ArticleThoracic cancer2025
ACT001 Suppresses the Malignant Progression of Small-Cell Lung Cancer by Inhibiting Lactate Production and Promoting Anti-Tumor Immunity.
Article in Thoracic cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- ACT001 suppresses ox-LDL-mediated macrophage ferroptosis via activating the NRF2 pathway: AnExperimental and therapeutic medicine · 2026Article
- Monocarboxylate Transporter 2 (MCT2) Reduction Is Associated with Increased Lung Tumor Growth and Alterations in the Immune Microenvironment in a Subcutaneous Tumor Model.International journal of molecular sciences · 2026Article
- Redox Homeostasis, Metabolic Pathways and Plasticity in Uveal Melanoma Compared to Other Cancers.Cancers · 2026Review
- Identification ofMolecular medicine reports · 2026Article
- ACT001 alleviates sepsis-induced acute lung injury by downregulating PANoptosis via the JAK2/STAT3 pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Metabolic crosstalk among cancer-associated fibroblasts, adipocytes and immune cells as an immunosuppressive tumor microenvironment driver.Experimental & molecular medicine · 2026Review
- Parthenolide and Its Derivatives in the Treatment of Respiratory Tract Diseases: Therapeutic Effects and Molecular Mechanisms.Drug design, development and therapy · 2026Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
backgroundImproving the "cold" tumor immune microenvironment (TIME) of small-cell lung cancer (SCLC) represents a promising therapeutic approach. The metabolite lactate plays a crucial role in shaping the immune-cold tumor microenvironment (TME) and facilitating tumor progression. Phosphoglycerate kinase 1 (PGK1) is a key enzyme involved in tumor lactate metabolism. This study demonstrates that ACT001 improves the TIME of SCLC through inhibiting lactate production by targeting PGK1.
methodsThe cytotoxic effects of ACT001 on SCLC cell lines NCI-H1688 and NCI-H446 were evaluated using MTT assay, clone formation, EdU incorporation, wound healing, and invasion assays. To elucidate the mechanism of action of ACT001, proteomic techniques, pull-down assays, LC-MS/MS, surface plasmon resonance, immunofluorescence, lactate generation, glucose uptake, and western blot assays were conducted. A xenograft model was used to assess the in vivo anti-tumor activity of ACT001.
resultsACT001 inhibited the proliferation, invasion, and metastasis of SCLC both in vitro and in vivo. Additionally, it reduced lactate accumulation and M2 macrophage polarization. Mechanistically, ACT001 released micheliolide, which covalently modified Cys316 of PGK1 under physiological conditions. This suppressed PGK1 activity and restored the distribution of PGK1 in mitochondria and the cytoplasm under hypoxic conditions.
conclusionsACT001 inhibits the malignant progression of SCLC by suppressing lactate production, modulating macrophage polarization, and restraining tumor metastasis through PGK1 targeting.
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