Peg-IFN-alfa 2b/Ribavirin/Vaniprevir therapy for chronic hepatitis C: Effectiveness prediction by gene analysis and duration of therapy - Peg-IFN-alfa 2b/Ribavirin/Vaniprevir therapy for chronic hepatitis C: Effectiveness prediction by gene analysis and duration of therapy

Start Date01 Feb 2015

Sponsor / Collaborator

Kanazawa University

NCT01678131

/ CompletedPhase 1

A Randomized Clinical Trial Using Fine Needle Aspiration For Evaluation of Hepatic Pharmacokinetics of MK-7009 in Chronic Hepatitis C Patients

This study will evaluate the technical feasibility of using fine needle aspiration (FNA) of liver tissue to obtain vaniprevir (MK-7009) liver pharmacokinetic (PK) data, working towards identifying a minimally invasive, reproducible platform to measure liver PK. The study will be done in 2 parts. In Part 1, participants will be randomized to one of five FNA/core needle biopsy (CNB) time-point collection sequences. In Part 2, participants will be randomized to one of two possible doses of vaniprevir and will be assigned to one of five FNA/CNB time-point collection sequences; participants in Part 2 will also receive background therapy with pegylated interferon alpha-2b (Peg-IFN alpha-2b) and ribavirin (RBV). The primary hypothesis is that there is a greater than 80% posterior probability that vaniprevir concentrations are successfully obtained at least 60% of the time from FNA liver samples collected at 2 of 3 specified timepoints.

Start Date30 Oct 2012

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT01405560

/ CompletedPhase 3

A Phase III Study to Evaluate the Safety, Tolerability, and Efficacy of MK-7009 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Japanese Patients With Chronic Hepatitis C Infection Who Were Non-responders to Previous Treatment

The purpose of this study is to evaluate the safety, tolerability, and efficacy of vaniprevir (300 mg twice daily) given in combination with pegylated interferon alfa-2b (peg-IFN) and ribavirin (RBV) in Japanese participants with chronic hepatitis C (CHC) genotype (GT) 1 who have not responded to previous treatment. The primary efficacy objective is to estimate efficacy of vaniprevir, peg-IFN and RBV for 24 weeks as assessed by the percentage of participants achieving undetectable Hepatitis C Virus ribonucleic acid (HCV RNA) 24 weeks after completion of all study therapy (Sustained Viral Response 24 [SVR24]).

Start Date02 Sep 2011

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

100 Clinical Results associated with Vaniprevir

100 Translational Medicine associated with Vaniprevir

100 Patents (Medical) associated with Vaniprevir

119

Literatures (Medical) associated with Vaniprevir

01 Jun 2023·Bioorganic Chemistry

Green and efficient one-pot three-component synthesis of novel drug-like furo[2,3-d]pyrimidines as potential active site inhibitors and putative allosteric hotspots modulators of both SARS-CoV-2 MPro and PLPro

Article

Author: Zeynizadeh, Behzad ; Rimaz, Mehdi ; Mousavi, Hossein

In this paper, an environmentally benign, convenient, and efficient one-pot three-component reaction has been developed for the regioselective synthesis of novel 5-aroyl(or heteroaroyl)-6-(alkylamino)-1,3-dimethylfuro[2,3-d]pyrimidine-2,4(1H,3H)-diones (4a‒n) through the sequential condensation of aryl(or heteroaryl)glyoxal monohydrates (1a‒g), 1,3-dimethylbarbituric acid (2), and alkyl(viz. cyclohexyl or tert-butyl)isocyanides (3a or 3b) catalyzed by ultra-low loading ZrOCl₂•8H₂O (just 2 mol%) in water at 50 ˚C. After synthesis and characterization of the mentioned furo[2,3-d]pyrimidines (4a‒n), their multi-targeting inhibitory properties were investigated against the active site and putative allosteric hotspots of both SARS-CoV-2 main protease (M^Pro) and papain-like protease (PL^Pro) based on molecular docking studies and compare the attained results with various medicinal compounds which approximately in three past years were used, introduced, and or repurposed to fight against COVID-19. Furthermore, drug-likeness properties of the mentioned small heterocyclic frameworks (4a‒n) have been explored using in silico ADMET analyses. Interestingly, the molecular docking studies and ADMET-related data revealed that the novel series of furo[2,3-d]pyrimidines (4a‒n), especially 5-(3,4-methylendioxybenzoyl)-6-(cyclohexylamino)-1,3-dimethylfuro[2,3-d]pyrimidine-2,4(1H,3H)-dione (4g) as hit one is potential COVID-19 drug candidate, can subject to further in vitro and in vivo studies. It is worthwhile to note that the protein-ligand-type molecular docking studies on the human body temperature-dependent M^Pro protein that surprisingly contains zinc^II (Zn^II) ion between His41/Cys145 catalytic dyad in the active site, which undoubtedly can make new plans for designing novel SARS-CoV-2 M^Pro inhibitors, is performed for the first time in this paper, to the best of our knowledge.

22 Sep 2022·Journal of Biomolecular Structure and Dynamics

Targeting allosteric pockets of SARS-CoV-2 main protease M^pro

Article

Author: Bhat, Zahoor Ahmad ; Chitara, Dheeraj ; Madhumalar, Arumugam ; Iqbal, Jawed ; Sanjeev, B. S.

Repurposing of antivirals is an attractive therapeutic option for the treatment of COVID-19. Main protease (M^pro⁾, also called 3 C-like protease (3CL^pro) is a key protease of SARS-CoV-2 involved in viral replication, and is a promising drug target for antivirals. A major challenge to test the efficacy of antivirals is the conformational plasticity of M^pro and its future mutation prone flexibility. Suitable choice of drugs in catalytic and allosteric pockets appear to be essential for combination therapy. Current study, based on docking and extensive set of MD simulations, finds the combination of Elbasvir, Glecaprevir and Ritonavir to be a viable candidate for further experimental drug testing/pharmacophore design for M^pro.Communicated by Ramaswamy H. Sarma.

01 Dec 2021·Bioorganic & Medicinal ChemistryQ3 · MEDICINE

The reorganization energy of compounds upon binding to proteins, from dynamic and solvated bound and unbound states

Q3 · MEDICINE

Article

Author: Foloppe, Nicolas ; Chen, I-Jen

The intramolecular reorganization energy (ΔE_Reorg) of compounds upon binding to proteins is a component of the binding free energy, which has long received particular attention, for fundamental and practical reasons. Understanding ΔE_Reorg would benefit the science of molecular recognition and drug design. For instance, the tolerable strain energy of compounds upon binding has been elusive. Prior studies found some large ΔE_Reorg values (e.g. > 10 kcal/mol), received with skepticism since they imply excessive opposition to binding. Indeed, estimating ΔE_Reorg is technically difficult. Typically, ΔE_Reorg has been approached by taking two energy-minimized conformers representing the bound and unbound states, and subtracting their conformational energy. This is a drastic oversimplification, liable to conformational collapse of the unbound conformer. Instead, the present work applies extensive molecular dynamics (MD) and the modern OPLS3 force-field to simulate compounds bound and unbound states, in explicit solvent under physically relevant conditions. The thermalized unbound compounds populate multiple conformations, not reducible to one or a few energy-minimized conformers. The intramolecular energies in the bound and unbound states were averaged over pertinent conformational ensembles, and the reorganization enthalpy upon binding (ΔH_Reorg) deduced by subtraction. This was applied to 76 systems, including 43 approved drugs, carefully selected for i) the quality of the bioactive X-ray structures and ii) the diversity of the chemotypes, their properties and protein targets. It yielded comparatively low ΔH_Reorg values (median = 1.4 kcal/mol, mean = 3.0 kcal/mol). A new finding is the observation of negative ΔH_Reorg values. Indeed, reorganization energies do not have to oppose binding, e.g. when intramolecular interactions stabilize preferentially the bound state. Conversely, even with competing water molecules, intramolecular interactions can occur predominantly in the unbound compound, and be replaced by intermolecular counterparts upon protein binding. Such disruption of intramolecular interactions upon binding gives rise to occasional larger ΔH_Reorg values. Such counterintuitive larger ΔH_Reorg values may be rationalized as a redistribution of interactions upon binding, qualitatively compatible with binding.

News (Medical) associated with Vaniprevir

21 Jun 2024

·www.biospace.com

Aprea Therapeutics to Host Virtual KOL Event on APR-1051, a Highly Selective and Potentially Best-in-Class Oral WEE1 Inhibitor, on Monday, June 24, 2024

DOYLESTOWN, Pa., June 21, 2024 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE) (“Aprea”, or the “Company”), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, today announced that it will host a virtual KOL event to discuss APR-1051, a highly selective and potentially best-in-class oral WEE1 inhibitor, on Monday, June 24, 2024 at 9:00 AM ET. To register, click here. The webinar will feature Joseph Vacca, PhD, Medicinal Chemistry Expert and Consultant to Aprea, who will discuss the medicinal chemistry history, highly selective drug design, and preclinical findings of APR-1051. It will also feature Eric J. Brown, PhD (University of Pennsylvania) who will discuss preclinical findings across the WEE1 inhibitor class. WEE1 is an enzyme involved in the DNA damage response pathway and is a validated oncology target. APR-1051 is a potent and selective small molecule that has been designed to limit off-target toxicity. Aprea recently initiated the Phase 1 ACESOT-1051 trial evaluating APR-1051 as monotherapy treatment in patients with significant unmet medical need, including patients with Cyclin E over expression. A live question and answer session will follow the formal presentations. Joseph Vacca, PhD is a medicinal chemist who spent 30 years at Merck Research Laboratories (1981 to 2011). He and his teams made major contributions to several approved drugs including the HIV protease inhibitor CRIXIVAN™ (indinavir sulfate), the HIV integrase inhibitor Isentress™ (raltegravir); the HCV protease Inhibitor (Vanihep™, vaniprevir), the combination product Zepatier™ which is a combination of the second generation HCV protease Inhibitor grazoprevir and the NS5A protein Inhibitor elbasvir and the recently approved second generation HIV NNRTI inhibitor doravirine. Upon his retirement from Merck in 2011, Dr. Vacca took a role as Senior Vice President of Early Success Sharing Partnerships at WuXi AppTec Limited. He left WuXi in September 2015 to be a consultant and now acts as an interim head of chemistry for several small startup companies. Dr. Vacca has over 100 publications and patents and is the holder of many awards including a Merck Directors Award (1998); PhRMA Discoverers Award (1999); Intellectual Property Owners “National Inventor of the year Award” (1997); European Inventor of the Year (non-EU nation) (2007); ACS “Award for Creative Invention” (1999); and was a named a Merck Research Laboratories Presidential Fellow in 2008. He was named to the American Chemical Society Medicinal Chemistry Hall of Fame (Aug. 2012) and was also named a “Hero of Chemistry” (along with the research team) for his role in the discovery and development of the HIV integrase inhibitorIsentress™. Dr. Vacca earned a BS in chemistry in 1977 from St. John Fisher College, Rochester, New York, and obtained a PhD degree in Organic Chemistry under Professor Peter T. Lansbury Sr. at the State University of New York at Buffalo (New York). Eric J. Brown, PhD is Associate Professor of Cancer Biology at the University of Pennsylvania and a Scientific Consultant to Aprea Therapeutics. Dr. Brown’s laboratory at Penn focuses on the role of the replication stress response on genome stability. His research seeks to identify the cancer-associated genetic changes that increase the efficacy of therapeutics that abrogate replication stress responses, such as ATR and WEE1 inhibitors. The genetic changes that impact sensitivity to these therapies are identified through various orthogonal approaches, including proteomics, genome-wide breakpoint mapping, and computational methods. Overall, the goal of this research is both to better understand the mechanism by which these cancer therapeutics operate and to improve responses to these treatments in patients. About Aprea Aprea Therapeutics, Inc. is a clinical-stage biopharmaceutical company headquartered in Doylestown, Pennsylvania, focused on precision oncology through synthetic lethality. The Company’s lead program is ATRN-119, a clinical-stage small molecule ATR inhibitor in development for solid tumor indications. APR-1051, an oral, small molecule WEE1 inhibitor, recently entered the clinic. For more information, please visit the company website at . The Company may use, and intends to use, its investor relations website at as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Forward-Looking Statement Certain information contained in this press release includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended related to our study analyses, clinical trials, regulatory submissions, and projected cash position. We may, in some cases use terms such as “future,” “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “targeting,” “confidence,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team and on information currently available to management that involve risks, potential changes in circumstances, assumptions, and uncertainties. All statements contained in this press release other than statements of historical fact are forward-looking statements, including statements regarding our ability to develop, commercialize, and achieve market acceptance of our current and planned products and services, our research and development efforts, including timing considerations and other matters regarding our business strategies, use of capital, results of operations and financial position, and plans and objectives for future operations. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including, without limitation, risks related to the success, timing, and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including our ability to fully fund our disclosed clinical trials, which assumes no material changes to our currently projected expenses), futility analyses, presentations at conferences and data reported in an abstract, and receipt of interim or preliminary results (including, without limitation, any preclinical results or data), which are not necessarily indicative of the final results of our ongoing clinical trials, our understanding of product candidates mechanisms of action and interpretation of preclinical and early clinical results from its clinical development programs, and the other risks, uncertainties, and other factors described under “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in the documents we the U.S. Securities and Exchange Commission. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to update such forward-looking statements for any reason, except as required by law. Investor Contact: Mike Moyer LifeSci Advisors mmoyer@lifesciadvisors.com

Phase 1Executive Change

30 Apr 2021

·www.biospace.com

Research Roundup: Underlying Conditions, COVID-19 Severity and More

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones. More Data on Underlying Conditions and COVID-19 Severity A study out of RCSI University of Medicine and Health Sciences and the HSE Health Protection Surveillance Centre (HPSC) in Ireland has further defined the association between comorbidities and poor outcomes with COVID-19. The study took place between March and July 2020 and collected national data in Ireland from both hospital and community settings. It collected data for almost 20,000 confirmed cases of COVID-19. The results were published in The Lancet Regional Health – Europe. Of the patients studied, there were 1,476 deaths, 2,811 hospitalizations, and 438 ICU admissions. The conditions that carried the most risk were chronic heart disease, a chronic neurological condition, chronic kidney disease and cancer. Morbid obesity was also identified as being associated with severe outcomes. “Previous studies conducted have suggested that specific underlying conditions influence adverse health outcomes among those with a confirmed diagnosis of COVID-19,” said Kathleen Bennett, associate professor in Biostatistics, RCSI. “However, the majority of these studies have focused on hospital-based or local populations only. This study is the first population-based research to capture data across all settings in Ireland, including both community and hospital settings and so it gives us a better picture of the impact of the disease on patients at the population level.” Gilead’s Remdesivir Plus Hep C Drugs Effective Against COVID-19 Researchers with Mount Sinai Hospital and Mount Sinai School of Medicine tested a combination of Gilead’s remdesivir, an antiviral drug, with repurposed drugs for hepatitis C virus (HCV). The combinations, they found, were 10-times more effective at inhibiting SARS-CoV-2, the virus behind COVID-19. Four HCV drugs in combination with remdesivir improved the efficacy of remdesivir. They were simeprevir, vaniprevir, paritaprevir, and grazoprevir. The research group tested 10 HCV drugs, some already approved by the U.S. Food and Drug Administration (FDA). They utilized a supercomputer to model how drugs bind to viral proteins and predicted that those 10 would bind tightly to the SARS-CoV-2 Main protease (Mpro). They also found that seven of the drugs inhibited the SARS-CoV-2 protease. They then tested the seven drugs in monkey and human cells in culture. Four of the HCV drugs inhibited a different SARS-CoV-2 protease called PLpro. It was the four drugs that targeted PLpro that increased the efficacy of remdesivir by as much as 10-fold. While remdesivir must be dosed intravenously, the four HCV drugs are oral. Type 2 Diabetes Associated with Muscle Gene Researchers at Lund University found that in type 2 diabetes, a specific gene related to muscle cells is less active than it is in other people. The gene, VPS39, is important for when muscle cells absorb sugar from blood and build new muscle. In type 2 diabetes, the body’s ability to generate insulin is impaired, resulting in chronically increased blood sugar. The muscles are generally worse at absorbing sugar from food, and this muscle function and strength are typically impaired in type 2 diabetic patients. Their study, which was on muscle stem cells in type 2 diabetes patients compared to healthy controls, found that there were more than twice as many epigenetic changes in the type 2 diabetes group during the differentiation from muscle stem cell to mature muscle cells. Muscle-specific genes were not regulated normally, and epigenetics did not appear to function in the same way in cells from people with type 2 diabetes did. How Brain Cells in Alzheimer’s Patients Lose Their Identity Investigators with the Salk Institute grew neurons that resemble better than ever before the brain cells in older patients. It appears to have given them insight into how the brain cells go off-track in Alzheimer’s patients, losing their cellular identity. The brain cells were characterized by markers of stress in addition to changes where the cells become less specialized. This is similar to what has been observed in cancer cells. The researchers collected skin cells from 13 sporadic, age-related Alzheimer’s patients, as well as cells from three people with the rarer, inherited form of Alzheimer’s. Their controls were skin cells from 19 people age-matched but without Alzheimer’s. Using fibroblasts, they induced neurons, then compared the molecular differences in the cells. They found that the cells from people with Alzheimer’s had specific characteristics different from the healthy control cells. The Alzheimer’s cells lacked synaptic structures, which are vital to sending signals to each other. There were also changes in signaling pathways, which control cell function, an indication the cells were under stress. They also found that the induced Alzheimer’s neurons had similar molecular signatures to immature nerve cells found in the developing brain. What this was interpreted to mean was the Alzheimer’s-based cells had lost their mature identity. A New Anti-Aging Compound Scientists at Washington University School of Medicine found a natural compound, nicotinamide mononucleotide (NMN), that in earlier studies seemed to counteract aging and improved metabolic health in mice, also had positive clinical effects in people. They conducted a clinical trial of postmenopausal women with prediabetes. They demonstrated that NMN improved the ability of insulin to increase glucose uptake in skeletal muscle. This ability is often abnormal in obese, prediabetic or type 2 diabetics. NMN improved expression of genes involved in muscle structure are remodeling. However, it did not lower blood sugar levels, blood pressure, improve blood lipids, increase insulin sensitivity in the liver, reduce fat in the liver or decrease circulating markers of inflammation as was observed in mice. “Although our study shows a beneficial effect of NMN in skeletal muscle, it is premature to make any clinical recommendations based on the results from our study,” said Samuel Klein, senior investigator and the William H. Danforth Professor of Medicine and Nutritional Science and director of the Center for Human Nutrition. “Normally, when a treatment improves insulin sensitivity in skeletal muscle, as is observed with weight loss or some diabetes medications, there also are related improvement in other markers of metabolic health, which we did not detect in our study participants.”

29 Apr 2021

·www.biospace.com

Research Roundup: Underlying Conditions, COVID-19 Severity and More

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones. Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones. More Data on Underlying Conditions and COVID-19 Severity A study out of RCSI University of Medicine and Health Sciences and the HSE Health Protection Surveillance Centre (HPSC) in Ireland has further defined the association between comorbidities and poor outcomes with COVID-19. The study took place between March and July 2020 and collected national data in Ireland from both hospital and community settings. It collected data for almost 20,000 confirmed cases of COVID-19. The results were published in The Lancet Regional Health – Europe . Of the patients studied, there were 1,476 deaths, 2,811 hospitalizations, and 438 ICU admissions. The conditions that carried the most risk were chronic heart disease, a chronic neurological condition, chronic kidney disease and cancer. Morbid obesity was also identified as being associated with severe outcomes. “Previous studies conducted have suggested that specific underlying conditions influence adverse health outcomes among those with a confirmed diagnosis of COVID-19,” said Kathleen Bennett, associate professor in Biostatistics, RCSI. “However, the majority of these studies have focused on hospital-based or local populations only. This study is the first population-based research to capture data across all settings in Ireland, including both community and hospital settings and so it gives us a better picture of the impact of the disease on patients at the population level.” Gilead’s Remdesivir Plus Hep C Drugs Effective Against COVID-19 Researchers with Mount Sinai Hospital and Mount Sinai School of Medicine tested a combination of Gilead’s remdesivir, an antiviral drug, with repurposed drugs for hepatitis C virus (HCV). The combinations, they found, were 10-times more effective at inhibiting SARS-CoV-2, the virus behind COVID-19. Four HCV drugs in combination with remdesivir improved the efficacy of remdesivir. They were simeprevir, vaniprevir, paritaprevir, and grazoprevir. The research group tested 10 HCV drugs, some already approved by the U.S. Food and Drug Administration (FDA). They utilized a supercomputer to model how drugs bind to viral proteins and predicted that those 10 would bind tightly to the SARS-CoV-2 Main protease (Mpro). They also found that seven of the drugs inhibited the SARS-CoV-2 protease. They then tested the seven drugs in monkey and human cells in culture. Four of the HCV drugs inhibited a different SARS-CoV-2 protease called PLpro. It was the four drugs that targeted PLpro that increased the efficacy of remdesivir by as much as 10-fold. While remdesivir must be dosed intravenously, the four HCV drugs are oral. Type 2 Diabetes Associated with Muscle Gene Researchers at Lund University found that in type 2 diabetes, a specific gene related to muscle cells is less active than it is in other people. The gene, VPS39, is important for when muscle cells absorb sugar from blood and build new muscle. In type 2 diabetes, the body’s ability to generate insulin is impaired, resulting in chronically increased blood sugar. The muscles are generally worse at absorbing sugar from food, and this muscle function and strength are typically impaired in type 2 diabetic patients. Their study, which was on muscle stem cells in type 2 diabetes patients compared to healthy controls, found that there were more than twice as many epigenetic changes in the type 2 diabetes group during the differentiation from muscle stem cell to mature muscle cells. Muscle-specific genes were not regulated normally, and epigenetics did not appear to function in the same way in cells from people with type 2 diabetes did. How Brain Cells in Alzheimer’s Patients Lose Their Identity Investigators with the Salk Institute grew neurons that resemble better than ever before the brain cells in older patients. It appears to have given them insight into how the brain cells go off-track in Alzheimer’s patients, losing their cellular identity. The brain cells were characterized by markers of stress in addition to changes where the cells become less specialized. This is similar to what has been observed in cancer cells. The researchers collected skin cells from 13 sporadic, age-related Alzheimer’s patients, as well as cells from three people with the rarer, inherited form of Alzheimer’s. Their controls were skin cells from 19 people age-matched but without Alzheimer’s. Using fibroblasts, they induced neurons, then compared the molecular differences in the cells. They found that the cells from people with Alzheimer’s had specific characteristics different from the healthy control cells. The Alzheimer’s cells lacked synaptic structures, which are vital to sending signals to each other. There were also changes in signaling pathways, which control cell function, an indication the cells were under stress. They also found that the induced Alzheimer’s neurons had similar molecular signatures to immature nerve cells found in the developing brain. What this was interpreted to mean was the Alzheimer’s-based cells had lost their mature identity. A New Anti-Aging Compound Scientists at Washington University School of Medicine found a natural compound, nicotinamide mononucleotide (NMN), that in earlier studies seemed to counteract aging and improved metabolic health in mice, also had positive clinical effects in people. They conducted a clinical trial of postmenopausal women with prediabetes. They demonstrated that NMN improved the ability of insulin to increase glucose uptake in skeletal muscle. This ability is often abnormal in obese, prediabetic or type 2 diabetics. NMN improved expression of genes involved in muscle structure are remodeling. However, it did not lower blood sugar levels, blood pressure, improve blood lipids, increase insulin sensitivity in the liver, reduce fat in the liver or decrease circulating markers of inflammation as was observed in mice. “Although our study shows a beneficial effect of NMN in skeletal muscle, it is premature to make any clinical recommendations based on the results from our study,” said Samuel Klein, senior investigator and the William H. Danforth Professor of Medicine and Nutritional Science and director of the Center for Human Nutrition. “Normally, when a treatment improves insulin sensitivity in skeletal muscle, as is observed with weight loss or some diabetes medications, there also are related improvement in other markers of metabolic health, which we did not detect in our study participants.”

Clinical ResultOligonucleotide

100 Deals associated with Vaniprevir

External Link

KEGG	Wiki	ATC	Drug Bank
D09987	Vaniprevir	J05AP	DB11929

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatitis C	Japan	Merck Sharp & Dohme Corp.	26 Sep 2014

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C	Phase 2	South Korea	Merck GmbH	-
Hepatitis C	Phase 2	Austria	Merck GmbH	-
Hepatitis C	Phase 2	United States	Merck GmbH	-
Hepatitis C	Phase 2	Belgium	Merck GmbH	-
Hepatitis C	Phase 2	Poland	Merck GmbH	-
Hepatitis C	Phase 2	Sweden	Merck GmbH	-
Hepatitis C	Phase 2	France	Merck GmbH	-
Hepatitis C	Phase 2	Lithuania	Merck GmbH	-
Hepatitis C	Phase 2	Spain	Merck GmbH	-
Hepatitis C, Chronic	Phase 1	-	Merck Sharp & Dohme Corp.	27 Jun 2011

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01405560 \| NCT01405937 (Pubmed \| J Gastroenterol Hepatol)	Phase 3	Hepatitis C	-	Vaniprevir + peginterferon alfa-2b + ribavirin (12-week arm)	(oyqjawakjb) = ejkisaxieg erdpdfbgcd (pamvyoqsqo )	-	01 Oct 2016
				Vaniprevir + peginterferon alfa-2b + ribavirin (24-week arm)	(oyqjawakjb) = brotkhvmtt erdpdfbgcd (pamvyoqsqo )
NCT01370642 (7009-043, Pubmed \| J Gastroenterol)	Phase 3	Hepatitis C	294	Vaniprevir plus PR for 12 weeks then PR alone for 12 weeks	(sgozrkecqy) = vrxqazfqnf vuhavtakvi (zabccoteap )	Positive	01 Apr 2016
				Vaniprevir plus PR for 24 weeks	(sgozrkecqy) = elsaiybcjp vuhavtakvi (zabccoteap )
NCT00880763 (Pubmed \| J Gastroenterol)	Phase 2	Hepatitis C	90	Vaniprevir 100 mg	(ebhfpqefhr) = jehcttsydl refbgkoccy (dfinktrkmb ) View more	-	01 Feb 2015
				Vaniprevir 300 mg	(ebhfpqefhr) = ipywkvhmqq refbgkoccy (dfinktrkmb ) View more
NCT01405937 (CTgov)	Phase 3	Hepatitis C, Chronic	51	peg-IFN+ribavirin+vaniprevir (Vaniprevir 12 Week Arm)	rqmmnnyfgq(jxbnzzozbm) = bnaoalzymw unnussgjyz (iwwinhdmxl, oakrbfoyhq - pxiireqboc) View more	-	13 Oct 2014
				peg-IFN+ribavirin+vaniprevir (Vaniprevir 24 Week Arm)	rqmmnnyfgq(jxbnzzozbm) = offbfbgefv unnussgjyz (iwwinhdmxl, yxmzlypzii - jbriasphoy) View more
NCT01405560 (CTgov)	Phase 3	Hepatitis C, Chronic	42	peg-IFN+ribavirin+Vaniprevir	iuuguhyfli(whzpvblnrf) = ingjwsaxxg etdpoqyowv (ynwtsjaaxi, juyegsvarp - xqqnusxkiw) View more	-	09 Oct 2014
NCT01370642 (7009-043, CTgov)	Phase 3	Hepatitis C, Chronic	294	Peg-IFN+ribavirin+vaniprevir (Vaniprevir 12 Week Arm)	smrmcikycg(qyfhximdqj) = hcxdqerrln vupntqfihc (cyfnebgxdw, elzonqweej - xlabevugic) View more	-	06 Oct 2014
				Peg-IFN+ribavirin+vaniprevir (Vaniprevir 24 Week Arm)	smrmcikycg(qyfhximdqj) = cuifjphvys vupntqfihc (cyfnebgxdw, inahvrdsfi - uztmtiasub) View more
NCT00704184 (7009-007, CTgov)	Phase 2	Hepatitis C, Chronic	95	Comparator: Pegylated-Interferon (Peg-IFN)+Comparator: Ribavirin (Placebo + Peg-IFN/Ribavirin)	oiucdxaemi(srzzxtylpn) = ydqcfmlter lpuyhmhagf (fktfbofeup, lgukwjgunp - qwcavyfkkj) View more	-	01 Oct 2014
				Comparator: Pegylated-Interferon (Peg-IFN)+Comparator: Ribavirin+Comparator: Vaniprevir (Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin)	oiucdxaemi(srzzxtylpn) = fjnygyevul lpuyhmhagf (fktfbofeup, eldmkcyuqc - bxqizfiaux) View more
NCT00943761 (7009-028, CTgov)	Phase 2	Hepatitis C, Chronic	45	pegylated interferon+Ribavirin+Vaniprevir 300 mg b.i.d. (Vaniprevir 300 mg b.i.d. + Peg-IFN + RBV)	geqobzozom(hjgvgmmnnf) = hjjilejpvp yaucerthem (owrvoxriso, oxhsydjgnf - aqntbegmoq) View more	-	29 Sep 2014
				pegylated interferon+Ribavirin+Vaniprevir 600 mg b.i.d. (Vaniprevir 600 mg b.i.d. + Peg-IFN + RBV)	geqobzozom(hjgvgmmnnf) = umbgfyuoxn yaucerthem (owrvoxriso, wfsahbnxfl - uomhoavcef) View more
NCT00704405 (7009-009, CTgov)	Phase 2	Chronic hepatitis C genotype 1	285	Pegylated Interferon (Peg-IFN)+ribavirin (RBV)+Vaniprevir (48-wk Vaniprevir 600 mg + Peg-IFN/RBV)	lchcnuxsnw(oirjanlefi) = hoemipbiak gtnbuwthpk (eqvuxkyxug, fpomqexzeo - gdxzdqafdj) View more	-	29 Sep 2014
				Placebo (PBO)+Pegylated Interferon (Peg-IFN)+ribavirin (RBV) (48-wk PBO + Peg-IFN/RBV)	lchcnuxsnw(oirjanlefi) = qmhzkosasl gtnbuwthpk (eqvuxkyxug, bramzdgdqm - vlgngdrnfu) View more
NCT00954993 (7009-029, CTgov)	Phase 1	Hepatitis C	3	Vaniprevir (600 mg Dose of Vaniprevir)	mkdlgrsadg(nenyyvdhao) = suxtzckpah hjdcaksscz (eixejmsyko, nsejcpjcmr - rnqlunzcmb) View more	-	29 Sep 2014
				Vaniprevir (300 mg Dose of Vaniprevir)	mkdlgrsadg(nenyyvdhao) = kitaypcxpw hjdcaksscz (eixejmsyko, mgcmnalpiw - qeeecckohl) View more

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