Invention:
This invention is a new composition of matter spanning a 6,6-fused chemotype. The 6,6-analogs display strong inhibitory activity across protein kinases such as the DYRK family, including DYRK1A, DYRK2, and DYRK3, along with inhibiting CLK. The dual DYRK/CLK inhibitors have displayed activity in 3-D organoid models of glioblastoma. It is subsequently hypothesized that these inhibitors will have comparable activity in other solid tumors-origin cancers such as colorectal and castrate resistant prostate cancers.
Background:
Cells in signal information to each other via several different methods, one of which being phosphorylation. Enzymes known as kinases phosphorylate proteins, which in turn can modulate protein function, localization, half-life, or interactions with other proteins. Abnormal expression and/or activity of some of these kinases, DYRK1A in particular, is seen in many human nervous system diseases, such as cognitive deficits associated with Down syndrome, Alzheimer’s disease, tauopathies, dementia, Pick’s disease, Parkinson’s disease and other neurodegenerative diseases as well as some cancers. The technology being researched is a novel analog with inhibitory DYRK and CLK activity in organoid 3D systems, including glioblastoma cells lines.
Applications:
- Therapeutic potential
- Treatment for several diseases, including glioblastoma and colorectal cancer
Advantages:
- Novel composition of matter
- Efficiency demonstrated in glioblastoma cell lines and organoid 3D systems
- Utility spans the same therapeutic areas discussed in previous applications
