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

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100 项与西地那非/二甲双胍/亮氨酸相关的转化医学

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100 项与西地那非/二甲双胍/亮氨酸相关的专利（医药）

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270

项与西地那非/二甲双胍/亮氨酸相关的文献（医药）

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.

2024-11-01·Journal of Bioscience and Bioengineering

Structural and functional analysis of l-methionine oxidase identified through sequence data mining

Article

作者: Araseki, Hayato ; Kawamura, Yui ; Nakano, Shogo ; Chisuga, Taichi ; Sugiura, Sayaka

l-Amino acid oxidase (LAAO), an FAD-dependent enzyme, catalyzes the oxidation of l-amino acids (l-AAs) to their corresponding imino acids. While LAAOs, which can oxidize charged or aromatic l-AAs specifically, have been extensively characterized across various species, LAAOs that have high specificity toward alkyl-chain l-AAs, such as l-Met, are hardly characterized for now. In this study, we screened a highly specific l-Met oxidizing LAAOs from Burkholderiales bacterium (BbMetOx) and Undibacterium sp. KW1 (UndMetOx) using sequence similarity network (SSN) analysis. These enzymes displayed an order of magnitude higher specific activity towards l-Met compared to other l-AAs. Enzyme activity assays showed that these LAAOs operate optimally at moderate condition because the optimal pH and T_m values were pH 7.0 and 58-60°C. We determined the crystal structures of wild-type BbMetOx (BbMetOx(WT)) and an inactivated mutant, BbMetOx (K304A), at 2.7 Å and 2.2 Å resolution, respectively. The overall structure of BbMetOx is closely similar to other known LAAOs of which structures were determined. Comparative analysis of the BbMetOx structures revealed significant conformational changes in the catalytic domain, particularly a movement of approximately 8 Å in the C_α atom of residue Y180. Further analysis highlighted four residues, i.e., Y180, M182, F300, and M302, as critical for l-Met recognition, with alanine substitution at these positions resulting in loss of activity. This study not only underscores the utility of SSN for discovering novel LAAOs but also advances our understanding of substrate specificity in this enzyme family.

项与西地那非/二甲双胍/亮氨酸相关的新闻（医药）

2022-12-12

·PRNewswire

Propulsion of Nonalcoholic Steatohepatitis Pipeline as Novel and Extensive 150+ Therapies Likely to Enter in the Treatment Domain | DelveInsight

The prevalence of nonalcoholic steatohepatitis has been rising since the past few years, which prompts the growing demand for treatment options. The increasing prevalence of Nonalcoholic Steatohepatitis and the growing research and development activities drive the market. The Companies developing the potential therapies in the last stage of development include Madrigal Pharmaceuticals, Inventiva, Boehringer Ingelheim, and several others. LAS VEGAS, Dec. 12, 2022 /PRNewswire/ -- DelveInsight's ' Nonalcoholic Steatohepatitis Pipeline Insight – 2022 ' report provides comprehensive global coverage of available, marketed, and pipeline nonalcoholic steatohepatitis therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the nonalcoholic steatohepatitis pipeline domain. Key Takeaways from the Nonalcoholic Steatohepatitis Pipeline Report DelveInsight's nonalcoholic steatohepatitis pipeline report depicts a robust space with 130+ active players working to develop 150+ pipeline therapies for nonalcoholic steatohepatitis treatment. Key nonalcoholic steatohepatitis companies such as Madrigal Pharmaceuticals, Intercept Pharmaceuticals, Cirius Therapeutics, Novo Nordisk, Galmed Pharmaceuticals, AstraZeneca, Galectin Therapeutics, Viking Therapeutics, Eli Lilly and Company, Terns Pharmaceuticals, Sinew Pharma, Novartis Pharmaceuticals, Poxel SA, AngioLab, Pfizer, Lipocine, Inc., CytoDyn, Inc., Alnylam Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma, Chemomab Therapeutics, NuSirt Biopharma, HK inno. N, Kowa Pharmaceutical, Ionis Pharmaceuticals, NorthSea Therapeutics, Rivus Pharmaceuticals, Hanmi Pharmaceutical, Hepagene Therapeutics, HighTide Biopharma, Akero Therapeutics, Merck Sharp & Dohme LLC, Cascade Pharmaceuticals, Hepion Pharmaceuticals, Chipscreen Biosciences, Boston Pharmaceuticals, Bristol-Myers Squibb, Sunshine Lake Pharma, GSK plc., Future Medicine, Gilead Sciences, ENYO Pharma, Histogen, and others are evaluating nonalcoholic steatohepatitis drugs to improve the treatment landscape. Promising nonalcoholic steatohepatitis pipeline therapies in various stages of development include TERN-101, SNP-610, LJN452 (tropifexor + licogliflozin), PXL065, ALS-L1023, PF-06865571 + PF-05221304, PF-06835919, PF-06865571, ORMD-0801, Norucholic acid, NNC0194-0499, MN-001, MK-3655, MET642, MET409, LPCN 1144, LIK066, Leronlimab, ALN-HSD, MT-3995, CM101, Leu-Mit-Sil (NS-0200), IN-A010, Efruxifermin (EFX), Efinopegdutide, EDP-305, JKB-122, CS0159 (Linafexor), CRV431, Chiglitazar sodium, BOS-580, BMS-986263, HEC96719, GSK4532990, FM101, Firsocostat, EPY001a, Emricasan, BMS-986036, BIO89-100, BI 456906, BFKB8488A, AXA1125, ASC 41, GS-9674 (Cilofexor), ZSP1601, and others. In November 2022, Sagimet Biosciences announced positive interim data from its Phase IIb clinical trial (FASCINATE-2) with denifanstat, a fatty acid synthase (FASN) inhibitor, in non-alcoholic steatohepatitis patients. Data showed statistically significant improvements across key markers of NASH, reinforcing results observed in earlier studies, including statistically significant reductions in markers of liver fat, inflammation, and fibrosis. There were no treatment-related serious adverse events, with the majority of adverse events mild to moderate in nature (Grade 1 and 2). Additional interim data are expected in early 2023. In November 2022, Inventiva announced that the United States Patent and Trademark Office granted a patent (U.S. Patent No. 11,504,380) that protects the use of lanifibranor for the treatment of cirrhotic patients at risk of progressing from compensated stage to decompensated stage. This patent will expire on November 8, 2039. This patent further expands the intellectual property protection of lanifibranor in the United States for use in patients with cirrhotic NASH. In October 2022, Galectin Therapeutics, Inc. reported the positive outcome of its second data and safety monitoring board (DSMB) meeting for NAVIGATE, its seamless, adaptive, phase IIb/III study of belapectin in patients with liver cirrhosis caused by non-alcoholic steatohepatitis (NASH). The objective of this second independent DSMB was further to review the emerging tolerance and safety profiles of belapectin. Based on its deliberation, the DSMB concluded that NAVIGATE could continue as designed, without modifications. In September 2022, Inventiva and Chia Tai-Tianqing Pharmaceutical Group entered into a licensing and collaboration agreement to develop and commercialize lanifibranor, if approved, for the treatment of nonalcoholic steatohepatitis and potentially other metabolic diseases in mainland China, Hong Kong, Macau, and Taiwan. In June 2022, Poxel SA announced that the U.S. Patent and Trademark Office (PTO) has issued to Poxel US Patent No. 11319313, which represents a new patent for PXL065, a novel, proprietary deuterium-stabilized R-stereoisomer of pioglitazone which is being investigated in Phase II stage of clinical trial evaluation for the treatment of Nonalcoholic steatohepatitis (NASH). In May 2022, Pfizer Inc. announced the U.S. Food and Drug Administration (FDA) had granted Fast Track designation to Pfizer's investigational combination therapy for the treatment of non-alcoholic steatohepatitis (NASH) with liver fibrosis: ervogastat (PF-06865571, a diacylglycerol O-acyltransferase 2 inhibitor, or DGAT2i) and clesacostat (PF-05221304, an acetyl-CoA carboxylase inhibitor, or ACCi). In May 2022, Hepion Pharmaceuticals, Inc. announced that it has entered into a clinical collaboration with HepQuant, a Denver-based, privately held company with novel, proprietary investigational technology for evaluating liver function and health in patients with chronic liver diseases. Hepion will incorporate the HepQuant 'SHUNT' test into a dedicated Phase IIb clinical trial in presumed NASH F3 subjects. In February 2022, the US Food and Drug Administration (FDA) granted a Fast-Track Designation to Axcella Therapeutics' AXA1125 to treat non-alcoholic steatohepatitis (NASH) with liver fibrosis. In January 2022, LISCure Biosciences announced that it had executed a research collaboration agreement with Mayo Clinic for new drug development for rare liver diseases. LISCure Biosciences Inc. has executed a research collaboration agreement with US based-Mayo Clinic for new drug development for rare liver diseases. Request a sample and discover the nash drugs in development 2022 @ Nonalcoholic Steatohepatitis Pipeline 2022 Report The nonalcoholic steatohepatitis pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage nonalcoholic steatohepatitis drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the nonalcoholic steatohepatitis clinical trial landscape. Nonalcoholic Steatohepatitis Overview Nonalcoholic steatohepatitis (NASH) is a type of liver inflammation and damage caused by fat buildup. It is one of several conditions known as nonalcoholic fatty liver disease. Nonalcoholic fatty liver disease is classified into two types: isolated fatty liver, in which only fat accumulates, and nonalcoholic steatohepatitis, in which fat, inflammation, and liver cell damage occur. NASH does not usually cause symptoms. Most people with NASH feel fine and are unaware that they have it. As NASH progresses and liver damage worsens, a patient may experience fatigue, weight loss, general weakness, and acne in the upper right part of the belly. Screening for nonalcoholic fatty liver disease in the general population is not advised. It is usually considered after discovering unexplained liver enzyme levels, or imaging reveals hepatic steatosis. A patient's medical history, a physical exam, and tests for nonalcoholic steatohepatitis are used by doctors. Want to discover how the Nash treatment pipeline will look like? Request for sample @ NASH Drug Pipeline 2022 A snapshot of the Nonalcoholic Steatohepatitis Pipeline Drugs mentioned in the report: Want to know how nash dash the pipeline race is for new agents? Download the sample page @ NASH Clinical Trials Nonalcoholic Steatohepatitis Therapeutics Assessment The nonalcoholic steatohepatitis pipeline report proffers an integral view of nonalcoholic steatohepatitis emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Nonalcoholic Steatohepatitis Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Intravenous, Parenteral, Oral, Subcutaneous Therapeutics Assessment By Molecule Type: Antibody, Biologic, Cell therapy, Peptide, Protein, Small molecule Therapeutics Assessment By Mechanism of Action: Adiponutrin inhibitor, Diacylglycerol O acyltransferase inhibitor, Adiponutrin modulator, RNA interference, Glucagon like peptide 1 receptor agonist, Ornithine decarboxylase stimulant, Farnesoid X-activated receptor agonist, Thyroid hormone receptor beta agonist, Mitochondrial membrane transport protein modulator, Thyroid hormone receptor beta agonists, Peroxisome proliferator-activated receptor alpha agonist Key Nonalcoholic Steatohepatitis Companies:Madrigal Pharmaceuticals, Intercept Pharmaceuticals, Cirius Therapeutics, Novo Nordisk, Galmed Pharmaceuticals, AstraZeneca, Galectin Therapeutics, Viking Therapeutics, Eli Lilly and Company, Terns Pharmaceuticals, Sinew Pharma, Novartis Pharmaceuticals, Poxel SA, AngioLab, Pfizer, Lipocine, Inc., CytoDyn, Inc., Alnylam Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma, Chemomab Therapeutics, NuSirt Biopharma, HK inno. N, Kowa Pharmaceutical, Ionis Pharmaceuticals, NorthSea Therapeutics, Rivus Pharmaceuticals, Hanmi Pharmaceutical, Hepagene Therapeutics, HighTide Biopharma, Akero Therapeutics, Merck Sharp & Dohme LLC, Cascade Pharmaceuticals, Hepion Pharmaceuticals, Chipscreen Biosciences, Boston Pharmaceuticals, Bristol-Myers Squibb, Sunshine Lake Pharma, GSK plc., Future Medicine, Gilead Sciences, ENYO Pharma, Histogen, and others. Key Nonalcoholic Steatohepatitis Pipeline Therapies: TERN-101, SNP-610, LJN452(tropifexor + licogliflozin), PXL065, ALS-L1023, PF-06865571 + PF-05221304, PF-06835919, PF-06865571, ORMD-0801, Norucholic acid, NNC0194-0499, MN-001, MK-3655, MET642, MET409, LPCN 1144, LIK066, Leronlimab, ALN-HSD, MT-3995, CM101, Leu-Mit-Sil (NS-0200), IN-A010, Efruxifermin (EFX), Efinopegdutide, EDP-305, JKB-122, CS0159 (Linafexor), CRV431, Chiglitazar sodium, BOS-580, BMS-986263, HEC96719, GSK4532990, FM101, Firsocostat, EPY001a, Emricasan, BMS-986036, BIO89-100, BI 456906, BFKB8488A, AXA1125, ASC 41, GS-9674 (Cilofexor), ZSP1601, and others. Dive deep into rich insights for nonalcoholic steatohepatitis research; visit @ NASH Treatment Pipeline Table of Contents For further information on the most promising nash drugs, reach out @ NASH Medication Pipeline Related Reports Nonalcoholic Steatohepatitis Epidemiology Nonalcoholic Steatohepatitis Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical, and forecasted nonalcoholic steatohepatitis epidemiology in the 7MM. Nonalcoholic Steatohepatitis Market Nonalcoholic Steatohepatitis Market Insight, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key nonalcoholic steatohepatitis companies, including Boehringer Ingelheim, Oramed Pharmaceuticals, ENYO Pharma, Terns Pharmaceuticals, Cirius Therapeutics, among others. Non-Alcoholic Fatty Liver Disease Market Non-Alcoholic Fatty Liver Disease Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key non-alcoholic fatty liver disease companies including AstraZeneca, Novartis, Pfizer, Roche, among others. Non-Alcoholic Fatty Liver Disease Pipeline Non-Alcoholic Fatty Liver Disease Pipeline Insight – 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key advanced non-alcoholic fatty liver disease companies, including AstraZeneca, Novartis, Pfizer, Roche, among others. Non-Alcoholic Fatty Liver Disease Epidemiology Non-Alcoholic Fatty Liver Disease Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical, and forecasted non-alcoholic fatty liver disease epidemiology in the 7MM. Other Trending Reports Alcohol Use Disorder Market | Liver Cancer Market | Alcoholic Hepatitis - Market | Acute Liver Failure - Market | Liver Angiosarcoma - Market | Liver Cirrhosis - Market | Chronic Liver Disease - Market | Advanced Liver Cancer - Market | Acute On Chronic Liver Failure (ACLF) Market Related Healthcare Services Healthcare Business Consulting Healthcare Competitive Intelligence Services Healthcare Asset Prioritization Services About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. Connect with us at LinkedIn Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research LLP

临床2期引进/卖出快速通道

100 项与西地那非/二甲双胍/亮氨酸相关的药物交易

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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

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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	簾壓醖網衊壓鏇餘糧顧(夢襯願選鹹遞膚膚構網) = 壓繭淵糧製繭繭衊憲蓋齋範構鬱夢顧網醖選襯 (願夢廠網壓築膚鑰艱艱 )	-	2019-01-01
				High dose (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil)	(窪鑰製顧築獵願糧構鹹) = 艱製積簾鹹觸糧獵繭鹽蓋製構鏇遞鏇衊膚餘繭 (衊簾鏇選構構淵齋觸醖 ) 更多
NCT03364335 (CTgov)	临床2期	肥胖	267	Placebo (Placebo)	積鹽窪選糧襯鏇鏇憲築(選齋鬱襯醖鹽構遞膚製) = 衊範獵遞衊鬱襯鹹鑰憲繭築衊鑰餘築糧醖艱顧 (糧觸醖憲醖獵繭範蓋襯, 鏇觸網願餘襯襯網窪遞 ~ 範衊醖襯艱繭願糧鹹願) 更多	-	2018-11-27
				Leu Sil 4.0mg (Leu Sil 1.0mg)	積鹽窪選糧襯鏇鏇憲築(選齋鬱襯醖鹽構遞膚製) = 鏇網夢鑰築齋鑰製襯襯繭築衊鑰餘築糧醖艱顧 (糧觸醖憲醖獵繭範蓋襯, 顧遞壓艱壓鬱積糧糧遞 ~ 夢積積顧鹽醖襯膚襯艱) 更多
NCT02546609 (CTgov)	临床2期	代谢功能障碍相关的脂肪肝病	91	Placebo (Placebo)	鏇網膚顧淵醖簾壓構顧(遞簾糧繭壓簾獵衊觸網) = 繭艱獵範鬱簾積願觸襯衊艱憲鬱遞憲鹹獵製獵 (鬱窪夢構夢齋顧範衊淵, 艱築獵膚簾網壓蓋壓鑰 ~ 製鬱憲夢選獵遞製築繭) 更多	-	2018-05-02
				Leu-Met-Sil 1.0 (Leu Met Sil 0.5mg)	鏇網膚顧淵醖簾壓構顧(遞簾糧繭壓簾獵衊觸網) = 觸簾憲襯觸觸壓範襯壓衊艱憲鬱遞憲鹹獵製獵 (鬱窪夢構夢齋顧範衊淵, 獵簾齋鑰繭襯願願網構 ~ 壓醖齋糧衊鏇齋鏇淵範) 更多