Example 13
Cynomologous monkeys have sebaceous glands very similar in size to those of human facial skin and at a depth from the skin surface approximating that of the human (˜500 [Figure (not displayed)]m). SCD-1 inhibitors are screened by dosing topically to the upper back of monkeys BID for up to 3 months. Sebum production is analyzed by various methods. SebuTape is used for timed sebum collection and extracted lipids are quantified. Skin biopsies are obtained and changes in sebaceous gland size and surface area are monitored by standard histological evaluation. In both the extracted lipids from SebuTape and the skin biopsies, SCD-1 inhibition is also quantified by measuring inhibition of the conversion of stearoyl-CoA (18:0) to oleoyl-CoA (18:1). Good biological activity in this model is indicated by substantial inhibition of the conversion of stearoyl-CoA (18:0) to oleoyl-CoA (18:1) and substantial reduction in sebaceous gland size and sebum-specific lipids such as wax esters.
