Forodesine hydrochloride (BCX-1777 hydrochloride) is a highly potent and orally active purine nucleoside phosphorylase (PNP) inhibitor with IC 50 values ranging from 0.48 to 1.57 nM for human, mouse, rat, monkey and dog PNP . Forodesine hydrochloride is a potent human lymphocyte proliferation inhibitor. Forodesine hydrochloride could induce apoptosis in leukemic cells by increasing the dGTP levels
In Vitro
Forodesine (10-30 μM; 24 and 48 hours; RPMI-8226, MOLT-4 and 5T33MM cells) treatment is partially inhibition of proliferation. 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%. 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) (IC 50 values < 0.1-0.38 μM). MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: Human RPMI-8226, human MOLT-4 (T-ALL) cells, 5T33MM (Multiple myeloma, MM). Concentration: 10 μM, 20 μM, 30 μM Incubation Time: 24 and 48 hours Result: At the effects at 48 hours, a complete block in proliferation in the MOLT-4 cells and 15% reduction in the 5T33MM cells. Apoptosis AnalysisCell Line: Human RPMI-8226, human MOLT-4 (T-ALL) cells, 5T33MM (Multiple myeloma, MM). Concentration: 10 μM, 20 μM, 30 μM Incubation Time: 24 and 48 hours Result: A limited induction of apoptosis.
In Vivo
Forodesine (BCX-1777) has excellent oral bioavailability (63%) in mice. At a single dose of 10 mg/kg in mice, Forodesine elevates dGuo to approximately 5 μM. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Form:Solid
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)
