Fe(II) and Cu(II) chelators.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- Lysosome as a Chemical Reactor.International journal of molecular sciences · 2025Review
- Palladium(II) Complexes with Noncovalent Interactions with DNA: Solution Speciation Controlled by Solvent Identity, pH, and Concentration.Inorganic chemistry · 2025Article
- Transmetalation in Cancer Pharmacology.International journal of molecular sciences · 2025Review
- Unveiling the Cuproptosis in Colitis and Colitis-Related Carcinogenesis: A Multifaceted Player and Immune Moderator.Research (Washington, D.C.) · 2025Review
- Synthesis and Characterization of Novel Co(III)/Ru(II) Heterobimetallic Complexes as Hypoxia-Activated Iron-Sequestering Anticancer Prodrugs.Molecules (Basel, Switzerland) · 2024Article
- Thiazole Functionalization of Thiosemicarbazone for Cu(II) Complexation: Moving toward Highly Efficient Anticancer Drugs with Promising Oral Bioavailability.Molecules (Basel, Switzerland) · 2024Article
- Copper(II) Complexes with Isomeric Morpholine-Substituted 2-Formylpyridine Thiosemicarbazone Hybrids as Potential Anticancer Drugs Inhibiting Both Ribonucleotide Reductase and Tubulin Polymerization: The Morpholine Position Matters.Journal of medicinal chemistry · 2024Article
- Review
- Metal nanoparticles for cancer therapy: Precision targeting of DNA damage.Acta pharmaceutica Sinica. B · 2024Review
- Aminoquinoline-Based Tridentate (Molecules (Basel, Switzerland) · 2024Article
- Desulfurization of thiosemicarbazones: the role of metal ions and biological implications.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024Review
- Human serum albumin as a copper source for anticancer thiosemicarbazones.Metallomics : integrated biometal science · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
COTI-2 is a novel anticancer thiosemicarbazone in phase I clinical trial. However, the effects of metal complexation (a main characteristic of thiosemicarbazones) and acquired resistance mechanisms are widely unknown. Therefore, in this study, the copper and iron complexes of COTI-2 were synthesized and evaluated for their anticancer activity and impact on drug resistance in comparison to metal-free thiosemicarbazones. Investigations using Triapine-resistant SW480/Tria and newly established COTI-2-resistant SW480/Coti cells revealed distinct structure-activity relationships. SW480/Coti cells were found to overexpress ABCC1, and COTI-2 being a substrate for this efflux pump. This was unexpected, as ABCC1 has strong selectivity for glutathione adducts. The recognition by ABCC1 could be explained by the reduction kinetics of a ternary Cu-COTI-2 complex with glutathione. Thus, only thiosemicarbazones forming stable, nonreducible copper(II)-glutathione adducts are recognized and, in turn, effluxed by ABCC1. This reveals a crucial connection between copper complex chemistry, glutathione interaction, and the resistance profile of clinically relevant thiosemicarbazones.
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.