prexasertib + pemetrexed

**Prexasertib + pemetrexed** is an experimental combination of two anticancer drugs: prexasertib, a small-molecule inhibitor of checkpoint kinase 1 (CHK1), and pemetrexed, an antifolate chemotherapeutic agent. Prexasertib works by inhibiting CHK1, a key regulator of cell cycle progression and DNA damage response, thereby promoting replication stress and mitotic catastrophe in tumor cells with impaired DNA repair pathways. Pemetrexed inhibits multiple folate-dependent enzymes involved in purine and pyrimidine synthesis, leading to inhibition of DNA and RNA synthesis and tumor cell death. The combination has been explored in early-phase clinical trials for advanced and/or metastatic cancer, but evaluation was halted at a very early stage due to dose-limiting toxicities and a lack of established maximum tolerated dose[1][3]. The combination is not approved for any indication and remains investigational.