4H-Pyrrolo3,2-dpyrimidin-4-one, 7-(2S,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-2-pyrrolidinyl-1,5-dihydro-, monohydrochloride

Uses

Fodosine Hydrochloride is a 23-pM inhibitor of bovine purine nucleoside phosphorylase (PNP) specifically designed as a transition state mimic.

Uses

Treatment of T-Cell malignancies such as acute lymphoblastic leukemia (ALL) and cutaneous T-cell lymphoma.

Biological Activity

Forodesine (BCX-1777; ImmH; Immucillin-H) is an orally active, tight-binding (bovine/human PNP Ki = 23/72 pM) and highly potent purine nucleoside phosphorylase (PNP, PNPase) inhibtor (IC50 in nM = 0.48/mouse, 0.66/monkey, 1.19/human, 1.24/rat, 1.57/dog) th at mimics the PNP transition-state structure. Forodesine inhibits human T-cell proliferation stimulated by IL-2, MLR- and PHA in cultures (IC50 in the presence of 10 μM dGuo = 60, 50, and 387 nM, respectively) and shows in vivo efficacy in a xenogeneic graft vs. host disease model using hu-PBL SCID mice (20 mg/kg b.i.d. p.o.).