guanidine hydrazone

Guanidine hydrazone (specifically compound 2a, also known as meta-phenyl bis-guanylhydrazone) is a novel, blood-brain barrier (BBB)-permeable small molecule retromer stabilizer and pharmacological chaperone. It binds at the interface of vacuolar protein sorting 35 (VPS35) and vacuolar protein sorting 29 (VPS29), two key components of the cargo recognition core of the retromer complex. By stabilizing the retromer complex, guanidine hydrazone prevents its degradation, increases VPS35 levels, and enhances retromer-mediated endosomal cargo sorting and trafficking. This mechanism boosts cellular clearance pathways, including macroautophagy, chaperone-mediated autophagy, and the endosomal-lysosomal system, promoting the degradation of pathological protein aggregates such as alpha-synuclein and mutant SOD1. Guanidine hydrazone is under preclinical development as a potential disease-modifying neuroprotective treatment for neurodegenerative disorders, including Parkinson's disease and amyotrophic lateral sclerosis (ALS).

Other names

1,3-phenyl bis-guanyl hydrazone1,3-phenylenebis(guanylhydrazone)bis-1,3-phenyl guanylhydrazonemeta-phenyl bis-guanylhydrazonephenyl-1,3-bis-guanylhydrazone