ArticleHaematologica2020
ASLAN003, a potent dihydroorotate dehydrogenase inhibitor for differentiation of acute myeloid leukemia.
Article in Haematologica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 78 citations in OpenAlex.
- DH-AUTAC induces ferroptosis in colorectal cancer by targeting DHODH for autophagic degradation through KCTD10-SQSTM1 signaling.Journal of gastroenterology · 2026Article
- Novel noscapine derivative induces AML differentiation by dual-engaging DHODH and mitochondrial lipids to trigger a metabolic-epigenetic-transcriptional cascade.Acta pharmaceutica Sinica. B · 2026Article
- Exploiting metabolic dependencies in acute myeloid leukemia: DHODH inhibition meets lipid and cholesterol metabolism.Haematologica · 2026Article
- Potent synergy of DHODH and SREBP inhibition in acute myeloid leukemia via disruption of cholesterol and lipid metabolism.Haematologica · 2026Article
- Roles of RRM2 and RRM2B in pyrimidine stress responses and differentiation of acute myeloid leukemia cells.Cell death discovery · 2026Article
- Antibody‒drug conjugates with DHODH inhibitor as novel payload class for cancer and SARS-CoV-2 infection therapies.Acta pharmaceutica Sinica. B · 2026Article
- BCOR mutations define a therapeutic vulnerability to DHODH Inhibition in acute myeloid leukemia.Annals of hematology · 2026Article
- Ferroptosis in AML: nanoparticles, biomarkers, and immune rewiring for therapeutic breakthroughs.Discover oncology · 2025Review
- PDE7A inhibition suppresses triple-negative breast cancer by attenuating de novo pyrimidine biosynthesis.Cell reports. Medicine · 2025Article
- Article
- Fluorescent Isostere (Journal of medicinal chemistry · 2025Article
- Pyrimidine metabolism reshapes immune microenvironment and implies poor prognosis in glioma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- DHODH modulates immune evasion of cancer cells via CDP-Choline dependent regulation of phospholipid metabolism and ferroptosis.Nature communications · 2025Article
- Bone marrow stromal cells enhance differentiation of acute myeloid leukemia induced by pyrimidine synthesis inhibitors.American journal of physiology. Cell physiology · 2024Article
- Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies.International journal of molecular sciences · 2024Review
- DHODH inhibition represents a therapeutic strategy and improves abiraterone treatment in castration-resistant prostate cancer.Oncogene · 2024Article
- Pyrimidine depletion enhances targeted and immune therapy combinations in acute myeloid leukemia.JCI insight · 2024Article
- Discovery of Alternative Binding Poses through Fragment-Based Identification of DHODH Inhibitors.ACS medicinal chemistry letters · 2024Article
- Unveiling novel insights in acute myeloid leukemia through single-cell RNA sequencing.Frontiers in oncology · 2024Review
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14 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Differentiation therapies achieve remarkable success in acute promyelocytic leukemia, a subtype of acute myeloid leukemia. However, excluding acute promyelocytic leukemia, clinical benefits of differentiation therapies are negligible in acute myeloid leukemia except for mutant isocitrate dehydrogenase 1/2. Dihydroorotate dehydrogenase catalyses the fourth step of the de novo pyrimidine synthesis pathway. ASLAN003 is a highly potent dihydroorotate dehydrogenase inhibitor that induces differentiation, as well as reduces cell proliferation and viability, of acute myeloid leukemia cell lines and primary acute myeloid leukemia blasts including in chemo-resistant cells. Apoptotic pathways are triggered by ASLAN003, and it also significantly inhibits protein synthesis and activates AP-1 transcription, contributing to its differentiation promoting capacity. Finally, ASLAN003 substantially reduces leukemic burden and prolongs survival in acute myeloid leukemia xenograft mice and acute myeloid leukemia patient-derived xenograft models. Notably, the drug has no evident effect on normal hematopoietic cells and exhibits excellent safety profiles in mice, even after a prolonged period of administration. Our results, therefore, suggest that ASLAN003 is an agent targeting dihydroorotate dehydrogenase with potential in the treatment of acute myeloid leukemia. ASLAN003 is currently being evaluated in phase 2a clinical trial in acute myeloid leukemia patients.
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