DGAT-1 Inhibitor Program


Overview and Profile

DiacylGlycerol Acyl Transferase-1 (DGAT-1) is a key enzyme involved in the formation of triglycerides and is highly expressed in human fat metabolism sites such as intestine, liver, and adipose. Dietary triglycerides cannot be absorbed directly in the gastrointestinal, or GI, tract and are broken down into free fatty acids and monoglycerol in the intestine by pancreatic lipase. Once absorbed, the free fatty acids and glycerol are reassembled into triglycerides at the site of absorption, called an enterocyte, and packaged into chylomicron particles to be transported in the lymphatic system to be used throughout the body. DGAT-1 is one of two enzymes that catalyze the steps of triglyceride biosynthesis from mono- or diacylglycerol and fatty acids, and is mainly distributed in the intestine, liver and adipose tissue.


DGAT-1 Mediates Absorption of Fats from the GI Tract

DGAT-1Inhibition of DGAT-1 in the enterocyte reduces post-prandial fat deposition; increases nutrient sensing, satiety.

Inhibition of the enzyme has shown to reduce fat storage in animal models and clinical trials, leading to reduction of body weight. However, non-selective systemic reduction of fat formation can lead to undesirable side effects demonstrated in DGAT-1 null mice. By introducing a unique chemical function group into the DGAT-1 inhibitors, Viking is developing a series of lead compounds that selectively inhibited DGAT-1 at enterocytes, the intestinal absorptive cells responsible for the absorption of dietary fat, and that demonstrated efficacy in animal models of dietary induced obesity.