4-Thiazolidinone, 5-[[4-(acetyloxy)-3-methylphenyl]methylene]-3-(2-methylphenyl)-2-(propylimino)-, (2Z,5Z)-

Description

CAY10739 is a soft-drug agonist of the sphingosine-1-phosphate receptor 1 (S1P₁; IC₅₀ = 25.12 nM in a β-arrestin recruitment assay) that was designed to prevent systemic effects following topical application.¹ It is selective for S1P₁ over S1P₂, S1P₃, and S1P₄ (IC₅₀s = 1,000, >10,000, >10,000 nM, respectively, in a β-arrestin recruitment assay). In human S9 skin subcellular fractions, an ester group that protects an unstable phenol group is cleaved to release the active soft drug. The active soft drug and its nonenzymatically formed isomers are rapidly metabolized in isolated human hepatocytes.

References

1. Bell, M., Foley, D., Naylor, C., et al. Discovery of soft-drug topical tool modulators of sphingosine-1-phosphate receptor 1 (S1PR1) ACS Med. Chem. Lett. 10(3),341-347(2019).