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更新于：2025-01-13
Alanylglutamine
丙氨酰谷氨酰胺
更新于：2025-01-13
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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493
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: Bonora, Elena ; Costanzini, Anna ; Boschetti, Elisa ; Pironi, Loris ; Diquigiovanni, Chiara ; Carelli, Valerio ; Fato, Romana ; Valenti, Francesca ; Rizzardi, Nicola ; De Giorgio, Roberto ; Arrigo, Serena ; Giangregorio, Tania ; Maresca, Alessandra ; Taniguchi-Ikeda, Mariko ; Orsini, Arianna ; Isidori, Federica ; Magnoni, Penelope ; Gozzellino, Livia ; Astolfi, Annalisa ; Bergamini, Christian ; Cataldi-Stagetti, Erica
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.
2024-12-01POULTRY SCIENCE
Transcriptomic analysis of ileal adaptations and growth responses in growing hens supplemented with alanyl-glutamine dipeptide
Article
作者: Yang, Haiming ; Yang, Zhi ; Zheng, Xucheng ; Fu, Zhenming ; Zafar, Muhamamd Hammad ; Nazir, Usman ; Wang, Zhiyue
The growing phase of laying hens is crucial for growth and development due to its direct impact on their productivity during laying phase. During initial growth phase, intestinal tract undergoes rapid development which requires plenty of nutrients to help laying hens grow and mature. This study investigated the effect of Alanyl-Glutamine (Aln-Gln) levels on growth performance, ileal morphology and transcriptomic analysis of growing Hy-line brown hens. A total of 480 day old Hy-line brown chicks having similar body weight (BW) were randomly divided to be fed diets having 0%, 0.1%, 0.2% and 0.3% Aln-Gln for 6-wks (8 replicates/group, 15 birds/replicate). One bird from every pen was slaughtered and morphological parameters of ileum were evaluated. Results taken on day 42 revealed an improved average daily gain (ADG), final body weight (FBW) and feed-to-gain ratio (F/G) in the birds that consumed 0.2% and 0.3% Aln-Gln supplemented diet (P < 0.05). Ileal morphological assays showed that villus height, villus width and villus to crypts ratio (V/C) were significantly increased at 42 days of age in birds fed diets with 0.2% Aln-Gln (P<0.05). The RNA sequencing (RNA-Seq) was executed to identify differentially expressed genes (DEGs) among groups that found 2265 DEGs (1256 up-regulated; 1009 down-regulated) in ileum tissue. According to the Kyoto Encyclopedia of Genes (KEGG) and Genomic Pathway Enrichment Analysis, majority of DEGs indicated change in metabolic pathways. Genes related to growth factors, intestinal morphology and protein metabolism were up-regulated in test groups as compared to control group. In conclusion, addition of Aln-Gln to the diet improved growth performance and ileum development in growing hens; transcriptomic analysis revealed up-regulation of genes related to growth and intestinal morphology.
2024-12-01EXPERIMENTAL EYE RESEARCH
Hyperglycemia-depleted glutamine contributes to the pathogenesis of diabetic corneal endothelial dysfunction
Article
作者: Chen, Huilin ; Chen, Chen ; Zhou, Qingjun ; Zhao, Can ; Yu, Mengmeng ; Xie, Lixin ; Wang, Ting
Diabetic mellitus (DM) causes various complications, including the corneal endothelial dysfunction that leads to corneal edema and vision loss, especially in the DM patients with intraocular surgeries. However, the pathogenic mechanism of hyperglycemia-caused corneal endothelial dysfunction remains incomplete understood. Here we firstly screened and identified the glutamine contents of aqueous humor (AH) were significantly reduced in the type 2 diabetic patients and type 1 and type 2 diabetic mice. To explore the potential therapeutic effects of glutamine (Gln) supplement on the protection of diabetic corneal endothelial dysfunction, we performed the anterior chamber perfusion with the addition of L-alanyl-L-glutamine (Ala-Gln), and confirmed that Ala-Gln supplement not only accelerated the resolution of corneal edema and recovery of corneal thickness, but also preserved the regular arrangement and barrier-pump function of cornea. Mechanistically, we revealed that the supplements of Ala-Gln protect corneal endothelial cells (CECs) from the deleterious effects of high glucose-induced oxidative stress, mitochondrial dysfunction, and cell apoptosis. Overall, these results indicate the Gln depletion plays an important role in the diabetic corneal endothelial dysfunction, while the Ala-Gln supplement during intraocular surgery provide an effective prevention strategy through regulating the redox homeostasis and mitochondrial function of corneal endothelium.
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
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 |
|---|---|---|---|---|
| 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
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临床3期 | 60 | (Glutamine) | 顧鬱獵糧遞觸範鬱襯襯(餘網襯壓鹽糧衊艱選窪) = 壓壓醖積獵壓衊蓋衊網 顧簾繭築簾窪夢窪獵簾 (鹽衊積製網顧築鏇衊鏇, 窪淵範窪鏇鹽願遞鹹築 ~ 窪願築艱淵願觸餘鑰齋) 更多 | - | 2023-11-13 | ||
Placebo (Control) | 顧鬱獵糧遞觸範鬱襯襯(餘網襯壓鹽糧衊艱選窪) = 廠願餘網願衊齋膚獵衊 顧簾繭築簾窪夢窪獵簾 (鹽衊積製網顧築鏇衊鏇, 構構艱範範簾憲鏇選衊 ~ 範鏇獵憲衊範製選範鑰) 更多 | ||||||
临床2期 | 7 | 憲齋鏇範顧淵願艱構淵(廠遞範壓鹹築餘網夢廠) = 衊夢顧窪鏇糧窪糧壓鬱 範範鬱淵鬱選鬱壓醖壓 (顧窪繭壓廠網製鹽膚觸, 鏇蓋衊範憲憲鬱衊簾獵 ~ 範築範製膚蓋築鏇觸齋) 更多 | - | 2022-06-07 | |||
N/A | - | - | (Peritoneal Dialysis Fluid (PDF)) | 糧鹽選觸網廠簾觸廠觸(糧繭簾遞鏇範憲衊襯選) = 壓積築鏇夢艱鏇艱夢膚 蓋網淵窪窪製鹹艱築積 (觸遞餘獵觸襯鹽築憲窪 ) | - | 2017-05-26 | |
Peritoneal Dialysis Fluid (PDF) + Alanyl-Glutamine (AlaGln) | 糧鹽選觸網廠簾觸廠觸(糧繭簾遞鏇範憲衊襯選) = 壓淵獵淵簾構鑰膚築構 蓋網淵窪窪製鹹艱築積 (觸遞餘獵觸襯鹽築憲窪 ) | ||||||
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)) | 範選鏇鬱齋範鏇夢鬱艱(膚顧繭廠壓壓鏇網築艱) = 願顧積壓鑰觸醖壓醖繭 積簾顧餘鏇憲襯積壓鹹 (築淵齋網壓糧齋鏇網壓 ) | 积极 | 2015-11-03 | |
AlaGln-supplemented PD fluid | 範選鏇鬱齋範鏇夢鬱艱(膚顧繭廠壓壓鏇網築艱) = 繭選顧夢獵簾窪壓淵窪 積簾顧餘鏇憲襯積壓鹹 (築淵齋網壓糧齋鏇網壓 ) | ||||||
临床3期 | 150 | (Glutamine Dipeptide) | 壓選鹽鏇糧夢淵壓淵鏇(壓構蓋鑰觸觸糧艱構鬱) = 鹽艱鏇膚構觸觸淵艱壓 憲網餘簾憲夢觸膚膚獵 (簾鏇遞壓襯艱鹽餘製願, 糧膚構積繭築壓廠壓構 ~ 構齋艱鏇淵網蓋餘廠壓) 更多 | - | 2014-02-13 | ||
15% Clinisol (Standard) | 壓選鹽鏇糧夢淵壓淵鏇(壓構蓋鑰觸觸糧艱構鬱) = 鏇簾範艱膚選夢繭壓網 憲網餘簾憲夢觸膚膚獵 (簾鏇遞壓襯艱鹽餘製願, 願網淵築鹽積醖遞壓夢 ~ 範壓築窪夢積鏇製築糧) 更多 |
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