ArticleCell death & disease2022
Dihydroorotate dehydrogenase inhibition reveals metabolic vulnerability in chronic myeloid leukemia.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- Pre-diagnostic circulating untargeted metabolomics and risk of overall and clinically significant prostate cancer: a systematic review and meta-analysis.British journal of cancer · 2026Pooled it
- Combined inhibition of de novo pyrimidine synthesis and ATR promotes ATF4-mediated cell death inHemaSphere · 2026Article
- Targeting Mitochondrial Vulnerabilities in Chronic Myeloid Leukemia: From Pathobiology to Novel Therapeutic Opportunities.Cancers · 2026Review
- Fluorescent Isostere (Journal of medicinal chemistry · 2025Article
- Off-Target Inhibition of Human Dihydroorotate Dehydrogenase (ACS pharmacology & translational science · 2024Article
- The DHODH inhibitor teriflunomide impedes cell proliferation and enhances chemosensitivity to daunorubicin (DNR) in T-cell acute lymphoblastic leukemia.Annals of hematology · 2024Article
- NCellular and molecular life sciences : CMLS · 2024Review
- Puerarin alleviates oxaliplatin-induced neuropathic pain by promoting Nrf2/GPX4-mediated antioxidative response.PloS one · 2024Article
- Cloning and Characterization of YakAnimals : an open access journal from MDPI · 2023Article
Corrections and comments
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Authors and funding
26 authors at 13 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of different generations of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has led to the high overall survival of chronic myeloid leukemia (CML) patients. However, there are CML patients who show resistance to TKI therapy and are prone to progress to more advanced phases of the disease. So, implementing an alternative approach for targeting TKIs insensitive cells would be of the essence. Dihydroorotate dehydrogenase (DHODH) is an enzyme in the de novo pyrimidine biosynthesis pathway that is located in the inner membrane of mitochondria. Here, we found that CML cells are vulnerable to DHODH inhibition mediated by Meds433, a new and potent DHODH inhibitor recently developed by our group. Meds433 significantly activates the apoptotic pathway and leads to the reduction of amino acids and induction of huge metabolic stress in CML CD34+ cells. Altogether, our study shows that DHODH inhibition is a promising approach for targeting CML stem/progenitor cells and may help more patients discontinue the therapy.
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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.