ArticleACS medicinal chemistry letters2019
Discovery of Soft-Drug Topical Tool Modulators of Sphingosine-1-phosphate Receptor 1 (S1PR1).
Article in ACS medicinal chemistry letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The trial behind it
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Who cites it
4 citing papers in PubMed.
- Soft drugs: design principles and topical applications.Nature reviews. Drug discovery · 2026Review
- Targeting Intracellular Pathways in Atopic Dermatitis with Small Molecule Therapeutics.Current issues in molecular biology · 2025Review
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Corrections and comments
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Authors and funding
19 authors.
Funding
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Abstract
In order to study the role of S1PRs in inflammatory skin disease, S1PR modulators are dosed orally and topically in animal models of disease. The topical application of S1PR modulators in these models may, however, lead to systemic drug concentrations, which can complicate interpretation of the observed effects. We set out to design soft drug S1PR modulators as topical tool compounds to overcome this limitation. A fast follower approach starting from the drug ponesimod allowed the rapid development of an active phenolic series of soft drugs. The phenols were, however, chemically unstable. Protecting the phenol as an ester removed the instability and provided a compound that is converted by enzymatic hydrolysis in the skin to the phenolic soft drug species. In simple formulations, topical dosing of these S1PR modulators to mice led to micromolar skin concentrations but no detectable blood concentrations. These topical tools will allow researchers to investigate the role of S1PR in skin, without involvement of systemic S1PR biology.
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Registered trials
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