Calcium phosphate nanocluster (CPNC)

Calcium phosphate nanoclusters are metastable, spherical assemblies of calcium and phosphate ions, typically 10 nm in diameter, that serve as the fundamental precursors to crystalline hydroxyapatite [1]. In physiological environments, these clusters are stabilized by proteins such as Fetuin-A to form calciprotein particles (CPPs), which are essential for managing mineral transport and preventing systemic calcification [2]. However, the dysregulation and aggregation of these nanoclusters are central to the pathogenesis of vascular calcification and chronic kidney disease-mineral and bone disorder (CKD-MBD) [3]. While not a traditional protein-based therapeutic target like a receptor or enzyme, these clusters are the physical-chemical entities targeted by crystallization inhibitors [4]. Drugs such as bisphosphonates and the novel agent SNF472 (myo-inositol hexaphosphate) bind to the surface of these nanoclusters to prevent their transition into mature, pathogenic crystals [5]. The stability of these clusters in serum, quantified by the T50 calcification propensity assay, is a clinically relevant biomarker for assessing cardiovascular risk in patients with renal impairment [6]. Citations: [1] Onat, B., et al. (2020). Chem. Rev.; [2] Jahnen-Dechent, W., et al. (2011). Nephrol. Dial. Transplant.; [3] Smith, E. R., et al. (2013). Kidney Int.; [4] Heiss, A., et al. (2003). J. Biol. Chem.; [5] Perelló, J., et al. (2018). Br. J. Clin. Pharmacol.; [6] Pasch, A., et al. (2012). J. Am. Soc. Nephrol.

Other names

Posner's clustersAmorphous calcium phosphate clustersCalciprotein particlesCPPs

Inhibition of hydroxyapatite crystallization and stabilization of amorphous mineral phases