Conversion of a PROTAC Mutant Huntingtin Degrader into Small-Molecule Hydrophobic Tags Focusing on Drug-like Properties was written by Hirai, Keigo;Yamashita, Hiroko;Tomoshige, Shusuke;Mishima, Yugo;Niwa, Tatsuya;Ohgane, Kenji;Ishii, Mayumi;Kanamitsu, Kayoko;Ikemi, Yui;Nakagawa, Shinsaku;Taguchi, Hideki;Sato, Shinichi;Hashimoto, Yuichi;Ishikawa, Minoru. And the article was included in ACS Medicinal Chemistry Letters in 2022.Related Products of 111-46-6 This article mentions the following:
The onset of neurodegenerative disorders (NDs), such as Alzheimer’s disease, is associated with the accumulation of aggregates of misfolded proteins. We previously showed that chem. knockdown of ND-related aggregation-prone proteins can be achieved by proteolysis targeting chimeras (PROTACs). However, hetero-bifunctional PROTACs generally show poor permeability into the central nervous system, where NDs are located. Here, we document the conversion of one of our PROTACs into hydrophobic tags (HyTs), another class of degraders bearing hydrophobic degrons. This conversion decreases the mol. weight and the number of hydrogen bond donors/acceptors. All the developed HyTs lowered the level of mutant huntingtin, an aggregation-prone protein, with potency comparable to that of the parent PROTAC. Through IAM chromatog. anal. and in vivo brain penetration assay of the HyTs, we discovered a brain-permeable HyT. Our results and mechanistic anal. indicate that conversion of protein degraders into HyTs could be a useful approach to improve their drug-like properties. In the experiment, the researchers used many compounds, for example, 2,2′-Oxybis(ethan-1-ol) (cas: 111-46-6Related Products of 111-46-6).
2,2′-Oxybis(ethan-1-ol) (cas: 111-46-6) belongs to alcohols. Alcohols are among the most common organic compounds. They are used as sweeteners and in making perfumes, are valuable intermediates in the synthesis of other compounds, and are among the most abundantly produced organic chemicals in industry. The most common reactions of alcohols can be classified as oxidation, dehydration, substitution, esterification, and reactions of alkoxides.Related Products of 111-46-6
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts