ArticleNature chemical biology2022
Targeting colorectal cancer with small-molecule inhibitors of ALDH1B1.
Article in Nature chemical biology, 2022. 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 37 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- ALDH1B1 promotes mitochondrial γ-butyrobetaine biosynthesis and fatty acid oxidation in colorectal cancer.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial vulnerability to aldehydic load and the role mitochondrial aldehyde dehydrogenases.Pharmacological research · 2026Review
- Common human ALDH1B1 and ALDH2 variants increase neuroinflammatory response to a single ethanol dose in mice.Science advances · 2026Article
- Multimodal interpretable deep learning for transcriptome-informed precision oncology and drug mechanism analysis.NPJ digital medicine · 2026Article
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
- Flexible protein-ligand docking with diffusion-based side-chain packing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Compression-induced NF-κB activation sustains tumor cell survival in confinement by detoxifying aldehydes and promotes metastasis.Nature communications · 2025Article
- Development of retinoid nuclear receptor pathway antagonists through targeting aldehyde dehydrogenase 1A3.iScience · 2025Article
- Recent updates and future perspectives about ALDH1B1 as a potential anticancer target: a review.Journal of cancer research and clinical oncology · 2025Review
- ALDH1A1 promotes colorectal cancer metastasis through activating the notch signaling pathway.Medical oncology (Northwood, London, England) · 2025Article
- Mitochondrial ribosomal protein L3 (MRPL3): An early diagnostic biomarker and potential molecular target in pancreatic cancer.Translational oncology · 2025Article
- Metabolism-related ALDH1B1 acts as potential predictor and therapeutic target for primary gastrointestinal diffuse large B-cell lymphoma.Apoptosis : an international journal on programmed cell death · 2025Article
- Study on Tumor Budding and Immunoexpression of Cancer Stem Cell Marker ALDH1 in Oral Squamous Cell Carcinoma.Cureus · 2025Article
- SurfDock is a surface-informed diffusion generative model for reliable and accurate protein-ligand complex prediction.Nature methods · 2025Article
- Identification and validation of glucose metabolism-related gene signature in endometrial cancer.BMC cancer · 2025Article
- Multiple roles of ALDH1 in health and disease.Frontiers in physiology · 2025Review
- Mechanism of action and therapeutic value of anoctamin-1 in gastrointestinal cancers.Frontiers in immunology · 2025Review
- The Significance of Aldehyde Dehydrogenase 1 in Cancers.International journal of molecular sciences · 2024Review
- Identifying compound-protein interactions with knowledge graph embedding of perturbation transcriptomics.Cell genomics · 2024Article
- Exploring the Role and Pathophysiological Significance of Aldehyde Dehydrogenase 1B1 (ALDH1B1) in Human Lung Adenocarcinoma.International journal of molecular sciences · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Aldehyde dehydrogenases (ALDHs) are promising cancer drug targets, as certain isoforms are required for the survival of stem-like tumor cells. We have discovered selective inhibitors of ALDH1B1, a mitochondrial enzyme that promotes colorectal and pancreatic cancer. We describe bicyclic imidazoliums and guanidines that target the ALDH1B1 active site with comparable molecular interactions and potencies. Both pharmacophores abrogate ALDH1B1 function in cells; however, the guanidines circumvent an off-target mitochondrial toxicity exhibited by the imidazoliums. Our lead isoform-selective guanidinyl antagonists of ALDHs exhibit proteome-wide target specificity, and they selectively block the growth of colon cancer spheroids and organoids. Finally, we have used genetic and chemical perturbations to elucidate the ALDH1B1-dependent transcriptome, which includes genes that regulate mitochondrial metabolism and ribosomal function. Our findings support an essential role for ALDH1B1 in colorectal cancer, provide molecular probes for studying ALDH1B1 functions and yield leads for developing ALDH1B1-targeting therapies.
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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.