Heat shock proteins (Hsp) are produced by cells under conditions of internal or external stress and play a critical role in protein folding, aggregation, and degradation. Thus, maintenance of protein homeostasis is an important therapeutic goal in disorders such as Huntington disease (HD), which is caused by an abnormal form of the ubiquitous protein huntingtin. Hsp70 is a particularly critical member of the family of heat shock proteins that acts to inhibit aggregation of denatured proteins, prevent misfolding, and dispose damaged proteins. Modulation of Hsp70 activity by small molecule enhancers could have significant benefits in the treatment of HD and other neurodegenerative disorders, but at present, there are no Hsp70 agonists on the market or in clinical trials.
Description
Using iterative alkylations, saponifications, and coupling reactions, Dr. Wipf and his team were able to synthesize novel thiadiazines in which the core heterocycle could be selectively functionalized. Previous analogs of these thiadiazines have been shown to act as agonists of Hsp70 and help to reduce alpha-synuclein aggregation associated with neurodegenerative diseases. This unique method of preparing and functionalizing synthetic thiadiazines has the potential to lead to potent and effective drugs to combat Huntington disease and other devastating neurodegenerative disorders.
Applications
· Synthesizing novel bioactive compounds with selectively functionalized cores as a platform discovery technology
· Treating protein misfolding disorders such as Huntingdon disease and other neurodegenerative disorders, as well as cancer and viral infections
Advantages
· Platform for building bioactive compounds is versatile and diversifiable
· Targets an as-yet therapeutically unexplored family of proteins for treatment of neurodegenerative disorders
· Promising activity as both agonists and antagonists of Hsp70; the latter of which could have utility in treating cancer and infective diseases, including viral infections
Invention Readiness
In vitro data
IP Status
https://patents.google.com/patent/US20230131668A1
