Addressing the Metabolic Stability of Antituberculars through Machine Learning

We present the first prospective application of our mouse liver microsomal (MLM) stability Bayesian model. CD117, an antitubercular thienopyrimidine tool compound that suffers from metabolic instability (MLM t1/2 t1/2 values greater than or equal to 60 min. It is noteworthy that whole-cell efficacy and lack of relative mammalian cell cytotoxicity could not be predicted simultaneously. These results support the utility of our new MLM stability model in chemical tool and drug discovery optimization efforts.我们首次开展了自研小鼠肝微粒体（mouse liver microsomal, MLM）稳定性贝叶斯模型的前瞻性应用研究。CD117是一款抗结核噻吩并嘧啶类工具化合物，存在代谢不稳定性问题，其小鼠肝微粒体半衰期（MLM t1/2）值不低于60分钟。值得关注的是，我们无法同时预测该化合物的全细胞药效活性与相对哺乳动物细胞无细胞毒性这两项特性。上述结果证实了本新型MLM稳定性模型在化学工具化合物开发与药物发现优化工作中的应用价值。