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Topical 'dual-soft' glucocorticoid receptor agonist for dermatology.

Abstract：

:Steroidal glucocorticoids (GR agonists) have been widely used for the topical treatment of skin disorders, including atopic dermatitis. They are a very effective therapy, but they are associated with both unwanted local effects in the skin (skin thinning/atrophy) and systemic side effects. These effects can limit the long-term utility of potent steroids. Here we report on a topically delivered non-steroidal GR agonist, that has the potential to deliver high efficacy in the skin, but due to rapid metabolism in the blood & liver ("dual-soft") it should have greater systemic safety than existing treatments. In addition, compared to less selective steroidal GR agonists, the new non-steroidal Selective Glucocorticoid Agonists (SEGRAs) have the potential to avoid the skin atrophy observed with existing topical steroids. Due to its potential for reduced skin atrophy and low systemic exposure, LEO 134310 (17) may be suitable for long term topical treatment of skin diseases such as atopic dermatitis and psoriasis.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Dack KN,Johnson PS,Henriksson K,Eirefelt S,Carnerup MA,Stahlhut M,Ollerstam AK

doi

10.1016/j.bmcl.2020.127402

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

127402

issue

17

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(20)30513-8

journal_volume

30

pub_type

杂志文章

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