ArticleSLAS discovery : advancing life sciences R & D2019
Development of a High-Throughput Lysyl Hydroxylase (LH) Assay and Identification of Small-Molecule Inhibitors against LH2.
Article in SLAS discovery : advancing life sciences R & D, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The trial behind it
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
15 citing papers in PubMed, 25 citations in OpenAlex.
- Extracellular Matrix Remodeling in Tumors: Forces Beyond Fibroblasts.Cancer research · 2026Article
- Recombinant Production and Characterization of Human Enzymes Responsible for Collagen Lysine Post-translational Modifications.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Lysyl hydroxylase 2 glucosylates collagen VI to drive lung cancer progression.The Journal of clinical investigation · 2025Article
- Harnessing the Biomimetic Effect of Macromolecular Crowding in the Cell-Derived Model of Clubfoot Fibrosis.Biomacromolecules · 2024Article
- An Active Site Tyr Residue Guides the Regioselectivity of Lysine Hydroxylation by Nonheme Iron Lysine-4-hydroxylase Enzymes through Proton-Coupled Electron Transfer.Journal of the American Chemical Society · 2024Article
- The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair.Bone research · 2024Article
- Review
- Unleashing the Potential of 1,3-Diketone Analogues as Selective LH2 Inhibitors.ACS medicinal chemistry letters · 2023Article
- Passing the post: roles of posttranslational modifications in the form and function of extracellular matrix.American journal of physiology. Cell physiology · 2023Review
- Computational Investigation of a Series of Small Molecules as Potential Compounds for Lysyl Hydroxylase-2 (LH2) Inhibition.Journal of chemical information and modeling · 2023Article
- Lysyl hydroxylase 2 deficiency promotes filopodia formation and fibroblast migration.Biochemical and biophysical research communications · 2022Article
- A FeFrontiers in molecular biosciences · 2022Article
- Lysyl hydroxylase 2-induced collagen cross-link switching promotes metastasis in head and neck squamous cell carcinomas.Neoplasia (New York, N.Y.) · 2021Article
- Fibrosis and cancer: A strained relationship.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- A hierarchical network of hypoxia-inducible factor and SMAD proteins governs procollagen lysyl hydroxylase 2 induction by hypoxia and transforming growth factor β1.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Lysyl hydroxylase-2 (LH2) catalyzes the hydroxylation of telopeptidyl lysine residues on collagen, leading to the formation of stable collagen cross-links that connect collagen molecules and stabilize the extracellular matrix. High levels of LH2 have been reported in the formation and stabilization of hydroxylysine aldehyde-derived collagen cross-links (HLCCs), leading to fibrosis and cancer metastasis in certain tissues. Identification of small-molecule inhibitors targeting LH2 activity requires a robust and suitable assay system, which is currently lacking. Thus, despite being a promising target for these diseases, small-molecule inhibitors for LH2 have yet to be reported. Therefore, we developed a luminescence-based strategy to monitor LH activity and validated its ability to identify new inhibitors in a screen of approximately 65,000 compounds against LH2. Primary hits were confirmed using the same LH assay against mimiviral L230. This newly developed LH assay is robust, suitable for high-throughput screening, and able to identify potent specific inhibitors of LH2.
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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.