Na channels, disease, and related assays and compositions

US8816095B2 · kind B2 · utility

Assignee

• Georgetown University · US

Inventors

• Milton L. Brown · Brookeville, US
• Scott Grindrod · Rockville, US
• Thomas Walls · Glenside, US
• Todd M. Hansen · Grayslake, US
• Simeng Suy · Richmond, US
• Mikell Paige · Fairfax, US

Key dates

• Filing date: Aug 17, 2009
• Grant date: Aug 26, 2014
• Expiry date: Jun 18, 2030

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D317/26
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Disclosed are molecules and their synthesis, for use in blocking gated ion channels such as voltage-gated sodium channels (VGSCs) and prostate voltage sodium channels (PVSCs). These inhibitors have superior blocking efficacy, for instance in displacing the radioligand [3H]-Batrachotoxin-B ([3H]-BTX-B) that binds to site 2 of a VGSC. The molecules of the invention comprise a moiety which increases the binding affinity of molecules for the protein binding site in prostate cancer cells (PCs), and which is also fluorescent. In one embodiment the invention molecules are an inhibition system that can be used to target over-abundant or hyperactive VGSCs selectively in pain, epilepsy or prostate cancer, inhibiting the proliferation of PCs. The fluorescent moiety also facilitates screening, tracking, and pharmacodynamic studies of the drug in a biological system both in vitro and in vivo.