From orexin receptor agonist YNT-185 to novel antagonists with drug-like properties for the treatment of insomnia.

YNT-185 is the first known small molecule acting as orexin 2 receptor (OXR) agonist with implication to narcolepsy treatment, served as a template scaffold in generating a small set of seven compounds with predictive affinity to OXR. The design of the new small molecules was driven mostly by improving physicochemical properties of the parent drug YNT-185 in parallel with in silico studies, later suggesting their favorable binding modes within the active site of OXR. We obtained seven new potential OXR binders that were evaluated in vitro for their CNS availability, cytotoxicity, and behavior pattern on OXR.

Albumin and α1-acid glycoprotein: old acquaintances.

Introduction: Albumin and α1-acid glycoprotein (AGP) are two of the most abundant proteins found in plasma. Their effect on the pharmacokinetic profile of exogenous compounds has major implications to clinical practice. Recent exploration into their possible role as diagnostic markers underlines their significance, and provides highlights their potential in medicinal applications.