Drug intelligence / Profile preview

pemetrexed + oxaliplatin + 5-fluorouracil + leucovorin

Development stage
Preclinical
Lead developer
Eli Lilly
Modality
Small Molecules
Administration
Intravenous
01

Overview

This is a combination chemotherapy regimen consisting of four agents: - **Pemetrexed** is a multi-targeted antifolate that inhibits several folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides, thereby interfering with DNA and RNA synthesis. - **Oxaliplatin** is a third-generation platinum-based chemotherapeutic agent that forms DNA crosslinks, inhibiting DNA replication and transcription, leading to cell death. It has demonstrated efficacy particularly in colorectal cancer and shows synergistic activity when combined with 5-fluorouracil. - **5-Fluorouracil (5-FU)** is an antimetabolite that inhibits thymidylate synthase, disrupting DNA synthesis and function. It also incorporates into RNA, further impairing cellular processes. - **Leucovorin (folinic acid)** enhances the binding of 5-FU to thymidylate synthase, increasing its cytotoxicity. This specific four-drug combination does not have a widely recognized unique regimen name or established use as a standard protocol; however, combinations involving oxaliplatin, 5-fluorouracil, and leucovorin (such as FOLFOX) are well-established for advanced colorectal cancer[1][2][3][5]. Pemetrexed has been studied in various regimens but not commonly combined with all three other agents simultaneously. The mechanism of action involves inhibition of nucleotide synthesis (pemetrexed/5-FU), enhancement of fluoropyrimidine activity (leucovorin), and induction of DNA damage via platinum-DNA adducts (oxaliplatin).

02

Targets

GART (GAR transformylase)ATIC (Aminoimidazole carboxamide ribonucleotide transformylase)TS (Thymidylate synthase)DHFR (Dihydrofolate reductase)DNA

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