SYNTHETIC COMMUNICATIONS
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2024
·
IF 1.8
Xin-Hao Hua,Fa-Qi Wang,Zhong-Jin Yang,Yuan Liu,Shu-Han Yang,Dong-Rong Zhu,Yu-Ming Liu
Herein, we designed a series of guanidinobenzoic acid ester derivatives on the basis of approved AP drugs, such as nafamostat, gabexate and camostat, and evaluated their inhibitory effects on trypsin and anti-inflammatory activity. Among them, five compounds (6a, 6c–6e, 7j) showed excellent inhibitory effects on trypsin with IC50 values of 0.0756 μM to 0.1227 μM, which are more potent than nafamostat and gabexate. Moreover, compounds 6a, 6b and 6c also showed significant inhibitory potency against the pro-inflammatory molecule NO with IC50 values of 1.618 μM, 2.276 μM, and 3.022 μM, respectively. Consequently, the potential lead compounds simultaneously with anti-trypsin and anti-inflammatory activities were identified, which would profit further structural optimization for the treatment of AP.
研究领域:
药物化学
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炎症研究
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消化系统疾病
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF GASTROENTEROLOGY
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2013
·Vol. 49
·期 3
·388-399
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IF 3.788
Yuhara Hiroki,Ogawa Masami,Kawaguchi Yoshiaki,Igarashi Muneki,Shimosegawa Tooru,Mine Tetsuya
Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is the most frequent complication of ERCP. Several meta-analyses have examined the effects of protease inhibitors (gabexate mesilate, ulinastatin, and nafamostat mesilate) and non-steroidal anti-inflammatory drugs (NSAIDs) on post-ERCP pancreatitis, but the results have been confusing. Since the previous meta-analysis, several new studies have been published on this topic. To provide an updated quantitative assessment of the effectiveness of protease inhibitors and NSAIDs in preventing post-ERCP pancreatitis, we conducted a meta-analysis of randomized trials for patients at risk of post-ERCP pancreatitis. Twenty-six articles were included in this meta-analysis. Nafamostat mesilate (summary RR = 0.41; 95 %CI 0.28–0.59; n = 4 studies) and NSAIDs (summary RR = 0.58; 95 %CI = 0.44–0.76; n = 7 studies) were associated with decreased risk of post-ERCP pancreatitis in the high-quality studies. However, gabexate mesilate (summary RR = 0.64; 95 %CI = 0.36–1.13; n = 6 studies) and ulinastatin (summary RR = 0.65; 95 %CI = 0.33–1.30; n = 2 studies) were not associated with decreased risk of post-ERCP pancreatitis in the high-quality studies. This is the first meta-analysis to compare the effects of three protease inhibitors. Solid evidence supports the use of nafamostat mesilate and NSAIDs for preventing post-ERCP pancreatitis.
研究领域:
消化病学
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介入内镜学
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胰腺疾病
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临床药理学
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循证医学
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围手术期管理
✓ 已验证
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Yanan Wang,Xinyuan Wang,Xue Zhang,Baomei Zhang,Xinlei Meng,Deyao Qian,Yatao Xu,Liangmin Yu,Xuefeng Yan,Zhiyu He
Severe acute pancreatitis (AP) is a life-threatening pancreatic inflammatory disease with a high mortality rate (∼40%). Existing pharmaceutical therapies in development or in clinical trials showed insufficient treatment efficacy due to their single molecular therapeutic target, poor water solubility, short half-life, limited pancreas-targeting specificity, etc. Herein, acid-responsive hollow mesoporous Prussian blue nanoparticles wrapped with neutrophil membranes and surface modified with the N,N-dimethyl-1,3-propanediamine moiety were developed for codelivering membrane-permeable calcium chelator BAPTA-AM (BA) and trypsin activity inhibitor gabexate mesylate (Ga). In the AP mouse model, the formulation exhibited efficient recruitment at the inflammatory endothelium, trans-endothelial migration, and precise acinar cell targeting, resulting in rapid pancreatic localization and higher accumulation. A single low dose of the formulation (BA: 200 μg kg–1, Ga: 0.75 mg kg–1) significantly reduced pancreas function indicators to close to normal levels at 24 h, effectively restored the cell redox status, reduced apoptotic cell proportion, and blocked the systemic inflammatory amplified cascade, resulting in a dramatic increase in the survival rate from 58.3 to even 100%. Mechanistically, the formulation inhibited endoplasmic reticulum stress (IRE1/XBP1 and ATF4/CHOP axis) and restored impaired autophagy (Beclin-1/p62/LC3 axis), thereby preserving dying acinar cells and restoring the cellular “health status”. This formulation provides an upstream therapeutic strategy with clinical translation prospects for AP management through synergistic ion homeostasis regulation and pancreatic autodigestion inhibition.
研究领域:
药学
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纳米技术
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炎症性疾病
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）