Billich, Andreas, Meingassner, Josef, Nussbaumer, Peter, Desrayaud, Sandrine, Lam, Charles, Winiski, Anthony and Schreiner, Erwin (2004) 6-[2-(adamantylidene)-hydroxybenzoxazole]-O-sulfamate, a steroid sulfatase inhibitor for the treatment of androgen- and estrogen-dependent diseases. The Journal of Steroid Biochemistry and Molecular Biology, 92 (1-2). pp. 29-37. ISSN 0960-0760

Abstract

Steroid sulfatase (STS) offers a new target for the treatment of steroid hormone-dependent diseases, such as breast and prostate cancer and androgen-dependent skin diseases. We here characterize a novel non-estrogenic inhibitor of the enzyme, namely 6-[2-(adamantylidene)-hydroxybenzoxazole]-O-sulfamate (AHBS), with special attention to its potential use in the treatment of acne. The compound blocks STS activity in homogenates of human skin with IC(50)=16 nM. Following a single oral dose (5 mg/kg) in rats, the compound blocks STS in the skin by 95% at 8 h, followed by recovery of activity over 5 days. Following topical application to the skin, both in vitro and in vivo, AHBS passes through the stratum corneum leading to inhibition of STS activity in the dermal compartment with rapid onset and long duration. Topical application of AHBS to Göttingen minipigs for a period of 2 weeks does not induce symptoms of ichthyosis as seen in STS-deficient human subjects, but leads to a reduction of sebum secretion to the skin surface. Based on these data, clinical studies with AHBS in acne patients are warranted, in order to verify the hypothesis on the importance of the sulfatase pathway in androgen-dependent skin diseases.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.jsbmb.2004.06.004
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	Steroid sulfatase; Sulfamate; In vivo inhibition; Acne; Breast cancer
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.jsbmb.2004.06.004
Date Deposited:	14 Dec 2009 13:55
Last Modified:	31 Jan 2013 01:08
URI:	https://oak.novartis.com/id/eprint/716