Description
Forodesine is a purine nucleoside analog and purine nucleoside phosphorylase (PNP) inhibitor (IC50s = 1.19, 0.48, 1.24, 0.66, and 1.57 nM for human, mouse, rat, monkey, and dog PNP, respectively). It inhibits phytohemagglutinin A-, mixed lymphocyte reaction-, or IL-2-induced proliferation of isolated human peripheral blood lymphocytes (PBLs; IC50s = <0.1-0.38 μM) in the presence, but not absence, of 2’-deoxyguanosine (dGuo). Forodesine inhibits proliferation of CEM-SS T cell acute lymphoblastic leukemia (T-ALL) cells. In vivo, forodesine (10 mg/kg) prolongs survival in the hu-PBL-SCID mouse model of xenogeneic graft versus host disease (GVHD).