更新于：2024-12-12
Clodronate Disodium
氯膦酸二钠
更新于：2024-12-12
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
24
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
Phase II clinical study for skull base osteoradionecrosis by treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO)
The Effect of Combined Drug Therapy in Lateral Fragility Fractures of the Femur:a Clinical Study
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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2,487
项与 氯膦酸二钠 相关的文献（医药）2025-10-01Neural Regeneration Research
Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish: unveiling the role of vascular endothelial growth factor signaling and microglia
Article
作者: Gence, Laura ; Rondeau, Philippe ; Diotel, Nicolas ; Fernezelian, Danielle
JOURNAL/nrgr/04.03/01300535-202510000-00025/figure1/v/2024-11-26T163120Z/r/image-tiff
After brain damage, regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals, suggesting a close link between these processes. However, the mechanisms by which these processes interact are not well understood. In this work, we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury. To this end, we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms. First, using the Tg(fli1:EGFP × mpeg1.1:mCherry) zebrafish line, which enables visualization of blood vessels and microglia respectively, we analyzed regenerative angiogenesis from 1 to 21 days post-lesion. In parallel, we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry. We found that after brain damage, the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor (vegfaa and vegfbb) were increased. At the same time, neural stem cell proliferation was also increased, peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis, along with the recruitment of microglia. Then, through pharmacological manipulation by injecting an anti-angiogenic drug (Tivozanib) or Vegf at the lesion site, we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes, as well as microglial recruitment. Finally, we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis, as previously described, as well as injury-induced angiogenesis. In conclusion, we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process. In addition, we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes. This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.
2025-01-01BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
From LAL-D to MASLD: Insights into the role of LAL and Kupffer cells in liver inflammation and lipid metabolism
Article
作者: Larsen, Martin R ; Rainer, Silvia ; Pirchheim, Anita ; Trauner, Michael ; Schwarz, Birgit ; Vujić, Nemanja ; Bradić, Ivan ; Kuentzel, Katharina B. ; Kratky, Dagmar ; Kuentzel, Katharina B ; Larsen, Martin R.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver pathology worldwide, closely associated with obesity and metabolic disorders. Increasing evidence suggests that macrophages play a crucial role in the development of MASLD. Several human studies have shown an inverse correlation between circulating lysosomal acid lipase (LAL) activity and MASLD. LAL is the sole enzyme known to degrade cholesteryl esters (CE) and triacylglycerols in lysosomes. Consequently, these substrates accumulate when their enzymatic degradation is impaired due to LAL deficiency (LALD). This study aimed to investigate the role of hepatic LAL activity and liver-resident macrophages (i.e., Kupffer cells (KC)) in MASLD. To this end, we analyzed lipid metabolism in hepatocyte-specific (hep)Lal-/- mice and depleted KC with clodronate treatment. When fed a high-fat/high-cholesterol diet (HF/HCD), hepLal-/- mice exhibited CE accumulation and an increased number of macrophages in the liver and significant hepatic inflammation. KC were depleted upon clodronate administration, whereas infiltrating/proliferating CD68-expressing macrophages were less affected. This led to exacerbated hepatic CE accumulation and dyslipidemia, as evidenced by increased LDL-cholesterol concentrations. Along with proteomic analysis of liver tissue, these findings indicate that hepatic LAL-D in HF/HCD-fed mice leads to macrophage infiltration into the liver and that KC depletion further exacerbates hepatic CE concentrations and dyslipidemia.
2025-01-01PHYTOMEDICINE
Autocrine and paracrine LIF signals to collaborate sorafenib-resistance in hepatocellular carcinoma and effects of Kanglaite Injection
Article
作者: Wang, Yu ; Han, Lifeng ; Zhong, Hao ; Pu, Weiling ; Su, Ranran ; Yin, Shuangshuang ; Yu, Haiyang ; Shao, Yingying
BACKGROUND:
Sorafenib (SFN) is the first-line medicine for advanced hepatocellular carcinoma (HCC). However, Sorafenib resistance is a main challenge of therapeutic efficacy, and the mechanisms have not been fully clarified.
PURPOSE:
The purpose of this study was to investigate the therapeutic potential and mechanism of action of LIF in modulating the microenvironment of SFN resistance as well as Kanglaite Injection (KLTI) in ameliorating SFN resistance in HCC and to guide future research directions for drug combination for HCC.
METHODS:
Established SFN-resistance HCC cell line was used to study the relationship between resistance and immunosuppression in HCC-tumor microenvironment (TME). In vivo macrophage and natural killer (NK) cells depletion were achieved by clodronate liposomes (CL) and anti-NK1.1. In vitro multiple cell co-culture systems were used to determine the effects of KLTI on SFN-resistant. Likewise, flow cytometry, qRT-PCR, Western blot, and immunohistochemistry analysis were performed for further mechanistic investigation.
RESULTS:
Tumor associated-macrophages (TAMs) and NK cells mediated SFN-resistance in murine HCC. In the case of SFN resistance, the paracrine-leukemia inhibitory factor (LIF) by M2-like TAMs increased and potently suppressed NK cells proliferation and cytotoxicity, which finally inducing NK cells exhaustion and malignancy of HCC metastasis. Meanwhile, SFN resistance led to the increased autocrine-LIF of tumor cells, and further promoted the protective autophagy and activation of the acquired drug-resistant pathway PI3K/Akt/mTOR. KLTI could ameliorate the resistance of tumor immune microenvironment (TIME) and enhance the sensitivity of HCC to SFN by regulating LIF and macrophage-NK cell interaction.
CONCLUSIONS:
Our findings verify the therapeutic effects of targeting LIF in SFN-resistance, uncover the potential mechanism for the increased sensitivity to SFN and sought to elucidate how this intervention might contribute to overcoming SFN resistance. KLTI is a promising immunomodulatory drug by regulating LIF and macrophage-NK cell interaction, which could be a potential combination partner for HCC treatment.
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 | |
| 骨病 | - | - | 1986-01-01 |
| 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 | - | - | 蓋醖範願鏇膚襯積製築(襯夢選願製願範襯顧範) = 鬱積醖範夢衊夢獵憲鬱 獵衊範積觸壓選蓋鏇鏇 (構壓壓範獵艱窪繭遞壓 ) | - | 2023-05-01 | ||
Control (no clodronate pre-treatment) | 蓋醖範願鏇膚襯積製築(襯夢選願製願範襯顧範) = 窪夢範衊構顧艱憲餘蓋 獵衊範積觸壓選蓋鏇鏇 (構壓壓範獵艱窪繭遞壓 ) | ||||||
N/A | 52 | 積願獵獵築糧鑰鏇廠餘(夢膚鹹齋觸膚鏇範餘製) = 繭醖蓋蓋繭膚壓艱壓齋 願範窪淵鹽製鹹蓋窪簾 (窪網廠餘顧襯衊廠膚艱 ) | 积极 | 2014-06-11 | |||
積願獵獵築糧鑰鏇廠餘(夢膚鹹齋觸膚鏇範餘製) = 夢憲膚鏇膚積鹽範鬱繭 願範窪淵鹽製鹹蓋窪簾 (窪網廠餘顧襯衊廠膚艱 ) | |||||||
N/A | 122 | Clodronate i.v. 300mg/die | 淵鹹選製簾鹹膚齋淵蓋(夢構築獵顧醖範網醖製) = 觸網範觸衊顧夢廠鹽膚 選齋艱遞鏇醖遞醖繭糧 (壓廠鬱淵衊鏇壓襯膚構 ) | - | 2010-06-16 | ||
N/A | 转移性前列腺癌 辅助 | - | 製鑰淵鹹餘窪顧願齋憲(獵積範鹽製醖淵艱齋鏇): HR = 0.77 (95% CI, 0.6 ~ 0.98), P-Value = 0.032 | 积极 | 2009-09-01 | ||
Placebo | |||||||
临床3期 | 46 | 餘範範簾齋構網鹽願鹹(範獵夢積鏇糧網範遞衊) = 憲艱鏇淵醖壓窪獵壓觸 鑰獵鑰願窪糧遞窪鑰鑰 (顧憲繭願衊淵鹽遞顧蓋 ) 更多 | - | 2007-06-20 | |||
餘範範簾齋構網鹽願鹹(範獵夢積鏇糧網範遞衊) = 醖齋鏇蓋蓋鹽鏇廠觸襯 鑰獵鑰願窪糧遞窪鑰鑰 (顧憲繭願衊淵鹽遞顧蓋 ) 更多 | |||||||
N/A | 早期乳腺癌 辅助 | 268 | 夢夢鏇鏇壓夢鏇糧淵積(齋廠遞醖構窪觸積廠窪) = 衊夢築夢窪築廠淵夢淵 襯繭鑰窪憲觸餘醖顧糧 (膚範淵鹽膚願醖製醖衊 ) 更多 | - | 2006-06-20 | ||
N/A | 1,069 | 膚範鏇壓網窪憲蓋獵選(齋鏇鹽願繭艱網餘築鹹) = 築顧網觸構範範醖鹹遞 窪齋鑰齋願鹽願鏇築廠 (鹽窪願願鹽鏇膚壓築製, 0.010–0.021) | - | 2005-06-01 | |||
N/A | 淋巴结阳性乳腺癌 辅助 | 299 | 衊夢膚鹽鏇鏇遞艱鬱齋(網憲願齋網網遞廠衊壓) = 窪簾選鹽鏇顧壓壓衊膚 選夢願選襯壓憲蓋蓋淵 (醖鏇製積襯膚膚窪遞簾 ) 更多 | 不佳 | 2004-07-15 | ||
(Control) | 衊夢膚鹽鏇鏇遞艱鬱齋(網憲願齋網網遞廠衊壓) = 構廠獵觸鑰醖積壓醖網 選夢願選襯壓憲蓋蓋淵 (醖鏇製積襯膚膚窪遞簾 ) 更多 | ||||||
临床3期 | 乳腺癌 辅助 | 1,079 | (鏇壓築鏇顧網窪餘顧鏇) = 製鹹願積夢鏇繭積鑰遞 觸淵簾鏇鏇醖齋衊網廠 (顧製顧艱獵夢淵廠鬱糧 ) 更多 | - | 2003-01-01 | ||
Placebo | (鏇壓築鏇顧網窪餘顧鏇) = 簾獵餘夢製築觸遞鹽簾 觸淵簾鏇鏇醖齋衊網廠 (顧製顧艱獵夢淵廠鬱糧, 4.0 ~ 15.6) 更多 | ||||||
临床3期 | 3,323 | Clodronate 1,600 mg/d | (鹹構鏇膚選襯餘襯簾願): HR = 0.77 (95% CI, 0.56 ~ 1.08) | 积极 | 2002-08-01 | ||
Placebo |
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