Kiriakidis et al. show that small molecule inhibitors of prolyl hydroxylase domain (PHD) enzymes, which were developed as treatment for renal anaemia through activation of hypoxia inducible factor, suppress the secretion of complement C1q in vitro and in mice. C1q requires prolyl 4 hydroxylation for activation and the researchers found that C1q is hydroxylated by collagen prolyl 4 hydroxylase (CP4H) and not by PHD enzymes. They posit that C1q levels are reduced by PHD inhibitors through an off-target effect, which is likely mediated by the inhibition of CP4H.
References
Kiriakidis, S. et al. Complement C1q is hydroxylated by collagen prolyl 4 hydroxylase and is sensitive to off-target inhibition by prolyl hydroxylase domain inhibitors that stabilize hypoxia-inducible factor. Kidney Int. http://dx.doi.org/10.1016/j.kint.2017.03.008 (2017)
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Wrighton, K. PHD inhibitors miss their mark. Nat Rev Nephrol 13, 384 (2017). https://doi.org/10.1038/nrneph.2017.75
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DOI: https://doi.org/10.1038/nrneph.2017.75