Enhanced anticancer effect of thymidylate synthase dimer disrupters by promoting intracellular accumulation.

ABSTRACT:

Introduction

Thymidylate synthase (TS) plays a crucial role in cellular growth, proliferation, DNA synthesis, and repair, thus gaining attention for targeted therapies in cancer. TS overexpression and the altered pharmacokinetics of anti-TS drugs are among the most prominent causes of cellular resistance. Decreased drug influx and/or efficient efflux result in reduced drug access to the intracellular targets.

Results

In this study, we have evaluated and demonstrated the increased cytotoxic efficacy of novel TS dimer disrupters (Ddis) in the presence of specific inhibitors of drug efflux protein pumps in ovarian and colon cancer cells, suggesting that these compounds are substrates of the cellular drug extruders. A second strategy adopted to favor intracellular accumulation w

SUBMITTER: Marverti G 

PROVIDER: S-EPMC11602703 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature