Neridronate
(Synonyms: 奈立膦酸) 目录号 : GC36723
An FPP synthase inhibitor
Cas No.:79778-41-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Neridronic acid is an amino bisphosphonate that inhibits farnesyl pyrophosphate (FPP) synthase (IC50 = 388.2 nM in a cell-free assay).1 It decreases the differentiation of RAW 264.7 cells into osteoclasts in a CRL-12257 co-culture model of osteoclastogenesis when used at concentrations ranging from 0.001 to 100 ?M.2 Neridronic acid (30 ?M) inhibits FGF2-induced proliferation and tube formation in human umbilical vein endothelial cells (HUVECs).3 It reduces the loss of trabeculae and increases bone density in the tibial metaphysis of growing rats when administered subcutaneously at a dose of 0.1 mg/kg per day.4
1.Dunford, J.E., Kwaasi, A.A., Rogers, M.J., et al.Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: Time-dependent inhibition of human farnesyl pyrophosphate synthaseJ. Med. Chem.51(7)2187-2195(2008) 2.Nicolin, V., Bareggi, R., Baldini, G., et al.Effects of neridronic acid on osteoclasts derived by physiological dual-cell culturesActa Histochem.109(5)397-402(2007) 3.Ribatti, D., Nico, B., Mangieri, D., et al.Neridronate inhibits angiogenesis in vitro and in vivoClin. Rheumatol.26(7)1094-1098(2007) 4.Schenk, R., Eggli, P., Fleisch, H., et al.Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the ratCalcif. Tissue Int.38(6)342-349(1986)
| Cas No. | 79778-41-9 | SDF | |
| 别名 | 奈立膦酸 | ||
| Canonical SMILES | OC(P(O)(O)=O)(CCCCCN)P(O)(O)=O | ||
| 分子式 | C6H17NO7P2 | 分子量 | 277.15 |
| 溶解度 | Water: 18.75 mg/mL (67.65 mM) | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.6082 mL | 18.0408 mL | 36.0815 mL |
| 5 mM | 0.7216 mL | 3.6082 mL | 7.2163 mL |
| 10 mM | 0.3608 mL | 1.8041 mL | 3.6082 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
The Rationale for Using Neridronate in Musculoskeletal Disorders: From Metabolic Bone Diseases to Musculoskeletal Pain
Int J Mol Sci 2022 Jun 22;23(13):6921.PMID:35805927DOI:10.3390/ijms23136921.
Neridronate or ((6-amino-1-hydroxy-1-phosphonohexyl) phosphonic acid) is an amino-bisphosphonate (BP) synthetized in Italy in 1986. Bisphosphonates are molecules with a P-C-P bond in their structure that allows strong and selectively binding to hydroxyapatite (HAP) as well as osteoclasts inhibition through different mechanisms of action. Neridronate was initially used to treat Paget disease of the bone, demonstrating effectiveness in reducing bone turnover markers as well as pain. The interesting molecular properties of Neridronate foster its wide use in several other conditions, such as osteogenesis imperfecta, and osteoporosis. Thanks to the unique safety and efficacy profile, Neridronate has been used in secondary osteoporosis due to genetic, rheumatic, and oncological diseases, including in pediatric patients. In the last decade, this drug has also been studied in chronic musculoskeletal pain conditions, such as algodystrophy, demonstrating effectiveness in improving extraskeletal outcomes. This review highlights historical and clinical insights about the use of Neridronate for metabolic bone disorders and musculoskeletal pain conditions.
Neridronate for transient osteoporosis of the hip in a child
Osteoporos Int 2022 Jul;33(7):1619-1624.PMID:35106625DOI:10.1007/s00198-022-06324-y.
Transient osteoporosis of the hip (TOH) is usually reported in middle-aged men or during pregnancy as a benign self-limiting condition. Nevertheless, its impact on quality of life in terms of pain and disability is considerable. Also, it can lead to insufficiency fractures or, more rarely, evolve into osteonecrosis. This condition is anecdotally described in the pediatric age and very little is known about how it may affect the growing bone. We herein describe a case of TOH in a 10-year-old child treated at our pediatric rheumatology service and summarize the pediatric cases of TOH previously reported in literature. There are two points of interest in our case report, the first one being the unusual complication of TOH with a femoral physis fracture and the second the complete recovery after the off-label therapy with bisphosphonates. We suggest that interventional medical treatment could be considered in selected cases of juvenile TOH, to prevent any possible irreversible damage on the femoral physis. As far as we know, this is the first report of Neridronate employment in children affected by TOH.
Efficacy of intravenous Neridronate in transient osteoporosis of the hip
Clin Exp Rheumatol 2022 Sep;40(9):1681-1685.PMID:35084313DOI:10.55563/clinexprheumatol/vzknda.
Objectives: To evaluate the efficacy and safety of intravenous (iv) Neridronate in patients affected by transient osteoporosis of the hip (TOH). Methods: We retrospectively evaluated the clinical records of patients affected by TOH treated with iv Neridronate in our department. We treated patients with a value of visual analogue scale (VAS)-pain ≥ 80/100 mm at diagnosis, limited range of movement and magnetic resonance images (MRI) findings suggestive of TOH. The regimen used was: one iv infusion at day 0, 3, 6, 9 (100 mg for each infusion: total of 400 mg). This protocol was repeated in refractory cases. Recovery was defined as VAS-pain level ≤20/100. Concomitant use of analgesics was allowed. Paired Student t-test was used to assess VAS-pain change. Results: Five patients were male, 3 were female. Mean age was 54.5±2.12 years old. Mean body mass index was 26.57±2.22. Mean time to diagnosis, since the onset of the symptoms, was 75±21.21 days. Mean number of Neridronate infusions was 7.5±2.56. Mean time of recovery was 57±45.96 days. Mean VAS-pain at baseline was 84±2,24. Mean VAS-pain after treatment was significantly reduced (p<0.001) with a value of 12.12±6.46. None of the patients needed analgesics after treatment. No adverse event was reported. In 5 cases, post-treatment MRI showed complete bone marrow oedema resolution. Conclusions: Intravenous Neridronate is effective and safe in the treatment of TOH and its use may lead to a faster resolution of the disease.
Intramuscular Neridronate for the treatment of complex regional pain syndrome type 1: a randomized, double-blind, placebo-controlled study
Ther Adv Musculoskelet Dis 2021 Jun 11;13:1759720X211014020.PMID:34178124DOI:10.1177/1759720X211014020.
Background: Complex regional pain syndrome type-1 (CRPS-1) is a severely disabling painful disease challenging to treat. This multicenter, randomized, double-blind placebo-controlled trial examined the efficacy of intramuscular (i.m.) Neridronate in CRPS-1 patients. Methods: A total of 78 patients diagnosed with CRPS-1 (aged 59.5 ± 10.3, 66.7% female) were randomly assigned to 25 mg (i.m.) Neridronate (N = 41) given once daily for 16 consecutive days or placebo control (N = 37). Efficacy was assessed after 30 days using a visual analogue scale (VAS) pain score and the number of patients achieving ⩾50% reduction in VAS score. Change in clinical signs and symptoms, quality of life (QoL) using Short Form Health Survey (SF-36) and the McGill Pain Questionnaire were also assessed. Results: After 30 days, VAS score decreased significantly to a greater extent in neridronate-treated patients versus placebo (31.9 ± 23.3 mm versus 52.3 ± 27.8 mm, p = 0.0003). Furthermore, the proportion of patients achieving a VAS reduction of ⩾50% was greater in the Neridronate group (65.9% versus 29.7%, p = 0.0017). Clinical signs and symptoms were improved significantly in the Neridronate group versus placebo for edema (72.5% versus 79.9%, p = 0.03), pain during motion (70% versus 83.3%, p = 0.0009), allodynia (20% versus 63.3%, p = 0.0004), and hyperalgesia (20% versus 56.7%, p = 0.0023). Whereas no difference was observed for QoL measures using the SF-36 questionnaire, three of the four pain variables using the McGill Pain Questionnaire improved significantly in the Neridronate group. No serious drug-related adverse events were reported during the study. Conclusion: In patients with acute CRPS-1, i.m. injections of 25 mg Neridronate were associated with clinically relevant benefit compared with placebo controls. Trial registration: EU Clinical Trials Register: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001156-28.
Effectiveness of Neridronate in the Management of Bone Loss in Patients with Duchenne Muscular Dystrophy: Results from a Pilot Study
Adv Ther 2022 Jul;39(7):3308-3315.PMID:35614293DOI:10.1007/s12325-022-02179-1.
Introduction: Bone loss is a major issue in patients affected by Duchenne muscular dystrophy (DMD), a rare musculoskeletal disorder, particularly in those treated with glucocorticoids (GCs). We aimed to assess the effectiveness of Neridronate in terms of bone mineral density (BMD) changes in this population. Methods: We retrospectively reviewed the records of patients affected by DMD receiving GCs referred to our outpatient from 2015 to 2020. All patients were treated with an intramuscular (IM) injection of Neridronate (25 mg every month). Bone density was measured at the lumbar spine (LS; L1-L4 tract) using dual-energy x-ray absorptiometry (DXA) (GE Lunar), no more than 4 weeks before (T0) and after 1 year from Neridronate treatment (T1). Results: Eight boys with DMD were included with a mean age at diagnosis of 4.75 ± 2.81 years. Six of them were non-ambulant and two of them had previous low-trauma fractures (a distal femur fracture and a vertebral compression fracture, respectively). All patients were receiving deflazacort [median duration of therapy 11.5 years (interquartile range 2-25)]. At the DXA evaluation (T0), the mean L1-L4 BMD value was 0.716 ± 0.164 g/cm2. Six patients (75%) showed an L1-L4 Z-score height-adjusted of less than - 2. The mean age of Neridronate initiation was 18.87 ± 6.81 years. All patients were supplemented with calcium carbonate and vitamin D at baseline. After 12 months of treatment (T1), the mean L1-L4 BMD value was 0.685 ± 0.190 g/cm2. Seven patients (87.5%) showed an L1-L4 Z-score of less than - 2. Changes in LS BMD and Z-score were not significant between T0 and T1 in our cohort (p = 0.674 and p = 0.208, respectively) as well as among non-ambulant patients with DMD without previous fragility fractures. Conclusions: In this study, we reported for the first time that Neridronate may slow bone loss in GC-treated patients with DMD at 1-year follow-up.