ArticleLeukemia2019
The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.
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Who cites it
132 citing papers in PubMed, 239 citations in OpenAlex.
- DHODH is the key target of the KDM4 inhibitor QC6352 in glioblastoma stem cells.Nature chemical biology · 2026Article
- Unique fluoroalkyl substituents: is there life after CFChemical science · 2026Review
- 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
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- Mitochondrial metabolism determines chemotherapy sensitivity in colorectal cancer.Nature metabolism · 2026Article
- DHODH-Mediated Suppression of Ferroptosis Supports Radioresistance and Represents a Therapeutic Vulnerability in Lung Cancer.Cancer research · 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
- Nitrogen metabolism profiling reveals cell state-specific pyrimidine synthesis pathway choice.Nature metabolism · 2026Article
- DHODH inhibition suppresses cutaneous squamous cell carcinoma growth by the induction of differentiation through perturbation of the cellular redox balance.Cell death & disease · 2026Article
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Targeting de novo pyrimidine synthesis confers vulnerability to copper-mediated ATR inactivation in PARP inhibitor-resistant ovarian cancer.Nature communications · 2026Article
- Bioinformatics Identification and Functional Analysis of Key Genes of Nucleotide Metabolism in Oral Squamous Cell Carcinoma.Oral health & preventive dentistry · 2026Article
- Ferroptosis as a Novel Therapeutic Strategy to Overcome Multidrug Resistance in Colorectal Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Antibody‒drug conjugates with DHODH inhibitor as novel payload class for cancer and SARS-CoV-2 infection therapies.Acta pharmaceutica Sinica. B · 2026Article
- Metabolic Dependency on De Novo Pyrimidine Synthesis Is a Targetable Vulnerability in Platinum-Resistant Ovarian Cancer.Cancer research · 2026Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Reawakening Differentiation Therapy in Acute Myeloid Leukemia: A Comprehensive Review of ATRA-Based Combination Strategies.Current oncology (Toronto, Ont.) · 2026Review
- RL-MSVP: Reinforcement Learning and Multi-scale Validation Pipeline Investigating Azole-Fused Pyrimidines as PotentialACS omega · 2025Article
- Inducing ferroptosis to improve cancer therapy: a promising tool for enhancing immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
72 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is a devastating disease, with the majority of patients dying within a year of diagnosis. For patients with relapsed/refractory AML, the prognosis is particularly poor with currently available treatments. Although genetically heterogeneous, AML subtypes share a common differentiation arrest at hematopoietic progenitor stages. Overcoming this differentiation arrest has the potential to improve the long-term survival of patients, as is the case in acute promyelocytic leukemia (APL), which is characterized by a chromosomal translocation involving the retinoic acid receptor alpha gene. Treatment of APL with all-trans retinoic acid (ATRA) induces terminal differentiation and apoptosis of leukemic promyelocytes, resulting in cure rates of over 80%. Unfortunately, similarly efficacious differentiation therapies have, to date, been lacking outside of APL. Inhibition of dihydroorotate dehydrogenase (DHODH), a key enzyme in the de novo pyrimidine synthesis pathway, was recently reported to induce differentiation of diverse AML subtypes. In this report we describe the discovery and characterization of BAY 2402234 - a novel, potent, selective and orally bioavailable DHODH inhibitor that shows monotherapy efficacy and differentiation induction across multiple AML subtypes. Herein, we present the preclinical data that led to initiation of a phase I evaluation of this inhibitor in myeloid malignancies.
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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.