In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells.

ABSTRACT:

Purpose

The alkylating agent melphalan prolongs survival in patients with multiple myeloma; however, it is associated with toxicities and development of drug-resistance. Here, we evaluated the efficacy of melphalan-flufenamide (mel-flufen), a novel dipeptide prodrug of melphalan in multiple myeloma.

Experimental design

Multiple myeloma cell lines, primary patient cells, and the human multiple myeloma xenograft animal model were used to study the antitumor activity of mel-flufen.

Results

Low doses of mel-flufen trigger more rapid and higher intracellular concentrations of melphalan in multiple myeloma cells than are achievable by free melphalan. Cytotoxicity analysis showed significantly lower IC50 of mel-flufen than melphalan in multiple myeloma cells. Importantly, me

SUBMITTER: Chauhan D 

PROVIDER: S-EPMC4098702 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature