ArticleCancer chemotherapy and pharmacology2009
Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc-Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice.
Article in Cancer chemotherapy and pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 118 citations in OpenAlex.
- Chemical Induction of MYC Protein Degradation via MYC-MAX Disruption and 20S Proteasome Activation.ACS chemical biology · 2026Article
- Prostate cancer cells' growth is decreased by novel MYC inhibitors.Investigational new drugs · 2026Article
- Breaking the bonds: targeting protein dimerization for prostate cancer therapy.Endocrinology · 2026Review
- Pan-cancer Myc modulator that targets Myc-α-tubulin interaction to drive selective mitotic catastrophe.Scientific reports · 2025Article
- Razing the scaffolding: the elimination of non-catalytic functions of kinases through targeted protein degradation.RSC medicinal chemistry · 2025Review
- Beyond the Limit: MYC Mediates Tumor Immune Escape.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Deletion of PTP4A3 phosphatase in high-grade serous ovarian cancer cells decreases tumorigenicity and produces marked changes in intracellular signaling pathways and cytokine release.The Journal of pharmacology and experimental therapeutics · 2025Article
- New insights into protein-protein interaction modulators in drug discovery and therapeutic advance.Signal transduction and targeted therapy · 2024Review
- Anti-Leukemic Effects of Small Molecule Inhibitor of c-Myc (10058-F4) on Chronic Myeloid Leukemia Cells.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Design, synthesis, and activity evaluation of 2-iminobenzimidazoles as c-Myc inhibitors for treating multiple myeloma.Heliyon · 2024Article
- Acetylation of c-Myc at Lysine 148 Protects Neurons After Ischemia.Neuromolecular medicine · 2024Article
- C-Myc inhibition intensified the anti-leukemic properties of Imatinib in chronic myeloid leukemia cells.Molecular biology reports · 2023Article
- Demystifying the Druggability of the MYC Family of Oncogenes.Journal of the American Chemical Society · 2023Review
- A Functional Screening Identifies a New Organic Selenium Compound Targeting Cancer Stem Cells: Role of c-Myc Transcription Activity Inhibition in Liver Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- A Selective Small-Molecule c-Myc Degrader Potently Regresses Lethal c-Myc Overexpressing Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Antitumor Effects of 10058-F4 and Curcumin in Combination Therapy for Pancreatic Cancer In Vitro and In Vivo.Journal of healthcare engineering · 2022Article
- Article
- MYC protein interactors in gene transcription and cancer.Nature reviews. Cancer · 2021Review
- Intestinal MYC modulates obesity-related metabolic dysfunction.Nature metabolism · 2021Article
- Turning Up the Heat on MYC: Progress in Small-Molecule Inhibitors.Cancer research · 2021Review
12 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
7 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesc-Myc is commonly activated in many human tumors and is functionally important in cellular proliferation, differentiation, apoptosis and cell cycle progression. The activity of c-Myc requires noncovalent interaction with its client protein Max. In vitro studies indicate the thioxothiazolidinone, 10058-F4, inhibits c-Myc/Max dimerization. In this study, we report the efficacy, pharmacokinetics and metabolism of this novel protein-protein disruptor in mice.
methodsSCID mice bearing DU145 or PC-3 human prostate cancer xenografts were treated with either 20 or 30 mg/kg 10058-F4 on a qdx5 schedule for 2 weeks for efficacy studies. For pharmacokinetics and metabolism studies, mice bearing PC-3 or DU145 xenografts were treated with 20 mg/kg of 10058-F4 i.v. Plasma and tissues were collected 5-1440 min after dosing. The concentration of 10058-F4 in plasma and tissues was determined by HPLC, and metabolites were characterized by LC-MS/MS.
resultsFollowing a single iv dose, peak plasma 10058-F4 concentrations of approximately 300 muM were seen at 5 min and declined to below the detection limit at 360 min. Plasma concentration versus time data were best approximated by a two-compartment, open, linear model. The highest tissue concentrations of 10058-F4 were found in fat, lung, liver, and kidney. Peak tumor concentrations of 10058-F4 were at least tenfold lower than peak plasma concentrations. Eight metabolites of 10058-F4 were identified in plasma, liver, and kidney. The terminal half-life of 10058-F4 was approximately 1 h, and the volume of distribution was >200 ml/kg. No significant inhibition of tumor growth was seen after i.v. treatment of mice with either 20 or 30 mg/kg 10058-F4.
conclusionThe lack of significant antitumor activity of 10058-F4 in tumor-bearing mice may have resulted from its rapid metabolism and low concentration in tumors.
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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.