leucettinib-21

Leucettinib-21 is a synthetic small molecule inhibitor of the dual-specificity, tyrosine phosphorylation-regulated kinase DYRK1A. It was developed through medicinal chemistry optimization of Leucettamine B, a natural product from the marine sponge Leucetta microraphis. The drug is designed to cross the blood-brain barrier and is administered orally in tablet form. By inhibiting DYRK1A, which is overactive in Alzheimer's disease and Down syndrome (trisomy 21), leucettinib-21 aims to correct cognitive deficits and improve memory and learning. Preclinical studies have shown that it can reduce pathology or improve cognition in rodent models of both diseases. The compound also inhibits related kinases such as DYRK1B, CLK1, and CLK4 at nanomolar concentrations but shows highest selectivity for DYRK1A. As of early 2024, leucettinib-21 has entered phase 1 clinical trials to assess safety and pharmacology in healthy volunteers as well as adults with Down syndrome or Alzheimer's disease[1][2][3][5][8].