Leucovorin (LV)

Leucovorin, also known as folinic acid, is a 5-formyl derivative of tetrahydrofolic acid and a reduced form of the vitamin folic acid [1.1.1, 1.4.1]. It is not a biological target but a therapeutic agent used primarily as a "rescue" therapy to mitigate the toxic effects of dihydrofolate reductase (DHFR) inhibitors like methotrexate [1.1.1, 1.3.5]. By providing a source of reduced folate that bypasses the blocked DHFR enzyme, leucovorin allows for continued DNA and RNA synthesis in healthy cells [1.3.2, 1.3.4]. Additionally, leucovorin is used to enhance the cytotoxic activity of 5-fluorouracil (5-FU) in the treatment of colorectal and other cancers [1.2.3, 1.3.5]. It achieves this by stabilizing the ternary complex between the 5-FU metabolite FdUMP and the enzyme thymidylate synthase, leading to more effective inhibition of thymidine production [1.3.4, 1.4.2]. Leucovorin is also indicated for the treatment of megaloblastic anemia caused by folate deficiency when oral folic acid is not feasible [1.1.1, 1.2.3].

Other names

Folinic acidCitrovorum factor5-formyltetrahydrofolateCalcium folinateN5-formyl-tetrahydrofolate

Bypasses dihydrofolate reductase (DHFR) inhibition to provide reduced folates for nucleotide synthesis and stabilizes the binding of 5-fluorouracil metabolites to thymidylate synthase.