Small molecule SUMOylation activators are novel neuroprotective agents.

Small molecule SUMOylation activators are novel neuroprotective agents.
Bioorg Med Chem Lett. 2017 Dec 13;:
Authors: Krajnak K, Dahl R
Abstract
Neuronal loss characterizes many of the most intractable nervous system diseases that deprive our ageing population of their quality of life. Neuroprotective pharmacological modalities are urgently needed to address this burgeoning population. Small ubiquitin-like modifier (SUMO) conjugation has been established as an endogenous neuroprotective response, and we have discovered several classes of small molecules that enhance SUMO conjugation. Herein we describe the hit to lead campaign that enabled the discovery of 3 diverse classes of drug-like SUMOylation activators. Optimized compounds were ultimately validated in cell-based models of neuronal loss and provide a foundation for establishing systemically active SUMO activators to treat degenerative diseases such as Parkinson's disease, Alzheimer's disease, and stroke.
PMID: 29269215 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry Letters - December 13, 2017 Category: Chemistry Authors: Krajnak K, Dahl R Tags: Bioorg Med Chem Lett Source Type: research