New Drugs for the Prevention of Kidney Stones

In vivo efficacy study of an LH prodrug expressed as days CaOx crystals were detected in mouse urine/mouse/week


Invention Summary:

Hyperoxaluria is a condition characterized by excessive urinary excretion of oxalate. It can result from inherited genetic mutations, intestinal diseases, or a diet high in oxalate. This often leads to calcium oxalate kidney stones. While surgery is necessary for severe cases and some rare primary hyperoxaluria from specific genetic mutations can be addressed with the recently available siRNAs, general management of most cases involves drinking a large amount of fluid and limiting oxalate-rich food.

Rutgers researchers have identified novel oxamates as potent inhibitors of calcium oxalate crystallization. These compounds, designed and synthesized in-house, were discovered using a crystallization inhibition assay developed at Rutgers. To enhance oral bioavailability, prodrugs were designed and synthesized. The resulting small molecules (LH series) exhibit potent inhibitory activity in vitro at low micromolar concentrations. Their prodrugs have demonstrated both oral bioavailability and efficacy in an animal model of hyperoxaluria. This discovery can lead to a new treatment to prevent kidney stones in patients with all types of hyperoxaluria, including the more common secondary hyperoxaluria.

Market Applications:

  • Effective oral therapy for the prevention of kidney stones in patients with all types of hyperoxaluria.

Advantages:

  • Small molecule therapy
  • Potent inhibitors of CaOx crystallization
  • Prodrugs with improved lipophilicity for better oral bioavailability
  • Works in patients with all types of hyperoxaluria

Publication: ACS Med. Chem. Lett. 2024  https://doi.org/10.1021/acsmedchemlett.4c00423

Intellectual Property & Development Status: Patent pending. Available for licensing and/or research collaboration. For any business development and other collaborative partnerships contact:  marketingbd@research.rutgers.edu

Patent Information: