ArticleACS chemical biology2018
Chemoproteomics-Enabled Covalent Ligand Screening Reveals ALDH3A1 as a Lung Cancer Therapy Target.
Article in ACS chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Natural Compound Melatonin Suppresses Breast Cancer Development by Regulating Circadian Rhythm.Nutrients · 2025Article
- Association of ALDH3A1 expression with tumor differentiation, pathological stage, and nodal status in oral squamous cell carcinoma.Journal of Taibah University Medical Sciences · 2025Article
- Targeting aldehyde dehydrogenase ALDH3A1 increases ferroptosis vulnerability in squamous cancer.Oncogene · 2025Article
- Targeted Protein Localization by Covalent 14-3-3 Recruitment.Journal of the American Chemical Society · 2024Article
- Natural Product-Inspired Molecules for Covalent Inhibition of SHP2 Tyrosine Phosphatase.Tetrahedron · 2024Article
- Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.International journal of molecular sciences · 2024Review
- Chronic restraint stress promotes oral squamous cell carcinoma development by inhibiting ALDH3A1 via stress response hormone.BMC oral health · 2024Article
- Covalent 14-3-3 Molecular Glues and Heterobifunctional Molecules Against Nuclear Transcription Factors and Regulators.bioRxiv : the preprint server for biology · 2023Article
- Hypoxia-induced ALDH3A1 promotes the proliferation of non-small-cell lung cancer by regulating energy metabolism reprogramming.Cell death & disease · 2023Article
- Profiling Sulfur(VI) Fluorides as Reactive Functionalities for Chemical Biology Tools and Expansion of the Ligandable Proteome.ACS chemical biology · 2023Article
- Ligandability of E3 Ligases for Targeted Protein Degradation Applications.Biochemistry · 2023Review
- Deubiquitinase-targeting chimeras for targeted protein stabilization.Nature chemical biology · 2022Article
- 10 years into the resurgence of covalent drugs.Future medicinal chemistry · 2021Article
- ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma.Journal of Cancer · 2021Article
- Multiparameter Kinetic Analysis for Covalent Fragment Optimization by Using Quantitative Irreversible Tethering (qIT).Chembiochem : a European journal of chemical biology · 2020Article
- Heterogeneous adaptation of cysteine reactivity to a covalent oncometabolite.The Journal of biological chemistry · 2020Article
- Secretome-Based Screening in Target Discovery.SLAS discovery : advancing life sciences R & D · 2020Review
- ALDH3A1 acts as a prognostic biomarker and inhibits the epithelial mesenchymal transition of oral squamous cell carcinoma through IL-6/STAT3 signaling pathway.Journal of Cancer · 2020Article
- Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications.ACS chemical biology · 2019Article
- S-glycosylation-based cysteine profiling reveals regulation of glycolysis by itaconate.Nature chemical biology · 2019Article
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4 authors.
Funding
Abstract
Chemical genetics is a powerful approach for identifying therapeutically active small molecules, but identifying the mechanisms of action underlying hit compounds remains challenging. Chemoproteomic platforms have arisen to tackle this challenge and enable rapid mechanistic deconvolution of small-molecule screening hits. Here, we have screened a cysteine-reactive covalent ligand library to identify hit compounds that impair cell survival and proliferation in nonsmall cell lung carcinoma cells, but not in primary human bronchial epithelial cells. Through this screen, we identified a covalent ligand hit, DKM 3-42, which impaired both in situ and in vivo lung cancer pathogenicity. We used activity-based protein profiling to discover that the primary target of DKM 3-42 was the catalytic cysteine in aldehyde dehydrogenase 3A1 (ALDH3A1). We performed further chemoproteomics-enabled covalent ligand screening directly against ALDH3A1, and identified a more potent and selective lead covalent ligand, EN40, which inhibits ALDH3A1 activity and impairs lung cancer pathogenicity. We show here that ALDH3A1 represents a potentially novel therapeutic target for lung cancers that express ALDH3A1 and put forth two selective ALDH3A1 inhibitors. Overall, we show the utility of combining chemical genetics screening of covalent ligand libraries with chemoproteomic approaches to rapidly identify anticancer leads and targets.
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