leucettine L41

Leucettine L41 is a synthetic small molecule analogue of the marine sponge alkaloid Leucettamine B, developed by ManRos Therapeutics. It serves as a potent inhibitor of Dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) and CDC-like kinases (CLKs). In the context of Alzheimer's disease (AD), Leucettine L41 has been identified for its unique ability to prevent the calpain-mediated proteolytic cleavage of DYRK1A into truncated forms (DYRK1AT). These truncated forms accumulate in astrocytes and exhibit an increased affinity for STAT3α, a key regulator of neuroinflammation. By inhibiting this proteolysis and maintaining full-length DYRK1A, Leucettine L41 reduces the phosphorylation of STAT3α and the subsequent release of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-12). Preclinical studies in APP/PS1 mouse models demonstrate that treatment with Leucettine L41 promotes microglial recruitment to amyloid plaques, reduces amyloid-β burden, restores synaptic plasticity, and rescues memory functions.

Other names

L41L-41L 41