Hitchings G H
Drug Intell Clin Pharm. 1982 Nov;16(11):843-8. doi: 10.1177/106002808201601106.
A program in chemotherapy is described in which antimetabolites to constituents of nucleic acids were used as probes of enzymes and metabolic pathways. These studies led to a number of insights into nucleic acid biosynthesis and related biochemical fields. They also provided exploitable information that was developed into drugs for the treatment of leukemia, the prevention of rejection of organ transplants, and a new therapy for hyperuricemia and gout. Studies on infectious diseases provided insights into the modeling of inhibitor-enzyme complexes and led to new and effective antimicrobial and antiviral agents. Basic research and relative absences of specific targeting are shown to have greatly facilitated the progress of the program.
本文描述了一个化疗项目,其中将核酸成分的抗代谢物用作酶和代谢途径的探针。这些研究使人们对核酸生物合成及相关生物化学领域有了诸多深入了解。它们还提供了可利用的信息,这些信息被开发成用于治疗白血病、预防器官移植排斥反应以及治疗高尿酸血症和痛风的新疗法。对传染病的研究为抑制剂 - 酶复合物的建模提供了深入了解,并催生了新的有效抗菌和抗病毒药物。基础研究以及缺乏特定靶向性被证明极大地推动了该项目的进展。