Lee, Yujeong; Onishi, Yoshiyuki; McPherson, Lisa; Kietrys, Anna M.; Hebenbrock, Marian; Jun, Yong Woong; Das, Ishani; Adimoolam, Shanthi; Ji, Debin; Mohsen, Michael G.; Ford, James M.; Kool, Eric T. published the artcile< Enhancing Repair of Oxidative DNA Damage with Small-Molecule Activators of MTH1>, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is human mutant homolog activator preparation oxidative DNA damage repair.
Here, it is reported that selected tyrosine kinase (TK) inhibitors including nilotinib, employed clin. in the treatment of chronic myeloid leukemia, are activators of the repair enzyme Human MutT Homolog 1 (MTH1). MTH1 cleanses the oxidatively damaged cellular nucleotide pool by hydrolyzing the oxidized nucleotide 8-oxo-2′-deoxyguanosine (8-oxo-dG)TP, which is a highly mutagenic lesion when incorporated into DNA. Structural optimization of analogs of TK inhibitors resulted in compounds such as SU0448, which induces 1000 +/- 100% activation of MTH1 at 10μM and 410 +/- 60% at 5μM. The compounds are found to increase the activity of the endogenous enzyme, and at least one (SU0448) decreases levels of 8-oxo-dG in cellular DNA. The results suggest the possibility of using MTH1 activators to decrease the frequency of mutagenic nucleotides entering DNA, which may be a promising strategy to suppress tumorigenesis in individuals with elevated cancer risks.
ACS Chemical Biology published new progress about DNA base excision repair. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate.
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