Forodesine hydrochloride (BCX-1777 hydrochloride) 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 hydrochloride 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 hydrochloride (BCX-1777 hydrochloride) 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 hydrochloride is a potent human lymphocyte proliferation inhibitor. Forodesine hydrochloride 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) (IC50values< 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 | -20°C, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen) |
| 溶解性数据 | In Vitro: H2O : 100 mg/mL(330.35 mM;Need ultrasonic) DMSO : 10 mg/mL(33.03 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.3035 mL | 16.5175 mL | 33.0349 mL | | 5 mM | 0.6607 mL | 3.3035 mL | 6.6070 mL | | 10 mM | 0.3303 mL | 1.6517 mL | 3.3035 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (stored under nitrogen)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： PBS Solubility: 36.67 mg/mL (121.14 mM); Clear solution; Need ultrasonic 2. 请依序添加每种溶剂： 5% DMSO 40%PEG300 5%Tween-80 50% saline Solubility: ≥ 0.5 mg/mL (1.65 mM); Clear solution 3. 请依序添加每种溶剂： 5% DMSO 95% (20%SBE-β-CDin saline) Solubility: ≥ 0.5 mg/mL (1.65 mM); Clear solution
*以上所有助溶剂都可在本网站选购。 |
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