Pharm Profile: Melphalan

摘要

Melphalan (also known as L-PAM, L-phenylalanine mustard, and L-sarcolysin) is classified as an antitumor alkylating agent in the nitrogen mustard or bischloroethylamine family. Using nitrogen mustards as antineoplastic agents followed the discovery that victims of mustard gas poisoning in World War I frequently developed bone marrow toxicity in the form of leukopenia, Further investigation into the use of nitrogen mustard gas in chemical warfare led to the development of nitrogen mustard (mechlorethamine), in which an ethamine group substitutes for the sulfhydryl in mustard gas, Melphalan was designed to target metabolically active cells such as tumor cells by substituting an amino acid moiety (phenylalanine) for the ethyl group of mechlorethamine,thereby facilitating uptake of the alkylating agent by the malignant cell. Melphalan uptake by cells is mediated by a cellular transport system that is also responsible for transporting the amino acid leucine.