Pharmacological Inhibition of Stearoyl CoA Desaturase 1 in the Skin Induces Atrophy of the Sebaceous Glands
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Meingassner, Josef, Aschauer, Heinrich, Winiski, Anthony, Dales, Natalie, Yowe, David, Winther, Michael, Zhang, Zahui, Stuetz, Anton and Billich, Andreas (2013) Pharmacological Inhibition of Stearoyl CoA Desaturase 1 in the Skin Induces Atrophy of the Sebaceous Glands. Journal of Investigative Dermatology, 133 (8). pp. 2091-2094. ISSN 0022-202X
Abstract
Stearoyl-CoA desaturase-1 (SCD-1) catalyzes the formation of delta9-monounsaturated fatty acids from saturated precursors. Deficiency of SCD-1 in mice causes atrophy of sebaceous glands. We asked whether local pharmacological inhibition of this enzyme in the skin would lead to a similar effect. To this end, we characterized the low-molecular-weight compound XEN103 as a potent and selective inhibitor of SCD-1 activity. The compound blocks microsomal and cellular SCD-1 activity across species with IC50 values in the range of 10-15 nM. Upon topical application to the skin of mice as a 1% solution, XEN103 induces pronounced sebaceous gland atrophy with a rapid onset after a few days of dosing, both sebaceous gland numbers and size being reduced by 50 to 75%, and without any signs of skin irritation. We show that the effect is due to the local action of the compound on SCD-1 in the skin and occurs in the presence of only minimal plasma exposure. Based on these observations, SCD-1 inhibitors such as XEN103 may provide an opportunity to develop a novel topical therapy for acne, as a disease characterized by overproduction of sebum from hypertrophic sebaceous glands.
| Item Type: | Article |
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| Keywords: | Stearoyl CoA Desaturase 1 Skin Sebaceous Gland |
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| Date Deposited: | 13 Oct 2015 13:14 |
| Last Modified: | 13 Oct 2015 13:14 |
| URI: | https://oak.novartis.com/id/eprint/8409 |