First thiazolamide PI4KIIIβ/HDAC dual inhibitors take a host-directed route against HCV
- Host-directed dual inhibition of PI4KIIIβ and HDACs had not previously been reported for hepatitis C, where resistance to direct-acting antivirals remains a concern.
- A series of thiazolamide-based dual inhibitors was designed, synthesised and evaluated.
- Lead compounds showed potent enzymatic inhibition of both targets together with anti-HCV activity.
💡 Points
With DAAs curing most patients, the case for a host-directed HCV drug is hard to make commercially, and a dual PI4KIIIβ/HDAC profile adds tox risk. I read this as a good exercise in multitarget design, but would want to see cytotoxicity and kinase selectivity before calling the window real.