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更新于：2025-01-25
Alanylglutamine
丙氨酰谷氨酰胺
更新于：2025-01-25
概要
基本信息
最高研发阶段批准上市 |
首次获批日期 德国 (1995-04-01) |
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/序列
分子式C8H15N3O4 |
InChIKeyHJCMDXDYPOUFDY-WHFBIAKZSA-N |
CAS号39537-23-0 |
关联
19
项与 丙氨酰谷氨酰胺 相关的临床试验PACTR202303692483097
Efficacy of Perioperative Infusion of N (2)-L-alanyl-L-glutamine in Glycemic Control for Patients With Uncontrolled Diabetes Mellitus Presented for Urgent Coronary Artery Bypass Surgery: Randomized Control Trial
ISRCTN13489936
The ameliorative potential of L-alanyl L-glutamine dipeptide in colon cancer patients receiving modified FOLFOX-6 regarding the incidence of diarrhea, the treatment response, and patients’ survival: a randomized controlled trial
NCT04305769
Alanyl-glutamine Supplementation of Standard Treatment for C. Difficile Infection: a Randomized, Double-blind, Placebo-controlled Trial
100 项与 丙氨酰谷氨酰胺 相关的临床结果
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100 项与 丙氨酰谷氨酰胺 相关的转化医学
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100 项与 丙氨酰谷氨酰胺 相关的专利（医药）
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855
项与 丙氨酰谷氨酰胺 相关的文献（医药）2025-01-01GASTROENTEROLOGY
Glutamine Supplementation as a Novel Metabolic Therapeutic Strategy for LIG3-Dependent Chronic Intestinal Pseudo-Obstruction
Article
作者: Costanzini, Anna ; Bonora, Elena ; Pironi, Loris ; Boschetti, Elisa ; Diquigiovanni, Chiara ; Carelli, Valerio ; Fato, Romana ; Valenti, Francesca ; Rizzardi, Nicola ; De Giorgio, Roberto ; Arrigo, Serena ; Maresca, Alessandra ; Giangregorio, Tania ; Taniguchi-Ikeda, Mariko ; Orsini, Arianna ; Isidori, Federica ; Magnoni, Penelope ; Gozzellino, Livia ; Astolfi, Annalisa ; Cataldi-Stagetti, Erica ; Bergamini, Christian
BACKGROUND & AIMS:
We recently identified a recessive syndrome due to DNA ligase 3 (LIG3) mutations in patients with chronic intestinal pseudo-obstruction, leukoencephalopathy, and neurogenic bladder. LIG3 mutations affect mitochondrial DNA maintenance, leading to defective energy production. We aimed at identifying altered molecular pathways and developing possible targeted treatments to revert/ameliorate the cellular energy impairment.
METHODS:
Whole transcriptome analysis was performed on patient-derived fibroblasts total RNA and controls. Mitochondrial function, mitophagy, and l-glutamine supplementation effects were analyzed by live cell analysis, immunostaining, and Western blot. Patients were treated with Dipeptiven (Fresenius-Kabi) according to standard protocols. Patients' symptoms were analyzed by the Gastrointestinal Symptom Rating Scale questionnaire.
RESULTS:
We identified deregulated transcripts in mutant fibroblasts vs controls, including overexpression of genes involved in extracellular matrix development and remodeling and mitochondrial functions. Gut biopsy specimens of LIG3-mutant patients documented collagen and elastic fiber accumulation. Mutant fibroblasts exhibited impaired mitochondrial mitophagy indicative of dysfunctional turnover and altered Ca2+ homeostasis. Supplementation with l-glutamine (6 mmol/L), previously shown to increase mitochondrial DNA-defective cell survival, improved growth rate and adenosine 5'-triphosphate production in LIG3-mutant fibroblasts. These data led us to provide parenterally a dipeptide containing l-glutamine to 3 siblings carrying biallelic LIG3 mutations. Compared with baseline, gastrointestinal and extra-gastrointestinal symptoms significantly improved after 8 months of treatment.
CONCLUSIONS:
LIG3 deficiency leads to mitochondrial dysfunction. High levels l-glutamine supplementation were beneficial in LIG3-mutant cells and improved symptom severity without noticeable adverse effects. Our results provide a proof of concept to design ad hoc clinical trials with l-glutamine in LIG3-mutant patients.
2025-01-01JOURNAL OF CHROMATOGRAPHY A
Nontarget analysis of natural flavor metabolites in tobacco extracts
Article
作者: Yang, Chun-Qiang ; Wang, Jian-Wei ; Ren, Meng ; Xu, Xiu-Juan ; Wang, Ren-Qi ; Wang, Min ; Liu, Shan
Large-scale production of tobacco generates significant amounts of waste, making the reuse and recycling of tobacco waste crucial for sustainability. However, the high diversity of tobacco metabolites requires a comprehensive analysis of tobacco waste extracts, so as to optimize extraction selectivity and recovery. In this study, we thoroughly analyzed the metabolic composition of 168 tobacco extracts using nontarget analysis. The extracts were derived from 56 tobacco wastes covering all four major tobacco types: flue-cured, dark air-cured, Burley, and Oriental tobaccos. From each sample, we obtained three types of extracts, such as concretes, absolutes, and supercritical fluid extraction (SFE) oils, through various extraction protocols. By matching deconvolved experimental MS/MS spectra with databases, 587 metabolites were putatively annotated, which were categorized into 24 groups, including alkaloids, indoles, and flavor compounds. The metabolic compositions of extracts from dark air-cured and Burley tobaccos were found to be similar, whereas flue-cured and Oriental tobaccos contained more diverse flavor components. Notably, concretes of various tobaccos prepared with 70 %-ethanol contained similar amounts of addictive alkaloids. However, the absolutes obtained by sequential extraction of these concretes with 95 %-ethanol effectively removed alkaloids while modestly maintaining the flavor compounds. Conversely, extraction protocols incorporating supercritical fluid extraction followed by 95 %-ethanol extraction resulted in the loss of most flavor compounds, likely due to the incompatibility between the solvents used in the two extraction steps. In conclusion, our study demonstrates that absolutes derived through secondary extraction with varying ethanol-water ratios holds significant potential for utilization.
2025-01-01JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Liver lipid metabolism, oxidative stress, and inflammation in glutamine-supplemented ob/ob mice
Article
作者: Munhoz, Ana Cláudia ; Jr, Jose Donato ; Vilas-Boas, Eloisa Aparecida ; Takahashi, Hilton K ; Araújo, Layanne C C ; Leite, Jaqueline Santos Moreira ; Carpinelli, Angelo Rafael ; Carvalho, Carla Roberta ; Cruzat, Vinicius ; Curi, Rui
Glutamine availability may be reduced in chronic diseases, such as type 2 diabetes mellitus (T2DM)-induced by obesity. Herein, the antioxidant, anti-inflammatory and lipid metabolism effects of chronic oral glutamine supplementation in its free and dipeptide form were assessed in ob/ob mice. Adult male C57BL/6J ob/ob mice were supplemented with L-alanyl-L-glutamine (DIP) or free L-glutamine (GLN) in the drinking water for 40 days, whilst C57BL/6J Wild-type lean (WT) and control ob/ob mice (CTRL) received fresh water only. Plasma and tissue (skeletal muscle and liver) glutamine levels, and insulin resistance parameters (e.g., GTT, ITT, insulin) were determined. Oxidative stress (e.g., GSH system, Nrf2 translocation), inflammatory (e.g., NFkB translocation, TNF-α gene expression) and lipid metabolism parameters (e.g., plasma and liver triglyceride levels, SRBP-1, FAS, ACC, and ChRBP gene expression) were also analyzed. CTRL ob/ob mice showed lower glutamine levels in plasma and tissue, as well as increased insulin resistance and fat in the liver. Conversely, chronic DIP supplementation restored glutamine levels in plasma and tissues, improved glucose homeostasis and reduced plasma and liver lipid levels. Also, Nrf2 restoration, reduced NFkB translocation, and lower TNF-α gene expression was observed in the DIP group. Interestingly, chronic free GLN only increased muscle glutamine stores but reduced overall insulin resistance, and attenuated plasma and liver lipid metabolic biomarkers. The results presented herein indicate that restoration of body glutamine levels reduces oxidative stress and inflammation in obese and T2DM ob/ob mice. This effect attenuated hepatic lipid metabolic changes observed in obesity.
100 项与 丙氨酰谷氨酰胺 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 |
|---|---|---|---|
| 谷氨酰胺缺乏症 | 中国 | 1999-04-03 |
未上市
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 终末期肾脏病 | 临床2期 | 奥地利 | 2022-03-16 | |
| 腹膜炎 | 临床2期 | 奥地利 | 2014-06-02 | |
| 膳食补充剂 | 临床1期 | 中国 | - | |
| 膳食补充剂 | 临床1期 | 中国 | - | |
| 腹膜纤维变性 | 临床前 | 荷兰 | 2015-11-03 |
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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
临床3期 | 60 | (Glutamine) | 網鹽襯糧願壓簾遞醖願(淵夢選鏇鬱蓋鏇齋繭膚) = 範廠膚淵餘襯鑰鹹構積 製選鬱糧築範願膚鑰壓 (憲膚窪鹽顧憲餘淵願顧, 淵壓淵構憲糧鏇壓糧遞 ~ 淵構齋願窪選範顧鑰鬱) 更多 | - | 2023-11-13 | ||
Placebo (Control) | 網鹽襯糧願壓簾遞醖願(淵夢選鏇鬱蓋鏇齋繭膚) = 繭憲窪廠繭窪餘顧網願 製選鬱糧築範願膚鑰壓 (憲膚窪鹽顧憲餘淵願顧, 齋構壓淵艱獵鏇簾夢齋 ~ 範願襯選鹽膚鹹膚糧醖) 更多 | ||||||
临床2期 | 7 | 簾遞膚築鹽鑰顧壓艱鹽(齋範遞鬱蓋鹽遞簾網醖) = 觸餘夢簾鏇鑰蓋鏇襯構 觸鏇鏇鹹壓遞範觸鏇顧 (繭鬱廠憲鏇膚積衊網願, 壓窪鬱顧醖鬱範觸願鹹 ~ 鹹鑰遞築衊觸艱膚糧繭) 更多 | - | 2022-06-07 | |||
N/A | - | - | (Peritoneal Dialysis Fluid (PDF)) | 鑰鏇衊醖鹽獵積廠襯廠(鹹遞鑰廠鏇積網製廠衊) = 繭範製積壓積餘製顧蓋 製願衊鹹糧鏇構選積齋 (範願餘遞簾夢積衊選繭 ) | - | 2017-05-26 | |
Peritoneal Dialysis Fluid (PDF) + Alanyl-Glutamine (AlaGln) | 鑰鏇衊醖鹽獵積廠襯廠(鹹遞鑰廠鏇積網製廠衊) = 艱糧夢膚觸憲夢淵築鹽 製願衊鹹糧鏇構選積齋 (範願餘遞簾夢積衊選繭 ) | ||||||
N/A | 腹膜透析相关性腹膜炎 peritoneal leukocyte immuno-competence | peritoneal leukocyte transcriptome status | 6 | (Standard PD fluid (Physioneal40 3.86%, Baxter)) | 繭觸簾憲醖齋窪鹽製餘(窪獵鹽廠膚遞鹹願鬱齋) = 糧遞鬱壓鬱積鏇夢夢鑰 衊齋醖淵鑰積夢餘製範 (構繭簾蓋築餘醖夢積窪 ) | 积极 | 2015-11-03 | |
AlaGln-supplemented PD fluid | 繭觸簾憲醖齋窪鹽製餘(窪獵鹽廠膚遞鹹願鬱齋) = 鹹鬱艱簾壓衊築艱鏇積 衊齋醖淵鑰積夢餘製範 (構繭簾蓋築餘醖夢積窪 ) | ||||||
临床3期 | 150 | (Glutamine Dipeptide) | 餘鏇構艱齋襯遞醖鏇齋(憲醖範願蓋鹽襯醖製壓) = 鏇積壓夢獵積製遞選繭 廠製衊淵積簾膚築襯憲 (醖鹽齋膚築範憲齋壓鹽, 選簾鹹糧廠糧蓋齋廠構 ~ 簾網窪鏇壓壓窪獵襯壓) 更多 | - | 2014-02-13 | ||
15% Clinisol (Standard) | 餘鏇構艱齋襯遞醖鏇齋(憲醖範願蓋鹽襯醖製壓) = 醖網願夢鏇遞製繭網淵 廠製衊淵積簾膚築襯憲 (醖鹽齋膚築範憲齋壓鹽, 獵醖餘餘觸簾選醖網遞 ~ 淵蓋簾願壓範蓋獵壓顧) 更多 |
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