| Description | Clodronic acid disodium salt (Lodronate), a bisphosphonate, is a potent antiosteolytic agent which inhibits bone resorption. |
| In vitro | Clodronate显著降低了J774细胞培养物的整体存活率，EC50为300 μM，而用脂质体包裹的Clodronate则将J774细胞培养物的整体存活率的EC50降低到1 μM。Clodronate及其脂质体包裹形式都被代谢成一种不可水解的腺苷三磷酸（ATP）类似物，即腺苷5'-(β,γ-二氯亚甲基)三磷酸，可通过快速蛋白质液相色谱法在J774细胞提取物中检测到。[1] Clodronate诱导分离的破骨细胞凋亡。以脂质体形式给予的Clodronate也能诱导体外大鼠腹腔巨噬细胞和体内小鼠肝巨噬细胞的凋亡，但对于鼠巨噬细胞样RAW-264细胞则无效。[2] 经脂质体输送进入巨噬细胞的Clodronate会因细胞内积累和不可逆的代谢损伤而杀死这些细胞。[3] 包裹在脂质体中的Clodronate（clodrolip）有效清除了F9畸胎瘤和人A673横纹肌肉瘤小鼠肿瘤模型中的吞噬细胞，根据治疗和计划，显著抑制肿瘤生长，抑制率从75%到>92%不等。[4] Clodronate是一种不含氮的双膦酸盐，它不抑制蛋白质异戊烯化，但可以在细胞内代谢成β-γ-亚甲基（AppCp型）的ATP类似物，它对体外的巨噬细胞具有细胞毒性。Clodronate被代谢成AppCCl(2)p，而AppCCl(2)p通过一种涉及ADP/ATP转换酶竞争性抑制的机制，抑制线粒体氧消耗。[5] |
| Synonyms | Loron, Clodronate Disodium, 氯屈膦酸二钠, Lodronate |
| molecular weight | 288.86 |
| Molecular formula | CH4Cl2O6P0·2Na |
| CAS | 22560-50-5 |
| Storage | keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | H2O: 58.82 mg/mL (203.64 mM), Sonication is recommended. DMSO: Insoluble |
| References | 1. Frith JC, et al. J Bone Miner Res, 1997, 12(9), 1358-1367. 2. Selander KS, et al. Mol Pharmacol, 1996, 50(5), 1127-1138. 3. van Rooijen N, et al. J Immunol Methods, 1996, 193(1), 93-99. 4. Zeisberger SM, et al. Br J Cancer, 2006, 95(3), 272-281. 5. Lehenkari PP, et al. Mol Pharmacol, 2002, 61(5), 1255-1262. |