Lodoxamide 0.1% eye drops

Tyrosinase, a copper-dependent oxidase, plays a critical role in melanin biosynthesis and is a target in skin-whitening cosmetics. Conventional inhibitors like arbutin and kojic acid are widely used but suffer from cytotoxicity, instability, and inconsistent efficacy, highlighting the need for safer, more effective alternatives. In this study, two ligand-based machine learning models were developed: one to predict the biological activity of compounds and the other to estimate specific pIC50 values. These models were employed to screen potential tyrosinase inhibitors from natural product libraries and FDA-approved drug databases. Subsequently, the molecules identified through machine learning screening were subjected to more precise multi tyrosinase-like structures molecular docking to refine the selection. We identified three top-ranking inhibitors, rhodanine-3-propionic acid, lodoxamide, and cytidine 5′-(dihydrogen phosphate), with strong binding affinities mediated by metal ion coordination and π–π interactions at the enzyme’s active site. In vitro assays revealed that all three compounds exhibited higher inhibitory activity against mushroom tyrosinase compared to arbutin (IC50 = 38.37 mM), with rhodanine-3-propionic acid displaying the most potent inhibition (IC50 = 0.7349 mM). Furthermore, transdermal permeation experimental results confirmed that these compounds achieved markedly better skin permeability than commercial arbutin-based formulations, highlighting their potential as next-generation agents for inhibiting melanin production in cosmetic applications.

Abstract licence: CC BY-NC-ND

A previous pharmacogenomic analysis identified cromolyn, an anti-allergic drug, as an effective anti-fibrotic agent that acts on hepatocytes and stellate cells. Furthermore, cromolyn was shown to be a G protein-coupled receptor 35 (GPR35) agonist. However, it has not been studied whether anti-fibrotic effects are mediated by GPR35. Therefore, in this study, the role of GPR35 in hepatic fibrosis was investigated through the use of lodoxamide, another anti-allergic drug and a potent GPR35 agonist. Long-term treatment with carbon tetrachloride induced hepatic fibrosis, which was inhibited by treatment with lodoxamide. Furthermore, CID2745687, a specific GPR35 antagonist, reversed lodoxamide-mediated anti-fibrotic effects. In addition, lodoxamide treatment showed significant effects on the mRNA expression of collagen Iα1, collagen Iα2, and TGF-β1 in the extracellular matrix. However, a transforming growth factor α (TGF-α) shedding assay revealed lodoxamide not to be a potent agonist of mouse GPR35 in vitro. Therefore, these results showed anti-fibrotic effects of lodoxamide in mice and raise concerns how lodoxamide protects against liver fibrosis in vivo and whether GPR35 is involved in the action.

Abstract licence: CC BY-NC 4.0