Folate-related targets

Folate-related targets refer to a collective group of enzymes, receptors, and transporters involved in the folate metabolic pathway, which is essential for one-carbon metabolism and the synthesis of DNA, RNA, and amino acids [1, 8]. Primary therapeutic targets in this category include enzymes such as dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS), as well as the folate receptor alpha (FOLR1) [11, 14]. These targets are central to oncology, where antifolate drugs like methotrexate and 5-fluorouracil inhibit nucleotide production to arrest the growth of rapidly dividing cancer cells [5, 6]. Furthermore, FOLR1 is highly overexpressed in specific malignancies, such as ovarian and lung cancers, making it a valuable target for antibody-drug conjugates like mirvetuximab soravtansine [11, 15]. Beyond cancer, these targets are utilized in treating autoimmune conditions and infectious diseases by exploiting differences between human and microbial folate metabolism [2, 5]. However, because folate is vital for normal cell function, therapies targeting these molecules often carry risks of significant side effects, including myelosuppression and gastrointestinal toxicity [5, 14]. Clinical management often involves monitoring biomarkers like FOLR1 expression or MTHFR polymorphisms to optimize efficacy and minimize toxicity [1, 15].

Other names

Folate pathway targetsFolate metabolic enzymesAntifolate targetsFolate receptors and transporters

Inhibition of folate-dependent enzymes such as dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS) to disrupt DNA synthesis; receptor-mediated delivery of cytotoxic payloads via folate receptors; and inhibition of microbial folate biosynthesis.