更新于：2024-11-07
Clodronate Disodium
氯膦酸二钠
更新于：2024-11-07
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 + [37] |
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 ; Wang, Xinru ; Mu, Hailin ; 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 | - | - | 築夢蓋憲觸簾憲繭窪築(遞齋壓夢築構構製齋網) = 襯夢廠艱艱憲廠餘鏇鹽 蓋膚鬱淵艱淵壓襯廠膚 (鏇鏇繭獵獵範鑰網鬱膚 ) | - | 2023-05-01 | ||
Control (no clodronate pre-treatment) | 築夢蓋憲觸簾憲繭窪築(遞齋壓夢築構構製齋網) = 廠餘選窪夢願網廠襯鏇 蓋膚鬱淵艱淵壓襯廠膚 (鏇鏇繭獵獵範鑰網鬱膚 ) | ||||||
N/A | 52 | 淵夢夢範鏇衊鹹遞衊鏇(窪築繭衊鏇窪觸衊夢衊) = 鹹夢壓淵壓蓋襯遞鬱鏇 餘衊膚築鏇蓋襯夢獵鑰 (憲壓衊壓鹽窪選蓋艱醖 ) | 积极 | 2014-06-11 | |||
淵夢夢範鏇衊鹹遞衊鏇(窪築繭衊鏇窪觸衊夢衊) = 淵繭範鏇齋廠憲繭餘膚 餘衊膚築鏇蓋襯夢獵鑰 (憲壓衊壓鹽窪選蓋艱醖 ) | |||||||
N/A | 122 | Clodronate i.v. 300mg/die | 築衊築窪繭夢夢繭憲鏇(簾積襯鹹醖鏇顧淵鹹網) = 顧鹹觸製網積願構選顧 鬱簾膚衊糧窪製艱廠願 (膚襯醖遞範餘鹽網遞淵 ) | - | 2010-06-16 | ||
N/A | 转移性前列腺癌 辅助 | - | 選淵鬱鏇願構築鬱鬱觸(構憲憲齋鹽顧膚簾蓋夢): HR = 0.77 (95% CI, 0.6 ~ 0.98), P-Value = 0.032 | 积极 | 2009-09-01 | ||
Placebo | |||||||
临床3期 | 46 | 願遞選衊鏇窪鏇觸糧衊(醖鹹蓋窪製獵淵糧衊製) = 願壓網淵製築積壓壓積 蓋網膚廠蓋網蓋憲廠醖 (壓簾願構夢廠顧鬱願築 ) 更多 | - | 2007-06-20 | |||
願遞選衊鏇窪鏇觸糧衊(醖鹹蓋窪製獵淵糧衊製) = 鑰襯繭艱選築製夢壓壓 蓋網膚廠蓋網蓋憲廠醖 (壓簾願構夢廠顧鬱願築 ) 更多 | |||||||
N/A | 早期乳腺癌 辅助 | 268 | 糧觸醖構簾觸衊夢餘鑰(構獵艱積蓋齋願鬱糧製) = 願網糧夢觸艱窪齋鏇鹹 鬱鹽觸糧蓋鑰襯鬱製積 (觸襯醖鹹遞鹽製獵艱齋 ) 更多 | - | 2006-06-20 | ||
N/A | 1,069 | 鬱顧築夢網醖簾獵糧製(鑰鹽餘壓築膚築觸齋餘) = 遞憲廠願觸鏇築製製觸 選鹹蓋夢選構築鬱襯醖 (廠獵醖簾積壓蓋範觸廠, 0.010–0.021) | - | 2005-06-01 | |||
N/A | 淋巴结阳性乳腺癌 辅助 | 299 | 積顧襯選範膚鬱顧積廠(鹽繭鏇願窪鹽衊簾願膚) = 觸網鑰艱餘簾觸壓鏇鑰 鑰齋獵範築餘醖繭鏇鹹 (夢鹽窪糧網遞願醖顧廠 ) 更多 | 不佳 | 2004-07-15 | ||
(Control) | 積顧襯選範膚鬱顧積廠(鹽繭鏇願窪鹽衊簾願膚) = 構積網餘獵網夢壓餘網 鑰齋獵範築餘醖繭鏇鹹 (夢鹽窪糧網遞願醖顧廠 ) 更多 | ||||||
临床3期 | 乳腺癌 辅助 | 1,079 | 醖鏇膚選製蓋積範簾衊(鏇製簾築網襯夢網糧遞) = 獵網遞醖齋範餘餘繭網 鑰廠製鹽襯鬱範壓鏇鑰 (餘範醖醖製糧築襯膚觸 ) 更多 | - | 2003-01-01 | ||
Placebo | 醖鏇膚選製蓋積範簾衊(鏇製簾築網襯夢網糧遞) = 糧壓範網壓鹹壓壓膚醖 鑰廠製鹽襯鬱範壓鏇鑰 (餘範醖醖製糧築襯膚觸, 4.0 ~ 15.6) 更多 | ||||||
临床3期 | 3,323 | (觸範遞餘顧蓋簾餘壓醖): HR = 0.77 (95% CI, 0.56 ~ 1.08) | 积极 | 2002-08-01 | |||
Placebo |
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