SCIENCE
Molecular Target
The target of diazoxide choline is the ATP sensitive potassium channel, an octomeric complex comprising pore-forming (Kir6.x) and ATP binding (SUR, sulfonylurea receptor) components.
Different isotypes of the channel exist in key target tissues, e.g. SUR1 in pancreas, brain and adipose tissue; SUR2b in vasculature.
Activating SUR1 leads to triglyceride lowering, improved cholesterol profile and weight loss.
Activating SUR2b leads to blood pressure reductions.
These targets are validated by both human and animal models.
Chemistry
Diazoxide is a benzothiadiazine that is structurally related to the thiazide diuretics. In contrast to the thiazides, diazoxide lacks diuretic activity and functions as an activiator of the ATP sensitive potassium channel.
The choline salt of diazoxide significantly improves the solubility of diazoxide in aqueous solutions, contributing to improved bioavailability.
Efficient, scalable and high yield syntheses have been developed for diazoxide and diazoxide choline.
Polymorph control has been achieved and all of the non-clinical and clinical studies with diazoxide choline have been conducted with a stable and well-characterized polymorph.