Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, United States.
Department of Chemical Engineering, University of California, Davis, Davis, California 95616, United States.
J Chem Inf Model. 2024 Jul 8;64(13):5232-5241. doi: 10.1021/acs.jcim.4c00344. Epub 2024 Jun 14.
Discovered in the 1920s, cytochrome is a terminal oxidase that has received renewed attention as a drug target since its atomic structure was first determined in 2016. Only found in prokaryotes, we study it here as a drug target for (). Most previous drug discovery efforts toward cytochrome have involved analogues of the canonical substrate quinone, known as Aurachin D. Here, we report six new cytochrome inhibitor scaffolds determined from a computational screen and confirmed on target activity through testing. These scaffolds provide new avenues for lead optimization toward therapeutics.
细胞色素 c 是一种末端氧化酶，于 20 世纪 20 年代被发现，自 2016 年其原子结构首次被确定以来，它作为药物靶点重新引起了人们的关注。细胞色素 c 仅存在于原核生物中，我们在这里将其作为 () 的药物靶点进行研究。以前大多数针对细胞色素 c 的药物发现工作都涉及经典底物醌的类似物，称为 Aurachin D。在这里，我们报告了从计算筛选中确定的六个新的细胞色素 c 抑制剂支架，并通过 () 测试证实了其靶标活性。这些支架为开发 () 治疗药物的先导化合物优化提供了新途径。
