ArticleExperimental hematology & oncology2024
AOH1996 targets mitochondrial dynamics and metabolism in leukemic stem cells via mitochondrial PCNA inhibition.
Article in Experimental hematology & oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Review
- Screening for novel chemical scaffolds targeting PCNA identifies the Hsp90alpha inhibitor SNX-2112.Current research in structural biology · 2026Article
- Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer.Cancer research communications · 2026Article
- Allosteric inhibition of RAN decreases miR-126 biogenesis in endothelial cells and controls acute myeloid leukemia growth.Communications biology · 2026Article
- Identification and validation of lymphangiogenesis-related genes for predicting acute myeloid leukemia prognosis: insights from bulk RNA sequencing and single-cell RNA sequencing analyses.Clinical and experimental medicine · 2026Article
- JAK2V617F reprograms Hypoxia Inducible Factor-1 to induce a non-canonical hypoxia regulon in myeloproliferative neoplasms.Leukemia · 2026Article
- Chronic and non-canonical cGAS-STING activation: implications for health, disease, cancer, and emerging therapeutic opportunities.Apoptosis : an international journal on programmed cell death · 2026Review
- Senescence-related gene signature predicts prostate cancer progression and identifies PCNA as a therapeutic target via multi-omics machine learning integration.British journal of cancer · 2026Article
- AOH1996, an Inhibitor of PCNA, Sensitises Breast Cancer Cells to Cytotoxic Chemotherapy.Breast cancer (Dove Medical Press) · 2026Article
- The PCNA inhibitor AOH1996 impairs tumor growth and invasiveness in non-small cell lung cancer.Frontiers in pharmacology · 2026Article
- Correction: AOH1996 targets mitochondrial dynamics and metabolism in leukemic stem cells via mitochondrial PCNA inhibition.Experimental hematology & oncology · 2025Article
- Novel therapeutic strategies targeting resistance mechanisms in hematologic malignancies: from BCL2 inhibition to immunomodulatory approaches.Frontiers in pharmacology · 2025Review
- Metabolism and epigenetics in cancer: toward personalized treatment.Frontiers in endocrinology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
18 authors.
Funding
Abstract
Cytoplasmic proliferating cell nuclear antigen (PCNA) is highly expressed in acute myeloid leukemia (AML) cells, supporting oxidative metabolism and leukemia stem cell (LSC) growth. We report on AOH1996 (AOH), an oral compound targeting cancer-associated PCNA, which shows significant antileukemic activity. AOH inhibited growth in AML cell lines and primary CD34 + CD38 - blasts (LSC-enriched) in vitro while sparing normal hematopoietic stem cells (HSCs). In vivo, AOH-treated mice demonstrated prolonged survival compared to controls (50 vs. 35 days; p < 0.0001) with reduced LSC burden, as shown in secondary transplants (42 vs. 30 days, p < 0.0001). Mechanistically, AOH disrupted mitochondrial PCNA's binding to the OPA1 protein, enhancing OPA1's interaction with its E3 ligase, MARCH5, which led to OPA1 degradation. This process reduced mitochondrial length, fatty acid oxidation (FAO), and oxidative phosphorylation (OXPHOS), thereby inhibiting LSC expansion. The addition of venetoclax (VEN), an FDA-approved Bcl-2 inhibitor, further enhanced AOH's effects, reducing mitochondrial length, FAO, and OXPHOS while improving survival in AML models. While VEN is approved for AML, AOH is under clinical investigation for solid tumors, and our findings support its broader therapeutic potential.
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