UCLA researchers have developed a potent and stable small molecule inhibitor of the ghrelin O-acyl transferase as potential therapy for obesity and type II diabetes.
BACKGROUND:
Obesity, and type II diabetes (T2D) resultant from obesity affect millions of people worldwide, and has reached epidemic level in society. Numerous means to counter the trend are being explored, which include lifestyle changes, bariatric surgeries, and pharmaceuticals. Several anti-diabetic drugs have been developed, but have shown undesired off-target effects involving receptor systems in the brain and have routinely failed to meet safety and/or efficacy standards. There is need for safe and potent anti-diabetic drugs in the marketplace.
INNOVATION:
UCLA researchers led by Prof. Patrick Harran developed novel inhibitors of the ghrelin O-acyl transferase (GOAT), an enzyme that plays an important role in obesity and diabetes. Inhibitors of GOAT can successfully restore insulin response to glucose challenge and thus can be used to treat type II diabetes and insulin resistance. The lead compound significantly reduced circulating acyl ghrelin levels when dosed in wild type mice. Data indicates the compound will be superior to competing molecules from Eli Lilly, Takeda, and Boehringer Ingelheim. In addition, this small molecule drug is a bench stable, crystalline solid that can be manufactured on scale using GMP protocols. Lastly, the inhibitor was designed to have pharmacological properties favorable for oral dosing.
POTENTIAL APPLICATIONS:
• Novel therapeutics for obesity and type II diabetes
ADVANTAGES:
• More efficacious than GOAT inhibitors described by Eli Lilly, Takeda, and Boehringer Ingelheim.
• Amenable to oral administration
• Stable, crystalline solid that is readily synthesized on scale
DEVELOPMENT-TO-DATE:
This invention has been tested in vivo in mice.