Inhibitors of Calcium Oxalate Crystallization for the Treatment of Oxalate Nephropathies

Abstract: Calcium oxalate (CaOx) crystal‐induced nephropathies comprise a range of kidney disorders, for which there are no efficient pharmacological treatments. Although CaOx crystallization inhibitors have been suggested as a therapeutic modality already decades ago, limited progress has been made in the discovery of potent molecules with efficacy in animal disease models. Herein, an image‐based machine learning approach to systematically screen chemically modified myo‐inositol hexakisphosphate (IP6) analogues is utilized, which enables the identification of a highly active divalent inositol phosphate molecule. To date, this is the first molecule shown to completely inhibit the crystallization process in the nanomolar range, reduce crystal–cell interactions, thereby preventing CaOx‐induced transcriptomic changes, and decrease renal CaOx deposition and kidney injury in a mouse model of hyperoxaluria. In conclusion, IP6 analogues based on such a scaffold may represent a new treatment option for CaOx nephropathies.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Inhibitors of Calcium Oxalate Crystallization for the Treatment of Oxalate Nephropathies ; volume:7 ; number:8 ; year:2020 ; extent:13
Advanced science ; 7, Heft 8 (2020) (gesamt 13)

Urheber
Kletzmayr, Anna
Mulay, Shrikant R.
Motrapu, Manga
Luo, Zhi
Anders, Hans‐Joachim
Ivarsson, Mattias E.
Leroux, Jean-Christophe

DOI
10.1002/advs.201903337
URN
urn:nbn:de:101:1-2022062613473243722860
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:34 MESZ

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Beteiligte

  • Kletzmayr, Anna
  • Mulay, Shrikant R.
  • Motrapu, Manga
  • Luo, Zhi
  • Anders, Hans‐Joachim
  • Ivarsson, Mattias E.
  • Leroux, Jean-Christophe

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