1 ized that these lymphocytes would respond to
forodesine.
2 LL lymphocytes with 10 or 20 microM dGuo and
forodesine (
2 microM) resulted in accumulation of higher
3 h progressive disease were eligible for oral
forodesine (
200 mg/d) for up to 24 weeks.
4 were treated with an intravenous infusion of
forodesine (
40 mg/m2) on day 1; treatment continued on d
5 Median peak level of
forodesine (
5.4 microM) was achieved at the end of infus
6 e-based synthesis of immucillin-H (BCX-1777,
forodesine),
a transition-state analog of PNP.
7 Forodesine,
a potent inhibitor of PNP, was designed base
8 Forodesine,
a purine nucleoside phosphorylase inhibitor,
9 onversely, MSC viability was not affected by
forodesine and dGuo.
10 rom 12 patients with CLL were incubated with
forodesine and dGuo.
11 ical mechanism for MSC-derived resistance to
forodesine and emphasizes the need to move toward combin
12 d on these data, a phase 2 clinical trial of
forodesine has been initiated for CLL patients.
13 Forodesine has biologic activity in CLL; pharmacodynamic
14 Initial clinical data indicate
forodesine has significant activity on circulating CLL c
15 odynamic effectiveness of the PNP inhibitor,
forodesine;
however, regrowth of leukemia cells in the b
16 fere with the purine metabolic pathway (e.g.
forodesine),
immunomodulatory agents, proapoptotic small
17 A phase 1 clinical trial of
forodesine in T-cell malignancies demonstrated significa
18 al studies provided the rationale for use of
forodesine in T-cell malignancies.
19 Previous studies established that
forodesine in the presence of deoxyguanosine (dGuo) inhi
20 We demonstrate that spontaneous and
forodesine-
induced apoptosis of CLL cells was significan
21 MSC-induced biochemical changes antagonized
forodesine-
induced CLL cell apoptosis.
22 the impact of marrow stromal cells (MSCs) on
forodesine-
induced response in CLL lymphocytes.
23 Also, MSCs rescued CLL cells from
forodesine-
induced RNA- and protein-synthesis inhibition
24 Forodesine is a new and potent purine nucleoside phospho
25 Forodesine-
promoted dGuo triphosphate (dGTP) accumulatio
26 Steady-state level of
forodesine ranged from 200 to 1300 nM and did not reach
27 /m2) on day 1; treatment continued on day 2;
forodesine was administered every 12 hours for an additi