Forodesine (BCX-1777) is a highly potent and orally active purine nucleoside phosphorylase (PNP) inhibitor with IC₅₀ values ranging from 0.48 to 1.57 nM for human, mouse, rat, monkey and dog PNP. Forodesine is a potent human lymphocyte proliferation inhibitor. Forodesine could induce apoptosis in leukemic cells by increasing the dGTP levels^[1][2]. IC50 & Target: IC50: 1.19 nM (Human PNP), 0.48 nM (Mouse PNP), 1.24 nM (Rat PNP), 0.66 nM (Monkey PNP) and 1.57 nM (Dog PNP)^[2] In Vitro: Forodesine (10-30 μM; 24 and 48 hours; RPMI-8226, MOLT-4 and 5T33MM cells) treatment is partially inhibition of proliferation^[1].
Forodesine (10-30 μM; 24 and 48 hours; RPMI-8226, MOLT-4 and 5T33MM cells) has no effect on the MM cells at 24 hours, while it could reduce the percentage of living cells in the MOLT-4 cells with 40%^[1].
Forodesine (BCX-1777), in the presence of 2'-deoxyguanosine (dGuo, 3-10 μM), inhibits human lymphocyte proliferation activated by various agents such as interleukin-2 (IL-2), mixed lymphocyte reaction (MLR) and phytohemagglutinin (PHA) (IC50 values < 0.1-0.38 μM)^[2]. In Vivo: Forodesine (BCX-1777) has excellent oral bioavailability (63%) in mice^[2].
At a single dose of 10 mg/kg in mice, Forodesine elevates dGuo to approximately 5 μM^[2].
n the human peripheral blood lymphocyte severe combined immunodeficiency (hu-PBL-SCID) mouse model, Forodesine is effective in prolonging the life span 2-fold or more^[2].