AUTHOR=Kirsanov Kirill , Fetisov Timur , Antoshina Elena , Trukhanova Lubov , Gor’kova Tatiana , Vlasova Olga , Khitrovo Irina , Lesovaya Ekaterina , Kulbachevskaya Nataliya , Shcherbakova Tatiana , Belitsky Gennady , Yakubovskaya Marianna , Švedas Vytas , Nilov Dmitry TITLE=Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.842316 DOI=10.3389/fphar.2022.842316 ISSN=1663-9812 ABSTRACT=

7-Methylguanine (7-MG) competitively inhibits the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) and RNA-modifying enzyme tRNA-guanine transglycosylase (TGT) and represents a potential anticancer drug candidate. Furthermore, as a natural compound, it could escape the serious side effects characteristic for approved synthetic PARP inhibitors. Here we present a comprehensive study of toxicological and carcinogenic properties of 7-MG. It was demonstrated that 7-MG does not induce mutations or structural chromosomal abnormalities, and has no blastomogenic activity. A treatment regimen with 7-MG has been established in mice (50 mg/kg per os, 3 times per week), exerting no adverse effects or changes in morphology. Preliminary data on the 7-MG anticancer activity obtained on transplantable tumor models support our conclusions that 7-MG can become a promising new component of chemotherapy.