[Conjugation to Branched Glycerol Oligomers, a Novel Strategy for Extremely Hydrophobic Agents].

[Conjugation to Branched Glycerol Oligomers, a Novel Strategy for Extremely Hydrophobic Agents]. Yakugaku Zasshi. 2020;140(8):1001-1006 Authors: Miyamoto L, Abe S, Nemoto H, Tsuchiya K Abstract Ascertaining the absorption, distribution, metabolism, and excretion (ADME) profile of drugs is one of the most crucial factors in the process of drug discovery. Since it is important to combine water solubility and cell permeability within the compound to achieve the desired ADME properties, an appropriate balance between lipophilicity and hydrophilicity is required. It is often necessary to facilitate hydrophilicity of very hydrophobic candidates, because quite lipophobic molecules are rarely hit as positive in molecular-targeted or cell-based screenings. For that purpose, it has been popular to conjugate hydrophobic molecules with polyethylene glycol (PEG). However, PEG is a polymer, and PEG-conjugated molecules are not uniform. Besides, the dosage should be much increased compared with the original molecule due to the increase in molecular weight. Therefore we have been developing alternative ways to endow hydrophobic compounds with extra hydrophilicity by conjugating with symmetrically branched glycerol oligomers. This technology is versatile and easily applicable to various hydrophobic compounds. Water-solubility of fenofibrate, one of the most hydrophobic medicines in clinical use, was facilitated by a factor of more than 2000, and its ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research