Farnesyl diphosphate synthase (FDPS), a key enzyme in isoprenoid biosynthesis, catalyzes the conversion of isopentenyl pyrophosphate and dimethylallyl pyrophosphate to geranyl pyrophosphate and farnesyl pyrophosphate, which are protein prenylation substrates[3]. Alendronate, a nitrogen-containing bisphosphonate, is an inhibitor of farnesyl diphosphate synthase with IC50 of 460 nM, used for the treatment and prevention of osteoporosis[4]. Women with low femoral-neck bone mineral density received alendronate therapy (initially 5 mg daily, increased to 10 mg daily at 24 months) showed lower frequency of morphometric and clinical vertebral fractures[5]. Patients with osteoporosis received 5 and 10 mg of alendronate per day showed increased bone density of the lumbar spine by 2.1 ± 0.3 percent and 2.9 ± 0.3 percent, respectively, in comparison with placebo group[6]. Alendronate at 60 and 100 μM completely suppressed squalestatin 1-mediated CYP2B mRNA induction that effectively inhibited cellular farnesyl diphosphate synthase activity, and also partially suppressed phenobarbital-inducible CYP2B expression[7].
Alendronate sodium hydrate/阿仑膦酸钠 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Primary human skeletal muscle-derived progenitor cells (HSMPCs)
0.1-1μM
24 h
Alendronate significantly reversed dexamethasone-induced myotube atrophy and myogenic differentiation inhibition, and functioned through down-regulation of SIRT3 protein expression
Alendronate dose-dependently promoted the enlargement in diameters of myotubes and significantly inhibited dexamethasone-induced myotube atrophy and myogenic differentiation inhibition
To evaluate the cytotoxicity of CaALN-N on SKOV3-luc cells, results showed CaALN-N induced apoptosis via down-regulation of HER2 signaling pathway.
Adv Sci (Weinh). 2023 May;10(14):e2204654
Bone marrow osteoblastic cells
10 nM or 1 μM
21 days
Alendronate inhibited osteoblast differentiation, especially BSP gene expression
J Dent Res. 2012 Mar;91(3):268-74
Alendronate sodium hydrate/阿仑膦酸钠 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
ICR mice
Denervation-induced muscle atrophy and glycerol-induced muscle injury models
Oral administration
0.5 and 1 mg/kg
Continuous administration for 1 month until sacrifice at 7 days post-denervation or 5 days post-muscle injury
Low-dose alendronate by oral administration ameliorated muscular malfunction and morphological changes in mouse models of denervation-induced muscle atrophy and glycerol-induced muscle injury, functioning through negative regulation of SIRT3 expression
Alendronate indirectly inhibited osteoblast function through pre-osteoclasts, reducing bone formation
J Dent Res. 2012 Mar;91(3):268-74
Sprague-Dawley (SD) rats
Liquid nitrogen-treated femoral head necrosis model
Not specified
100 μM
10 days
Alendronate partially reversed the suppression of expression of BMP2, EIF2AK3, EIF2A, ATF4 caused by liquid nitrogen, potentially treating ONFH via targeting the BMP2/EIF2AK3/EIF2A/ATF4 pathway
搜索
