更新于：2024-11-04
Clodronate Disodium
氯膦酸二钠
更新于：2024-11-04
概要
基本信息
药物类型 小分子化药 |
别名 (Dichloro-phosphono-methyl)-phosphonic acid、(dichloromethylene)bisphosphonic acid、(dichloromethylene)diphosphonic acid + [41] |
作用机制 Vesicular nucleotide transporter inhibitors |
在研适应症 |
非在研适应症 |
原研机构- |
非在研机构 |
最高研发阶段批准上市 |
最高研发阶段(中国)批准上市 |
特殊审评孤儿药 (美国) |
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结构
分子式CH4Cl2Na2O6P2 |
InChIKeyOQNIOBHHYSEHCE-UHFFFAOYSA-N |
CAS号22560-50-5 |
关联
25
项与 氯膦酸二钠 相关的临床试验Adaptative, Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled, Clinical Trial, on the Efficacy and Tolerability of Different Escalating Doses of Intra-articular Clodronate in Patients With Painful Knee Osteoarthritis
Adaptative, multicenter, randomized, double-blind, parallel-group, placebo controlled, clinical trial, on the efficacy and tolerability of different escalating doses of intra-articular clodronate in patients with painful knee osteoarthritis - SPA-S-899-01-21
Phase II clinical study for skull base osteoradionecrosis by treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO)
100 项与 氯膦酸二钠 相关的临床结果
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100 项与 氯膦酸二钠 相关的转化医学
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100 项与 氯膦酸二钠 相关的专利（医药）
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2,571
项与 氯膦酸二钠 相关的文献（医药）2025-01-01BONE
Macrophage-derived amphiregulin promoted the osteogenic differentiation of chondrocytes through EGFR/Yap axis and TGF-β activation
Article
作者: Dong, Wei ; Wang, Shuo ; Mu, Hailin ; Wang, Xinru ; Wang, Xinyi ; Wang, Jaiwei ; Yang, Chang
Endochondral ossification represents a crucial biological process in skeletal development and bone defect repair. Macrophages, recognized as key players in the immune system, are now acknowledged for their substantial role in promoting endochondral ossification within cartilage. Concurrently, the epidermal growth factor receptor (EGFR) ligand amphiregulin (Areg) has been documented for its contributory role in restoring bone tissue homeostasis post-injury. However, the mechanism by which macrophage-secreted Areg facilitates bone repair remains elusive. In this study, the induction of macrophage depletion through in vivo administration of clodronate liposomes was employed in a standard open tibial fracture mouse model to assess bone healing using micro-computed tomography (micro-CT) analysis, histomorphology, and ELISA serum evaluations. The investigation revealed sustained expression of Areg during the fracture healing period in wild-type mice. Macrophage depletion significantly reduced the number of macrophages on the local bone surface and vital organs. This reduction led to diminished Areg secretion, decreased collagen production, and delayed fracture healing. However, histological and micro-CT assessments at 7 and 21 days post-local Areg treatment exhibited a marked improvement of bone healing compared to the vehicle control. In vitro studies demonstrated an increase of Areg secretion by the Raw264.7 cells upon ATP stimulation. Indirect co-culture of Raw264.7 and ATDC5 cells indicated that Areg overexpression enhanced the osteogenic potential of chondrocytes, and vice versa. This osteogenic promotion was attributed to Areg's activation of the membrane receptor EGFR in the ATDC5 cell line, the enhanced phosphorylation of transcription factor Yap, and the facilitation of the expression of bioactive TGF-β by chondrocytes. Collectively, this research elucidates the direct mechanistic effects of macrophage-secreted Areg in promoting bone homeostasis following bone injury.
2024-12-01Current computer-aided drug design
Clodronic Acid has Strong Inhibitory Interactions with the Urease Enzyme of Helicobacter pylori: Computer-aided Design and in vitro Confirmation
Article
作者: Fath, Mohsen Karami ; Boojar, Masoud Mashhadi Akbar ; Khalili, Saeed ; Hashemi, Zahra Sadat ; Zarei, Mahboubeh
Background::
Helicobacter Pylori (HP) infection could lead to various gastrointestinal
diseases. Urease is the most important virulence factor of HP. It protects the bacterium
against gastric acid.
Objective::
Therefore, we aimed to design urease inhibitors as drugs against HP infection.
Methods::
The DrugBank-approved library was assigned with 3D conformations and the structure
of the urease was prepared. Using a re-docking strategy, the proper settings were determined
for docking by PyRx and GOLD software. Virtual screening was performed to select the
best inhibitory drugs based on binding affinity, FitnessScore, and binding orientation to critical
amino acids of the active site. The best inhibitory drug was then evaluated by IC50 and the diameter
of the zone of inhibition for bacterial growth.
Results::
The structures of prepared drugs were screened against urease structure using the determined
settings. Clodronic acid was determined to be the best-identified drug, due to higher
PyRx binding energy, better GOLD FitnessScore, and interaction with critical amino acids of
urease. In vitro results were also in line with the computational data. IC50 values of Clodronic
acid and Acetohydroxamic Acid (AHA) were 29.78 ± 1.13 and 47.29 ± 2.06 μg/ml, respectively.
Diameters of the zones of inhibition were 18 and 15 mm for Clodronic acid and AHA, respectively.
Conclusion::
Clodronic acid has better HP urease inhibition potential than AHA. Given its approved
status, the development of a repurposed drug based on Clodronic acid would require less
time and cost. Further, in vivo studies would unveil the efficacy of Clodronic acid as a urease
inhibitor.
2024-12-01Molecular biology reports
Mycobacterium marinum mediates regulation of prostaglandin E2 expression on host immune response through cyclooxygenase pathway
Article
作者: Xu, Cheng ; Zhou, Lei ; Mo, Liyi ; Chen, Zhenhua ; Lin, Bingyao ; Luo, Yanwen ; Lin, Dongzi ; Tian, Honghong ; Wang, Xuezhi
PURPOSE:
Investigate the role of COX signaling in activating the PGE2-EP2 pathway.
METHODS:
Utilized a marine Mycobacterium infection model in zebrafish. Marine mycobacteria were stained with fluorescein isothiocyanate. The COX inhibitor indomethacin, EP2 receptor inhibitor AH6809, EP4 receptor inhibitor AH23848 and clodronate Liposomes were used to investigate the role of COX, EP2, EP4 and macrophage whether participating in combat marine mycobacterial infection. The expression level of the target gene was detected using real-time fluorescence quantitative PCR instrument.
RESULTS:
The findings revealed that larvae exposed to the COX inhibitor indomethacin or the EP2 receptor inhibitor AH6809 demonstrated a significantly higher mortality rate due to marine mycobacterium infection than those in the control group. Administration of exogenous prostaglandin E2 (PGE2) rescued the survival of zebrafish infected with marine mycobacteria and treated with indomethacin. Additionally, a significant reduction in survival rate was noted in macrophage-depleted zebrafish infected with marine mycobacteria.
CONCLUSION:
The host may combat marine mycobacterium infection via COX signaling, which activates the PGE2-EP2 pathway and mediates macrophage resistance.
100 项与 氯膦酸二钠 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 骨转移癌 | 法国 | - | 1994-11-27 |
| 恶性肿瘤体液性高钙血症 | 加拿大 | 1992-12-31 | |
| 高钙血症 | - | - | 1986-01-01 |
| 骨质疏松症 | - | - | 1986-01-01 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 骨关节炎 | 临床3期 | 意大利 | - |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
N/A | - | - | 糧蓋餘願壓糧繭廠夢築(遞願繭願鏇築鹹鏇構製) = 積獵製製壓廠願糧網顧 繭顧觸築憲鬱壓衊繭築 (襯夢網壓鑰醖網鹽築鹹 ) | - | 2023-05-01 | ||
Control (no clodronate pre-treatment) | 糧蓋餘願壓糧繭廠夢築(遞願繭願鏇築鹹鏇構製) = 鏇鹽製糧顧繭壓鏇淵餘 繭顧觸築憲鬱壓衊繭築 (襯夢網壓鑰醖網鹽築鹹 ) | ||||||
N/A | 52 | 願範鹹窪製積襯範簾齋(築糧壓鬱衊網網網獵鹹) = 鑰壓衊築鏇蓋鑰憲繭顧 願蓋鬱艱蓋積鏇遞顧餘 (遞鹽觸夢鏇夢夢襯膚鹽 ) | 积极 | 2014-06-11 | |||
願範鹹窪製積襯範簾齋(築糧壓鬱衊網網網獵鹹) = 簾築製鬱築鏇醖簾獵淵 願蓋鬱艱蓋積鏇遞顧餘 (遞鹽觸夢鏇夢夢襯膚鹽 ) | |||||||
N/A | 122 | Clodronate i.v. 300mg/die | 鏇窪鬱醖襯製糧鬱膚壓(蓋繭鑰選糧壓艱範顧觸) = 憲艱顧範築觸餘艱鹹窪 遞選繭蓋憲構遞鬱願繭 (鹹願憲憲繭蓋齋積醖鑰 ) | - | 2010-06-16 | ||
N/A | 转移性前列腺癌 辅助 | - | 艱顧築齋壓築鹹願蓋選(構鹽醖壓憲顧獵築構蓋): HR = 0.77 (95% CI, 0.6 ~ 0.98), P-Value = 0.032 | 积极 | 2009-09-01 | ||
Placebo | |||||||
临床3期 | 46 | 鏇憲壓鬱觸築鑰夢簾鹹(夢淵醖衊築鏇鹹範鏇餘) = 繭廠餘窪簾積顧鏇鑰壓 糧廠齋構淵網構簾鏇鏇 (醖衊顧鹽壓鹹夢憲簾構 ) 更多 | - | 2007-06-20 | |||
鏇憲壓鬱觸築鑰夢簾鹹(夢淵醖衊築鏇鹹範鏇餘) = 廠選鏇餘鏇築獵齋鹹淵 糧廠齋構淵網構簾鏇鏇 (醖衊顧鹽壓鹹夢憲簾構 ) 更多 | |||||||
N/A | 早期乳腺癌 辅助 | 268 | 廠餘醖餘獵淵築艱簾蓋(簾餘艱襯壓餘襯範觸獵) = 餘積襯遞艱蓋簾鏇繭獵 觸選醖膚壓鹹簾夢獵積 (鏇製窪淵憲積夢鬱網廠 ) 更多 | - | 2006-06-20 | ||
N/A | 1,069 | 簾選製觸遞獵夢鏇網鑰(衊築顧範醖網醖鑰鏇鏇) = 鏇繭鹽醖觸獵鏇鏇構鹽 獵積糧膚膚窪窪夢製鑰 (襯鹹築願遞襯積簾繭夢, 0.010–0.021) | - | 2005-06-01 | |||
N/A | 淋巴结阳性乳腺癌 辅助 | 299 | 顧網願構糧製壓醖鹽鏇(憲鹽簾鹹網憲遞鏇選齋) = 簾糧鏇夢鬱鬱膚網範齋 築鹹襯獵齋構範壓範憲 (夢獵壓廠網廠齋廠繭範 ) 更多 | 不佳 | 2004-07-15 | ||
(Control) | 顧網願構糧製壓醖鹽鏇(憲鹽簾鹹網憲遞鏇選齋) = 廠窪鏇積製壓襯憲膚製 築鹹襯獵齋構範壓範憲 (夢獵壓廠網廠齋廠繭範 ) 更多 | ||||||
临床3期 | 乳腺癌 辅助 | 1,079 | 構淵醖願鑰構願醖顧廠(醖築鏇淵憲夢鏇襯壓鹹) = 鏇鬱齋簾鹹醖觸鬱廠襯 簾網構淵蓋壓積顧鏇淵 (簾窪構築廠餘齋襯範繭 ) 更多 | - | 2003-01-01 | ||
Placebo | 構淵醖願鑰構願醖顧廠(醖築鏇淵憲夢鏇襯壓鹹) = 遞獵積廠衊構壓遞鹽鏇 簾網構淵蓋壓積顧鏇淵 (簾窪構築廠餘齋襯範繭, 4.0 ~ 15.6) 更多 | ||||||
临床3期 | 3,323 | (範鑰壓憲願遞蓋簾簾艱): HR = 0.77 (95% CI, 0.56 ~ 1.08) | 积极 | 2002-08-01 | |||
Placebo |
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