X-165

The effect of the Triton X series on the solubilization and enzyme activity of neurosteroid sulfatase (NSS) in the bovine midbrain was investigated. Triton X-100 and X165 stimulated NSS activity in the bovine midbrain, while Triton X-305 did not. This apparent activation was attributed to the action of the detergents, and not to the latency of the enzyme or the removal of some inhibitory substance from the microsomes. The maximum stimulation was obtained when the length of the polyoxyethylene chain of the detergent was 16.

An anal. of 156 published/clin. candidates from the Journal of Medicinal Chem. between 2018 and 2021 was conducted to identify lead generation strategies most frequently employed leading to drug candidates.As in a previous publication, the most frequent lead generation strategies resulting in clin. candidates were from known compounds (59%) followed by random screening approaches (21%).The remainder of the approaches included directed screening, fragment screening, DNA-encoded library screening (DEL), and virtual screening.An anal. of similarity was also conducted based on Tanimoto-MCS and revealed most clin. candidates were distant from their original hits; however, most shared a key pharmacophore that translated from hit-to-clin. candidate.An examination of frequency of oxygen, nitrogen, fluorine, chlorine, and sulfur incorporation in clin. candidates was also conducted.The three most similar and least similar hit-to-clin. pairs from random screening were examined to provide perspective on changes that occur that lead to successful clin. candidates.