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Pharmacological Inhibition of Stearoyl CoA Desaturase 1 in the Skin Induces Atrophy of the Sebaceous Glands

Meingassner, Josef and Aschauer, Heinrich and Winiski, Anthony and Dales, Natalie and Yowe, David and Winther, Michael and Zhang, Zahui and 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

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