Concentrative uptake of melphalan, a cancer chemotherapeutic agent which is transported by the leucine-preferring carrier system.

The transport of melphalan, $\text{L}$-phenylalamine mustard, proceeded uphill against a concentration gradient and resulted in a distribution ratio of approximately 10. Concentrative uptake was temperature sensitive and was inhibited by the metabolic inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and $\text{L}$-leucine, a natural substrate of the transport carriers. These results indicate that melphalan transport is an energy requiring process and that naturally occurring competitive substrates such as leucine markedly reduce concentrative uptake of the drug.