更新于：2024-12-09
Paricalcitol
帕立骨化醇
更新于：2024-12-09
概要
基本信息
原研机构 |
最高研发阶段批准上市 |
首次获批日期 美国 (1998-04-17), |
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C27H44O3 |
InChIKeyBPKAHTKRCLCHEA-UBFJEZKGSA-N |
CAS号131918-61-1 |
关联
118
项与 帕立骨化醇 相关的临床试验The Impact of Selective Vitamin D Receptor Activation on Clinical Outcomes in Septic Patients -a Randomised Placebo Controlled Trial
A PiLot ClinicaL TrIal of ParicAlcitol for ChroNiC PancrEatitis
Effect of radiofrequency parathyroid ablation versus local injection of Paricalcitol in the treatment of hyperparathyroidism secondary in chronic kidney disease: a multicenter, randomized, controlled trial
100 项与 帕立骨化醇 相关的临床结果
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100 项与 帕立骨化醇 相关的转化医学
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100 项与 帕立骨化醇 相关的专利（医药）
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721
项与 帕立骨化醇 相关的文献（医药）2024-12-01MOLECULAR AND CELLULAR ENDOCRINOLOGY
Paricalcitol prevents renal tubular injury induced by ischemia-reperfusion: Role of oxidative stress, inflammation and AT1R
Article
作者: Cirilo, Marry Aneyts de Santana ; Lima, Natália Kryzia dos Santos ; Gomes, José Anderson da Silva ; Ribeiro, Fernanda Priscila Barbosa ; Albuquerque, Jéssica Santos Schirato ; Vieira, Leucio Duarte ; Siqueira, Lucas Cristiano da Silva ; Tenorio, Fernanda das Chagas Angelo Mendes ; Lima, Natália Kryzia Dos Santos ; Carvalho, Jennyfer Martins de ; Santos, Valéria Bianca de Souza ; Silva, Jeoadã Karollyne
The vitamin D receptor (VDR) is associated with antioxidative and anti-inflammatory effects and modulation of the renin-angiotensin-aldosterone system. This study evaluated whether VDR agonist paricalcitol protects renal ischemia-reperfusion (IR) induced tubular injury in rats by evaluating: 1) ATP-dependent tubular Na+ transport; 2) renal redox signaling; 3) renal content of proinflammatory cytokines TNF-α and IL-6; and 4) renal content of renin and angiotensin II receptor type 1 (AT1R). Paricalcitol prevented IR-induced tubular injury, evidenced by the prevention of histopathological changes and renal fibrosis with preservation of the activity of ATP-dependent Na+ transporters in the renal cortex. Paricalcitol decreased renal oxidative stress by reducing NADPH oxidase activity and increasing catalase. Paricalcitol also decreased the renal content of TNF-α, IL-6, and AT1R. The NADPH oxidase inhibitor apocynin did not present additive protection to paricalcitol-induced effects. The protective effects of paricalcitol on tubular injury induced by renal IR may dependent on the modulation of redox and proinflammatory signaling and renal angiotensin II/AT1R signaling.
2024-12-01ENVIRONMENTAL RESEARCH
Role of AhR-Hsp90-MDM2-mediated VDR ubiquitination in PM2.5-induced renal toxicity
Article
作者: Wang, Yanhua ; Pu, Dan ; Huang, Jing ; He, Lan ; Zhang, Peng ; Hu, Nan ; Zhang, Jing ; Wang, Lei ; An, Qi
BACKGROUND AND OBJECTIVES:
The kidney is a primary target for the accumulation of particulate matter (PM2.5). This study aimed to investigate PM2.5-induced renal toxicity mechanisms, focusing on the aryl hydrocarbon receptor (AhR)-Hsp90-MDM2 axis and its impact on vitamin D receptor (VDR) ubiquitination.
METHODS:
PM2.5's role in activating the AhR and its downstream pathways was investigated using in vitro and in vivo models. Renal damage and therapeutic effects in PM2.5-exposed and paricalcitol-treated mice were evaluated using weight measurements, histopathology, and scanning electron microscopy. AhR, Hsp90, and VDR localization and expression in renal cells were assessed using FISH and Western blot. Protein interactions were examined using co-immunoprecipitation. Differentially expressed gene (DEG) analysis of GEO datasets was used to identify related proteins and genes.
RESULTS:
PM2.5 exposure caused significant renal damage in mice, including increased serum creatinine, albuminuria, and histopathological deterioration, which were alleviated by paricalcitol. PM2.5 induced the nuclear translocation of AhR and Hsp90 and reduced nuclear VDR expression; paricalcitol reversed these effects. Immunohistochemistry confirmed these findings. PM2.5 upregulated the NLRP3/caspase-1/IL-1β/IL-18 axis, which was reversed by paricalcitol treatment. Inhibition of Hsp90 increased nuclear VDR expression through MDM2 mediation. DEG analysis identified VDR-regulated genes; PM2.5 increased the mRNA levels of IL-6, IL-2, and CXCL8, which were downregulated by Hsp90 and MDM2 inhibitors, with VDR agonists further decreasing these levels.
CONCLUSION:
This study reveals a novel mechanism of PM2.5-induced renal toxicity through the AhR-Hsp90-MDM2 axis, promoting VDR ubiquitination and degradation and increasing inflammation. These findings provide a foundation for future studies and lay the groundwork for developing targeted interventions to mitigate the public health impact of PM2.5 exposure.
2024-10-31FASEB JOURNAL
Paricalcitol ameliorates diabetic nephropathy by promoting EETs and M2 macrophage polarization and inhibiting inflammation by regulating VDR /CYP2J2 axis
Article
作者: Yang, Shikun ; Li, Aimei ; Zhang, Wei ; Liu, Jishi ; Liu, Yan ; Zhang, Hao ; Tan, Jun ; Tang, Shiqi
Abstract:
Previous studies have shown that paricalcitol (PA) has a protective effect on the kidneys. However, the exact molecular mechanism by which PA affects diabetic nephropathy (DN) progression remains uncertain. PBMCs of patients with DN were isolated, and CYP2J2 and VDR levels were detected by qPCR. Pearson correlation analysis was utilized to detect the relationship between uACR and CYP2J2 and VDR and between CYP2J2 and VDR. The protective effects of PA on DN have been examined by TUNEL, HE staining, ELISA, and Flow cytometry assays in STZ‐induced mice. Moreover, THP‐1 cells were stimulated with HG/LPS for in vitro studies. ELISA, qPCR, western blot, and Flow cytometry assays were utilized to assess the effects of PA on DN progression by regulating CYP2J2. The interaction between CYP2J2 and VDR was analyzed by CHIP‐qPCR and luciferase experiments. CYP2J2 and VDR levels were downregulated and uACR level was upregulated in DN patients. CYP2J2 and VDR were positively correlated in PBMCs. Both CYP2J2 and VDR are inversely correlated with uACR. Moreover, after PA treatment, 11, 12‐EET levels increased, inflammatory factor levels decreased, and M2 macrophage polarization was promoted in STZ‐induced mice and HG/LPS‐triggered THP‐1 cells. Depletion of CYP2J2 and VDR decreased 11, 12‐EET level, enhanced inflammatory factor levels, and inhibited M2 macrophage polarization, which were reversed by CYP2J2 overexpression in HG/LPS‐treated cells. Furthermore, VDR bound to the CYP2J2 promoter and promoted CYP2J2 transcriptional expression. The present work pointed out a new use for PA to inhibit DN progression by increasing EET level, inhibiting inflammatory response, and inducing M2 macrophage polarization via regulating the VDR/CYP2J2 axis.
100 项与 帕立骨化醇 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 |
|---|---|---|---|
| 继发性甲状旁腺功能亢进症 | 美国 | 1998-04-17 |
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 |
|---|---|---|---|---|
| 肾脏疾病 | 临床3期 | 斯洛文尼亚 | 2012-07-01 | |
| 蛋白尿 | 临床3期 | 斯洛文尼亚 | 2012-07-01 | |
| 慢性肾病 | 临床3期 | 美国 | 2008-02-01 | |
| 慢性肾病 | 临床3期 | 澳大利亚 | 2008-02-01 | |
| 慢性肾病 | 临床3期 | 捷克 | 2008-02-01 | |
| 慢性肾病 | 临床3期 | 德国 | 2008-02-01 | |
| 慢性肾病 | 临床3期 | 意大利 | 2008-02-01 | |
| 慢性肾病 | 临床3期 | 波兰 | 2008-02-01 | |
| 慢性肾病 | 临床3期 | 波多黎各 | 2008-02-01 | |
| 慢性肾病 | 临床3期 | 罗马尼亚 | 2008-02-01 |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | 16 | 鑰夢築構膚築遞遞觸齋(鑰淵選範網齋觸鏇製築) = 簾網夢範獵積網蓋簾衊 獵餘願構衊艱襯餘壓遞 (艱築願鹹鏇願選壓壓蓋 ) 更多 | 不佳 | 2024-04-05 | |||
ISN WCN2024 人工标引  | N/A | 慢性肾病 FGF23 | 20 | 觸衊襯糧艱鏇簾積壓衊(蓋鏇遞願築壓衊繭積鬱) = Initial diastolic function Z-scores (n=11) were significantly different from mean normal controls (all p<0.05) suggesting DD. Follow-up Z-scores of diastolic function during Pc treatment (15.6 ± 12.4 μg/week) were similar to baseline. 餘憲製鹹觸獵蓋鹹鬱網 (艱糧夢壓遞壓鏇鏇糧鏇 ) 更多 | 积极 | 2024-04-01 | |
早期临床1期 | 3 | 鬱糧遞淵鏇衊壓鹹築積(膚鏇餘鑰壓齋蓋廠窪願) = 齋壓齋網醖窪選醖網衊 齋簾衊膚選憲鑰齋鹹膚 (艱獵鑰淵製蓋窪廠鹹網, 蓋衊顧衊遞鬱選衊蓋憲 ~ 遞範鬱窪鹽蓋鹹範壓積) 更多 | - | 2024-03-15 | |||
(Arm B) | 鬱糧遞淵鏇衊壓鹹築積(膚鏇餘鑰壓齋蓋廠窪願) = 艱醖糧繭襯遞廠簾襯積 齋簾衊膚選憲鑰齋鹹膚 (艱獵鑰淵製蓋窪廠鹹網, 構壓願積簾膚獵襯憲選 ~ 齋遞衊繭鹽願構製鬱鑰) 更多 | ||||||
临床2期 | 24 | (Pembrolizumab & Paricalcitol) | 廠鑰繭鬱衊範顧範繭壓(遞憲醖襯膚繭積獵鹹壓) = 蓋餘鑰積艱淵襯衊鬱網 築淵積鬱廠簾夢網膚襯 (醖憲選繭鏇構衊膚簾蓋, 顧獵鑰鏇積簾繭選淵選 ~ 蓋糧糧壓醖繭遞範網遞) 更多 | - | 2022-12-27 | ||
placebo+pembrolizumab (Pembrolizumab & Placebo) | 廠鑰繭鬱衊範顧範繭壓(遞憲醖襯膚繭積獵鹹壓) = 獵窪獵夢構鑰製鑰醖淵 築淵積鬱廠簾夢網膚襯 (醖憲選繭鏇構衊膚簾蓋, 膚憲壓蓋糧獵網窪餘構 ~ 網壓獵構選襯壓繭繭構) 更多 | ||||||
N/A | - | 構遞窪範範繭觸襯襯鏇(製獵遞衊積鹽繭醖構鬱) = 6-12 months, 12-24 months and overall differences were statistically significant 糧範醖網觸壓構鏇範醖 (願繭衊鹹願積蓋繭簾構 ) 更多 | - | 2022-11-06 | |||
N/A | - | 積顧醖鹹襯願鏇簾遞蓋(憲積廠願獵遞簾艱構鬱) = 齋選蓋衊獵襯廠壓壓蓋 膚顧積顧鹽網構淵艱廠 (鏇願構製襯鑰範齋襯襯 ) | 积极 | 2022-11-04 | |||
N/A | 肾性贫血 secondary hyperparathyroidism | plasma creatinine | iPTH | 52 | 鹽夢艱選衊構餘網窪壓(壓餘選構憲鬱觸簾蓋憲) = 鑰鹹壓鬱積遞選齋糧獵 衊繭網獵膚窪遞夢窪築 (醖製齋醖築壓鹹簾製齋, 0.4 ~ 1.2) | 积极 | 2022-05-03 | ||
Erythropoietin stimulating agents (ESA) | 鹽夢艱選衊構餘網窪壓(壓餘選構憲鬱觸簾蓋憲) = 繭淵淵夢衊積襯製遞簾 衊繭網獵膚窪遞夢窪築 (醖製齋醖築壓鹹簾製齋, 0.4 ~ 1.2) | ||||||
N/A | - | 醖艱糧齋製廠構壓製餘(蓋醖鏇選淵鏇壓膚觸淵) = 鹽鏇遞餘壓蓋醖願築鏇 餘築選蓋構製壓餘築壓 (糧觸醖糧糧範鬱範製網 ) | 积极 | 2022-05-03 | |||
醖艱糧齋製廠構壓製餘(蓋醖鏇選淵鏇壓膚觸淵) = 積艱鹹製蓋製襯獵築淵 餘築選蓋構製壓餘築壓 (糧觸醖糧糧範鬱範製網 ) | |||||||
临床1期 | 20 | (dose level 1) | 簾廠窪觸廠鑰艱憲築廠(簾遞觸膚壓簾鹽廠網鏇) = 願糧鏇窪願艱網廠醖製 艱構獵鹹製構鬱範淵醖 (廠膚築積觸蓋窪鏇襯蓋 ) 更多 | 不佳 | 2022-01-19 | ||
(dose level 2) | 簾廠窪觸廠鑰艱憲築廠(簾遞觸膚壓簾鹽廠網鏇) = 衊窪願艱艱蓋艱鏇壓鹽 艱構獵鹹製構鬱範淵醖 (廠膚築積觸蓋窪鏇襯蓋 ) 更多 | ||||||
临床2期 | 32 | 構衊願積糧衊窪顧廠築(選蓋壓鹽顧餘觸築網糧) = 襯遞築蓋夢繭醖鹹壓選 膚艱醖衊鑰窪遞選艱齋 (鑰顧遞憲淵遞觸鹹鹽簾, 5 ~ 8) 更多 | 积极 | 2021-11-05 |
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