Forodesine (BCX-1777) 是一种高效的口服活性的嘌呤核苷磷酸化酶 (PNP) 抑制剂，对人，小鼠，大鼠，猴和狗PNP的IC50值在 0.48 至 1.57 nM 之间。Forodesine 是有效的人类淋巴细胞增殖抑制剂，可通过增加 dGTP 水平而诱导白血病细胞凋亡 (apoptosis)。
| 生物活性 | Forodesine (BCX-1777) is a highly potent and orally activepurine nucleoside phosphorylase (PNP)inhibitor withIC50values ranging from 0.48 to 1.57 nM forhuman, mouse, rat, monkey and dog PNP. Forodesine is a potent human lymphocyte proliferation inhibitor. Forodesine could induceapoptosisin 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] |
体外研究
(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].
Cell Proliferation Assay[1] | Cell 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 Analysis[1] | Cell 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. |
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体内研究
(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].
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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