Small molecule HSL inhibitor

Hormone sensitive lipase (HSL) is an intracellular lipase found in most tissues. The lipase, that exists in a long and a short form, is capable of hydrolysing a variety of esters. The long form of HSL is expressed in steroidogenic tissues like testis, where it converts cholesteryl esters to free cholesterol for steroid hormone production. The short form is expressed in adipose tissue where it in concert with two other lipase, adipose triglyceride lipase (ATGL) and monoacylglycerol lipase (MGL), is involved in the hydrolysis triacylglycerols to free fatty acids and (FFAs) and glycerol. The main substrate for HSL in adipose tissue is diacylglycerol. The activity of HSL is regulated by insulin – it is high when circulating insulin levels are low and vice versa.

NNC0076-0079 is classified as a so-called substrate inhibitor. The HSL inhibitor NNC0076-0079 blocks the activity of HSL by interfering with its active site in a non-covalently fashion – the activation of HSL is regained as the enzyme hydrolyses the ester bond of the inhibitor.