西地那非/二甲双胍/亮氨酸(Sildenafil/Metformin/Leucine) - 药物靶点：PDE5A x PRKAB1_在研适应症：2型糖尿病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Leu-Met-Sil、Leucine/metformin/sildenafil、Leucine/sildenafil/metformin

+ [4]

靶点

PDE5A x PRKAB1

作用机制

PDE5A抑制剂(磷酸二酯酶-5A抑制剂)、PRKAB1激活剂(腺苷酸活化蛋白激酶亚基β1激活剂)

治疗领域

内分泌与代谢疾病

在研适应症

2型糖尿病

非在研适应症

代谢功能障碍相关的脂肪肝病非酒精性脂肪性肝炎肥胖

原研机构

Nusirt Sciences, Inc.

在研机构

Nusirt Sciences, Inc.

非在研机构

NuSirt Biopharma, Inc.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

结构/序列

分子式C28H38N6O11S

InChIKeyDEIYFTQMQPDXOT-UHFFFAOYSA-N

CAS号171599-83-0

查看全部结构式(3)

关联

2

项与西地那非/二甲双胍/亮氨酸相关的临床试验

NCT03364335

/ Completed临床2期

A Randomized, Double-blind, Placebo-controlled Study of Effects of Two Fixed-dose Leucine-sildenafil Combinations (NS-0300) or Two Fixed-dose Leucine-sildenafil-metformin Combinations (NS-0200) Versus Placebo on Body Weight in Obesity

This is a 24-week study to evaluate the effects of two fixed-dose combinations of leucine and sildenafil or two fixed-dose combinations of leucine, sildenafil and metformin compared to placebo. The primary objective of this study is to evaluate the percentage change in body weight in subjects from Baseline/Visit 2 (Day 1) to Study Termination/Visit 8 (Day 168/Week 24).

开始日期2018-01-08

申办/合作机构

NuSirt Biopharma, Inc.

NCT02546609

/ Completed临床2期

A Randomized, Blinded, Placebo-Controlled Study To Evaluate The Effect Fixed-Dose Leucine, Metformin, Sildenafil Combinations(NS-0200) Versus Placebo On Hepatic Fat Assessed By MRI In Non Alcoholic Fatty Liver Disease Patients

The goal of this study is to determine if NS-0200 can reduce the amount of liver fat in patients diagnosed with non-alcoholic fatty liver disease (NAFLD). This study will compare two doses of NS-0200 to placebo in NAFLD patients.

开始日期2015-11-19

申办/合作机构

NuSirt Biopharma, Inc.

100 项与西地那非/二甲双胍/亮氨酸相关的临床结果

登录后查看更多信息

100 项与西地那非/二甲双胍/亮氨酸相关的转化医学

登录后查看更多信息

100 项与西地那非/二甲双胍/亮氨酸相关的专利（医药）

登录后查看更多信息

281

项与西地那非/二甲双胍/亮氨酸相关的文献（医药）

2025-03-01·Journal of Pharmaceutical and Biomedical Analysis

Dynamic profiling of intra- and extra-cellular L/D-amino acids metabolism in colorectal cell and intestinal epithelial cell

Article

作者: Sun, Cuirong ; Deng, Wenchan ; Pan, Yuanjiang ; Huang, Rongrong

The metabolism process of amino acids is closely related to the growth of normal and cancer cells. It is still not clear how L/D-configuration amino acids participate in the metabolism of colorectal cell. Herein, intra- and extra-cellular metabolic distribution of L/D-amino acids in colorectal cell (HCT116) and human normal intestinal epithelial cell (NCM460) were profiled utilizing HPLC-MS/MS coupled with a chiral probe. The results displayed the differential metabolic portrayal for the two cell lines. Compared with NCM460 cell, 13 kinds of significant differential amino acids were founded in a lower concentration within HCT116 cell, and L-Gln was even not detected for intra-cell; as for extra-cell culture medium, the HCT116 cell consumed more L-Gln, D-Phe and D-Leu, while L-Met was low ingested in HCT116 cell. L-Ala and Gly were excretion in both two cell lines, excepted L-Cit which was uptake in HCT116 and excretion in NCM460 cell. Furthermore, the dynamic changes of chiral amino acids displayed that phenylalanine, tyrosine and tryptophan biosynthesis and arginine biosynthesis is the major pathway for intra-cellular metabolites and extra-cellular metabolites, respectively. Moreover, with additional D-amino acids in culture medium, the results exhibited that high concentration of D-amino acids have no significant effect on the proliferation of NCM460 cell, but could influence the profiling of amino acids metabolites, and further affect the proliferation of HCT116 cell. This present work enhances the understanding of these differential amino acids metabolic network and depicts a dynamic process of metabolic dysregulation of HCT116 and NCM460 cell.

2024-12-01·Poultry Science

Relative bioavailability of L-methionine and DL-methionine in growing broilers

Article

作者: Izadi, Elham ; Torshizi, Mohammad Amir Karimi ; Shahir, Mohammad Hossein

Two separate studies were conducted in growing broiler chickens to examine the relative bioavailability (RBA) of L-smethionine (L-Met) vs. DL-methionine (DL-Met) in the starter (0-10 d, Experiment 1) and grower (11-24 d, Experiment 2) periods. In each experiment, 540 male Arian broilers were weighed and randomly allocated to nine dietary treatments in a completely randomized design with 6 replicates: basal diet (BD) with no methionine (Met) supplementation and eight diets supplemented with incremental levels (0.8, 1.6, 2.4, and 3.2 g/kg) of DL-methionine (DL-Met) or L-methionine (L-Met). Supplementation of the BD with either DL-Met or L-Met improved growth performance (P < 0.05), breast percentage (P < 0.05), and antioxidant status (P < 0.05) of broilers in both experiments. Orthogonal contrasts showed that L-Met supplementation compared to DL-Met (specifically at levels 0.8 and 1.6 g/kg) improved average daily gain (ADG, P < 0.05), average daily feed intake (ADFI, P < 0.01), and feed to gain ratio (F:G, P < 0.01) in the starter phase. In the grower phase, L-Met supplementation (specifically at levels 0.8 and 1.6 g/kg) only improved F:G (P < 0.05) compared to DL-Met, with no significant differences in the other performance parameters. Nonlinear regression analysis showed that RBA of L-Met based on carcass percentage was significantly (P < 0.05) higher than that of DL-Met in the starter phase. Based on the findings of this study, it seems that using L-Met compared to DL-Met may improve the feed efficiency and carcass percentage of young growing broiler chickens.

2024-12-01·Biofilm

d-Methionine-induced DNases disperse established Burkholderia pseudomallei biofilms and promotes ceftazidime susceptibility

Article

作者: Chareonsudjai, Sorujsiri ; Pakkulnan, Rattiyaphorn ; Sirichoat, Auttawit

Burkholderia pseudomallei biofilm is correlated with pathogenesis, antibiotic resistance, and relapsing cases of melioidosis, leading to challenges in clinical management. There is increasing interest in employing biofilm dispersal agents as adjunctive treatments for biofilm-associated infections. Methionine (Met) has shown promise as an anti-biofilm agent by inducing bacterial DNase production, resulting in the degradation of extracellular DNA (eDNA) and dispersion of bacterial biofilm. In this study, we investigated the impact of 0.05-50 μM D-Met and L-Met on the 24-h established biofilm of a clinical isolate, B. pseudomallei H777. Our findings revealed the ability of D-Met and L-Met to disperse the established biofilm in a non-dose-dependent manner accompanied by eDNA depletion. Real-time PCR analysis further identified an up-regulation of bacterial nuclease genes, including recJ, eddB, nth, xth, and recD, in the presence of 0.05 μM D-Met. Similarly, recJ and eddB in B. pseudomallei were up-regulated in response to the presence of 0.05 μM L-Met. Notably, D-Met enhanced the susceptibility of B. pseudomallei H777 biofilm cells to ceftazidime. Our findings indicate a correlation between methionine supplementation and the up-regulation of nuclease genes, leading to eDNA depletion and the dispersal of preformed B. pseudomallei H777 biofilm. This enhances the susceptibility of biofilm cells to ceftazidime, showing promise in combating biofilm-associated B. pseudomallei infections.

100 项与西地那非/二甲双胍/亮氨酸相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床2期	-	Nusirt Sciences, Inc.	-
肥胖	药物发现	美国	NuSirt Biopharma, Inc.	2018-01-08
代谢功能障碍相关的脂肪肝病	药物发现	美国	NuSirt Biopharma, Inc.	2015-11-19
非酒精性脂肪性肝炎	药物发现	美国	Nusirt Sciences, Inc.	2015-11-19

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02546609 (Pubmed)	临床2期	代谢功能障碍相关的脂肪肝病	91	Placebo	構膚築憲餘淵壓餘夢廠(獵夢襯憲齋窪醖顧繭夢) = 鏇觸願餘製鬱構襯壓壓淵齋齋遞艱鏇醖願顧獵 (積願鏇艱壓願憲淵遞鬱 )	-	2019-01-01
				High dose (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil)	(膚簾鬱鏇淵壓淵艱齋簾) = 艱淵鑰範願繭築齋網糧廠獵廠壓鏇選膚鹹簾鏇 (鹽窪遞鑰鬱糧獵鬱遞蓋 ) 更多
NCT03364335 (CTgov)	临床2期	肥胖	267	Placebo (Placebo)	襯遞糧鬱網壓鏇鏇獵齋(鏇築簾遞憲糧鏇襯範糧) = 願廠鹽衊鏇鬱齋鬱繭繭鑰鬱範遞淵繭衊糧憲衊 (艱網鏇遞築夢獵廠繭廠, 壓襯觸構窪窪築構製膚 ~ 範襯鬱襯網壓鹹範鏇襯) 更多	-	2018-11-27
				Leu Sil 4.0mg (Leu Sil 1.0mg)	襯遞糧鬱網壓鏇鏇獵齋(鏇築簾遞憲糧鏇襯範糧) = 憲觸淵鹹鬱醖齋壓顧製鑰鬱範遞淵繭衊糧憲衊 (艱網鏇遞築夢獵廠繭廠, 鹹夢網膚構糧窪壓窪觸 ~ 艱夢鹹鏇鏇願積夢憲餘) 更多
NCT02546609 (CTgov)	临床2期	代谢功能障碍相关的脂肪肝病	91	Placebo (Placebo)	鏇鏇糧顧遞鹹廠鹽簾淵(襯鹽獵膚衊壓餘網壓顧) = 遞選廠憲夢衊餘壓襯網繭鑰憲壓觸夢獵廠遞鑰 (廠鬱窪夢餘廠鹹鬱襯廠, 鹹積遞築鑰簾窪衊醖繭 ~ 鑰觸選衊願範鑰蓋觸網) 更多	-	2018-05-02
				Leu-Met-Sil 1.0 (Leu Met Sil 0.5mg)	鏇鏇糧顧遞鹹廠鹽簾淵(襯鹽獵膚衊壓餘網壓顧) = 憲遞鏇鑰膚蓋繭積淵鹽繭鑰憲壓觸夢獵廠遞鑰 (廠鬱窪夢餘廠鹹鬱襯廠, 醖鬱選製齋遞廠餘淵鏇 ~ 願膚製憲窪鬱願鑰築醖) 更多