%0 Journal Article
%T Development of a High
%A Ashwini K. Devkota
%A Eun Jeong Cho
%A Hou-Fu Guo
%A John R. Veloria
%A Jonathan M. Kurie
%A Kevin N. Dalby
%J SLAS DISCOVERY: Advancing Life Sciences R&D
%@ 2472-5560
%D 2019
%R 10.1177/2472555218817057
%X 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
%K lysyl hydroxylase-2 (LH2)
%K luminescence
%K high-throughput screen
%K succinate detection
%K cancer
%U https://journals.sagepub.com/doi/full/10.1177/2472555218817057