Kidney calcification increases the risk of chronic kidney disease. However, to date, renal calcium phosphate crystallization, a main initiating and driving factor of kidney calcification, has not been explored as a drug target. Pre-clinical drug development is hampered by limited knowledge on the broad range of kidney calcification disorders, characterized by a multifactorial process of disease progression. In this work, we first established an calcification profiling platform to accelerate pre-clinical drug discovery. The image-based profiling assay allowed the rapid testing of several ionic stimuli and/or inhibitory molecules. We then leveraged a previously established library of inositol hexakisphosphate analogues to identify a renal calcium phosphate inhibitor. A lead compound showed and efficacy to prevent calcium phosphate-induced kidney damage. In conclusion, this work reports a renal calcium phosphate inhibitor that could efficiently reduce kidney damage and emphasizes the utility and translational value of the calcification platform.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737319 | PMC |
| http://dx.doi.org/10.1021/acsptsci.0c00153 | DOI Listing |
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