5'-S-(3-Aminophenyl)-5'-thioadenosine, a Novel Chemoprotective Agent for Reducing Toxic Side Effects of Fluorouracil in Treatment of MTAP-Deficient Cancers.

ABSTRACT: Nucleobase analogue (NBA) drugs, such as 5-fluorouracil (5-FU), are effective chemotherapeutics, but their clinical use is limited by severe side effects. Compelling evidence suggests that the use of S-methyl-5'-thioadenosine (MTA) can selectively reduce NBA toxicity on normal tissues while maintaining the efficacy of NBAs on methylthioadenosine phosphorylase (MTAP)-deficient cancers. However, we found that MTA induced hypothermia at its effective dose, limiting its translational potential. We hypothesized that an MTA analogue can retain the protective function of MTA without undesired side effects. We screened a library of MTA analogues and identified 5'-S-(3-aminophenyl)-5'-thioadenosine (m-APTA) as a substrate of MTAP that could be converted to adenine, a necessary step for protection o

SUBMITTER: Zhang S 

PROVIDER: S-EPMC12221788 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature