SPI-1477

**SPI-1477**, also designated **SPI-77**, is an experimental brain-penetrant small-molecule inhibitor of the SPT5-RNA polymerase II transcription-elongation complex being studied by researchers at the Weizmann Institute of Science for Huntington's disease. By disrupting SPT5-RNA polymerase II complex function, it selectively lowers mutant huntingtin messenger RNA and protein expression while sparing wild-type huntingtin expression in preclinical models. In BACHD mice, SPI-1477 reduced mutant huntingtin, improved mitochondrial and brain-derived neurotrophic factor abnormalities, and improved motor and anxiety-like phenotypes; systemic oral or subcutaneous administration delayed disease deterioration. It remains a preclinical research-stage candidate with no identified approved product or clinical development program. ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC10940305/))

Other names

Podophyllin derivative