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News Article | May 15, 2017
Site: en.prnasia.com

SHANGHAI, May 15, 2017 /PRNewswire/ -- WuXi AppTec, a leading global pharmaceutical, biotechnology and medical device open-access capability and technology platform, today announced that it has completed its acquisition of HD Biosciences (HDB), a leading biology focused preclinical drug discovery contract research organization (CRO). Headquartered in Shanghai, HD Biosciences is a leading biology and preclinical service provider. Its plate-based pharmacology & screening capability and AGMTM based target validation are industry leading platforms with great reputation. The company also provides hit identification, lead discovery, in vivo pharmacology and other related services. The acquisition will further strengthen WuXi's R&D capability from target validation to lead discovery and optimization, improving and expanding WuXi's open-access enabling service platform. "My colleagues and I are very excited to be part of WuXi AppTec family," said Dr. Xuehai Tan, Chairman and CEO of HD Biosciences. "The merger will provide additional resources and space to, take our biology focused capabilities to a next level and to speed up the growth of our business into a leading global player within our sector. We will provide better services to our current clients and potentially expand services to WuXi's global customers." Dr. Xuehai Tan will become a Senior Vice President of WuXi AppTec, and the President of HD Biosciences. HD Bioscience will become a wholly owned subsidiary of WuXi AppTec and a member of WuXi's Research Service Division and continue to focus on its core capabilities and business growth. "We are very pleased to have HD Biosciences join the WuXi team," said Dr. Ge Li, Chairman and Chief Executive Officer of WuXi AppTec. "This business combination is an important step in WuXi's development of the most comprehensive capability and technology platform in industry to enable anyone, and any company to discover and develop better medicines and healthcare products for patients, and to realize our vision that 'every drug can be made and every disease can be treated'." WuXi AppTec is a leading global pharmaceutical, biopharmaceutical, and medical device open-access capability and technology platform company with global operations. As an innovation-driven and customer-focused company, WuXi AppTec provides a broad and integrated portfolio of services to help our worldwide customers and partners shorten the discovery and development time and lower the cost of drug and medical device R&D through cost-effective and efficient solutions. With its industry-leading capabilities such as small molecule R&D and manufacturing, cell therapy and gene therapy R&D and manufacturing, and medical device testing, WuXi platform is enabling nearly 3,000 innovative collaborators from more than 30 countries to bring innovative healthcare products to patients, and to fulfill WuXi's dream that "every drug can be made and every disease can be treated."  Please visit http://www.wuxiapptec.com


News Article | May 15, 2017
Site: www.prnewswire.com

"My colleagues and I are very excited to be part of WuXi AppTec family," said Dr. Xuehai Tan, Chairman and CEO of HD Biosciences. "The merger will provide additional resources and space to, take our biology focused capabilities to a next level and to speed up the growth of our business into a leading global player within our sector. We will provide better services to our current clients and potentially expand services to WuXi's global customers." Dr. Xuehai Tan will become a Senior Vice President of WuXi AppTec, and the President of HD Biosciences. HD Bioscience will become a wholly owned subsidiary of WuXi AppTec and a member of WuXi's Research Service Division and continue to focus on its core capabilities and business growth. "We are very pleased to have HD Biosciences join the WuXi team," said Dr. Ge Li, Chairman and Chief Executive Officer of WuXi AppTec. "This business combination is an important step in WuXi's development of the most comprehensive capability and technology platform in industry to enable anyone, and any company to discover and develop better medicines and healthcare products for patients, and to realize our vision that 'every drug can be made and every disease can be treated'." WuXi AppTec is a leading global pharmaceutical, biopharmaceutical, and medical device open-access capability and technology platform company with global operations. As an innovation-driven and customer-focused company, WuXi AppTec provides a broad and integrated portfolio of services to help our worldwide customers and partners shorten the discovery and development time and lower the cost of drug and medical device R&D through cost-effective and efficient solutions. With its industry-leading capabilities such as small molecule R&D and manufacturing, cell therapy and gene therapy R&D and manufacturing, and medical device testing, WuXi platform is enabling nearly 3,000 innovative collaborators from more than 30 countries to bring innovative healthcare products to patients, and to fulfill WuXi's dream that "every drug can be made and every disease can be treated."  Please visit http://www.wuxiapptec.com To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/wuxi-apptec-completes-acquisition-of-hd-biosciences-300457448.html


News Article | May 29, 2017
Site: www.prnewswire.com

NEW YORK, May 29, 2017 /PRNewswire/ -- This report analyzes the worldwide markets for Contract Research Outsourcing in US$ Million by the following Service Segments: Drug Discovery, Preclinical Research, and Clinical Research. The report provides separate comprehensive analytics for the US, Canada, Japan, Europe, Asia-Pacific, and Rest of World. Annual estimates and forecasts are provided for the period 2015 through 2022. Also, a six-year historic analysis is provided for these markets. Read the full report: http://www.reportlinker.com/p04910444/Global-Contract-Research-Outsourcing-Services.html Market data and analytics are derived from primary and secondary research. Company profiles are primarily based on public domain information including company URLs. The report profiles 115 companies including many key and niche players such as - Albany Molecular Research, Inc. - Charles River Laboratories International, Inc. - Chiltern International Ltd. - ICON plc Read the full report: http://www.reportlinker.com/p04910444/Global-Contract-Research-Outsourcing-Services.html I. INTRODUCTION, METHODOLOGY & PRODUCT DEFINITIONS Study Reliability and Reporting Limitations Disclaimers Data Interpretation & Reporting Level Quantitative Techniques & Analytics Product Definitions and Scope of Study II. EXECUTIVE SUMMARY 1. INDUSTRY OVERVIEW Outsourcing of R&D Projects to Propel CROs Services Market Growth Drivers in a Nutshell Evolving Macro Trends Driving CRO Demand CROs to Significantly Drive Outsourcing Penetration Focus on Efficient, Quality Services to Drive Specialty CROs Market Rise in Investments to Boost Growth Key Therapeutic Areas of Clinical Trial Research Table 1: Global Clinical Trial Services Market by Therapeutic Area: 2016 (includes corresponding Graph/Chart) Primary Factors Influencing CRO Market Pharma and Biotech Companies to Increase Dependence on CROs Outlook Notable Regional Developments Future Model of CRO 2. COMPETITIVE SCENARIO CRO - A Highly Fragmented Market Table 2: Leading Players in the Global Contract Research Outsourcing Market (2016E): Percentage Breakdown of Revenues by Player (includes corresponding Graph/Chart) Table 3: Percentage Breakup of Life Sciences Revenues (2016) of Major Players by Service Type- Preclinical, Phase I, Phase IIA, Phase IIB, Phase III, Phase IV/ Post-Approval, Central Lab and Others Large CROs Seek the Inorganic Growth Route Global CRO Marketspace - A Review of the M&A Activity in the Recent Years Select M&A Activity in the Global CRO Market Noteworthy Contracts of Major CROs CROs Adept with New Technologies to See More Business in Future Streamlining Development of Novel Trial Designs CROs with End-to End Capabilities in Demand Key Opportunities for CROs Technological Superiority - A Definite Advantage Strategies and Tactical Programs for CROs Survival Strategies in Mature CRO Markets Exit from the Industry Expand Scale Capture Niche Segments Strategies to Tap Opportunities in Growing Markets Mobilize Funds Expand Other Services Upgrade Technological and Knowledge Base Form Sub-Contracts or Regional Alliances 3. GROWTH DRIVERS, MARKET TRENDS & ISSUES Increased Spend on R&D Outsourcing Table 4: Global Pharmaceutical R&D Spending (US$ Billion) for the Years 2010 through 2017 (includes corresponding Graph/Chart) Table 5: Percentage Breakdown of Total Number of Compounds in Pipeline by Phase for Pre-Clinical, Phase I, Phase II and Phase III: 2016E (includes corresponding Graph/Chart) Enhancing Site Selection and Patient Enrollment CROs Enter into Alliances to Improve Efficiencies Adoption of Digital Technologies Gains Pace Rising Late-Stage Services Demand and Budget Restraints Drive Market Growth Toxicology Services Gain Notable Attention Pharma Companies Enter into Licensing Agreements with Biotech Companies for New Drug Discovery - A Mutually Beneficial Strategy Pharmaceutical & Biopharmaceutical Trends to Support CRO Penetration Table 6: Global Biopharma % R&D Outsourcing (2014-2020) (includes corresponding Graph/Chart) Table 7: New FDA Drug Approvals (2010-2016): Breakdown of Number of Approvals by Type for New Molecular Entity (NME) and Biologic License Application (BLA) Approvals (includes corresponding Graph/Chart) Focus on Regulatory Oversight and Enhanced Transparency Bodes Well for CROs eClinical Solutions Gain Traction Other Noteworthy Market Trends CROs Monetize Data Service Differentiation - A Sustaining Strategy CROs Tie Up with Diagnostic Companies for Patients Research Networks Move to Cloud Application of Mobile Devices to Collect Real Time Data Gains Ground CROs Provide Exclusive Offers to Lure Big Pharma Challenges Faced by Contract Research Organizations On-shore versus Offshore CRO Business Cutthroat Competition among CROs Management of Clinical Investigation Cost Containment Safety Concerns on Clinical Trials Pipeline Blocks Surging Global Population Offers Increased Growth Opportunities Table 8: Top 25 Countries Worldwide in Terms of Population: 2015 & 2016 (In Million) (includes corresponding Graph/Chart) Aging Population Boosts Opportunities for CRO Table 9: Global Population Statistics for the 65+ Age Group (2015) (includes corresponding Graph/Chart) Table 10: Comparison of Aging Population by Country (1980, 2015 & 2050): Percentage Share of Population Aged Above-65 Years of the Overall Population for Select Countries (includes corresponding Graph/Chart) Increasing Healthcare Expenditure to Spur Demand for Generics Table 11: Healthcare Spending as a Percentage of GDP by Region (2016E) (includes corresponding Graph/Chart) 4. CONTRACT RESEARCH OUTSOURCING - AN INSIGHT Concept Contract Research Organizations (CRO) Contract Research Outsourcing Major CRO Services Ancillary CRO Services Advantages from CRO Drug Discovery Pre-Clinical Studies Clinical Research - Factors Encouraging CRO Services at Various Phases Phase I Phase II Phase III Phase IV 5. RECENT INDUSTRY ACTIVITY WuXi AppTec Takes Over HD Biosciences Laboratory Corporation of America Holdings to Acquire Pharmaceutical Product Development PRA Health Sciences and Takeda Pharmaceutical Inks New Partnership AMRI Enters into Alliance with Bruker Daltonics and HighRes Biosolutions Pharmaceutical Product Development Establishes Rare Disease and Pediatric Center of Excellence Pharmaceutical Product Development to Start Clinical Research Unit in Las Vegas Bracket Acquires CLINapps PAREXEL International to Acquire ExecuPharm Cinven to Takeover BioClinica ICON to Takeover Clinical Research Management Pharmaceutical Product Development Acquires Evidera Velocity Fund Partners Acquires Indipharm Bioclinica Snaps Up Compass Research Charles River Laboratories International Takes Over Agilux Laboratories Charles River Laboratories International Snaps Up Blue Stream Laboratories Charles River Laboratories International Acquires WIL Research Pharmaron Announces the Acquisition of Quotient Bioresearch Amulet Capital Partners Acquires SynteractHCR Holdings IMS Health Merges with Quintiles Almac Clinical Technologies Enters into Partnership with inVentiv Health CSSi LifeSciences Unveils Fully Integrated Medical Device CRO Lovelace Biomedical Commences Operations as Preclinical CRO PAREXEL International Inks Services Agreement with Pfizer BioDuro Commences Operations as a Contract Research and Manufacturing Firm Charles River Laboratories International Forms Partnership with BioMotiv Laboratory Corporation of America Acquires Covance Charles River Laboratories International Snaps Up Oncotest Chiltern Acquires Theorem Clinical Research Charles River Laboratories International Takes Over Celsis International Albany Molecular Research Unveils Integrated Drug Discovery Center 6. FOCUS ON SELECT GLOBAL PLAYERS Albany Molecular Research, Inc. (USA) Charles River Laboratories International, Inc. (USA) Chiltern International Ltd. (UK) ICON plc (Ireland) INC Research, LLC (USA) InVentiv Health, Inc. (USA) Jubilant Biosys Ltd. (India) Laboratory Corporation of America® Holdings (USA) PAREXEL International Corp. (USA) Pharmaceutical Product Development, LLC. (USA) Pharmaron (China) PRA Health Sciences, Inc. (USA) Quintiles IMS Holdings, Inc. (USA) Ricerca Biosciences LLC (USA) Sygnature Discovery Limited (UK) SynteractHCR (USA) WuXi AppTec (China) 7. GLOBAL MARKET PERSPECTIVE Table 12: World Recent Past, Current & Future Analysis for Contract Research Outsourcing by Geographic Region - US, Canada, Japan, Europe, Asia-Pacific (excluding Japan) and Rest of World Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2015 through 2022 (includes corresponding Graph/Chart) Table 13: World Historic Review for Contract Research Outsourcing by Geographic Region - US, Canada, Japan, Europe, Asia-Pacific (excluding Japan) and Rest of World Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2009 through 2014 (includes corresponding Graph/Chart) Table 14: World 14-Year Perspective for Contract Research Outsourcing by Geographic Region - Percentage Breakdown of Revenues for US, Canada, Japan, Europe, Asia-Pacific (excluding Japan) and Rest of World Markets for Years 2009, 2017 & 2022 (includes corresponding Graph/Chart) Table 15: World Recent Past, Current & Future Analysis for Contract Research Outsourcing for Drug Discovery by Geographic Region - US, Canada, Japan, Europe, Asia-Pacific (excluding Japan) and Rest of World Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2015 through 2022 (includes corresponding Graph/Chart) Table 16: World Historic Review for Contract Research Outsourcing for Drug Discovery by Geographic Region - US, Canada, Japan, Europe, Asia-Pacific (excluding Japan) and Rest of World Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2009 through 2014 (includes corresponding Graph/Chart) Table 17: World 14-Year Perspective for Contract Research Outsourcing for Drug Discovery by Geographic Region - Percentage Breakdown of Revenues for US, Canada, Japan, Europe, Asia-Pacific (excluding Japan) and Rest of World Markets for Years 2009, 2017 & 2022 (includes corresponding Graph/Chart) Table 18: World Recent Past, Current & Future Analysis for Contract Research Outsourcing for Preclinical Research by Geographic Region - US, Canada, Japan, Europe, Asia-Pacific (excluding Japan) and Rest of World Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2015 through 2022 (includes corresponding Graph/Chart) Table 19: World Historic Review for Contract Research Outsourcing for Preclinical Research by Geographic Region - US, Canada, Japan, Europe, Asia-Pacific (excluding Japan) and Rest of World Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2009 through 2014 (includes corresponding Graph/Chart) Table 20: World 14-Year Perspective for Contract Research Outsourcing for Preclinical Research by Geographic Region - Percentage Breakdown of Revenues for US, Canada, Japan, Europe, Asia-Pacific (excluding Japan) and Rest of World Markets for Years 2009, 2017 & 2022 (includes corresponding Graph/Chart) Table 21: World Recent Past, Current & Future Analysis for Contract Research Outsourcing for Clinical Research by Geographic Region - US, Canada, Japan, Europe, Asia-Pacific (excluding Japan) and Rest of World Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2015 through 2022 (includes corresponding Graph/Chart) Table 22: World Historic Review for Contract Research Outsourcing for Clinical Research by Geographic Region - US, Canada, Japan, Europe, Asia-Pacific (excluding Japan) and Rest of World Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2009 through 2014 (includes corresponding Graph/Chart) Table 23: World 14-Year Perspective for Contract Research Outsourcing for Clinical Research by Geographic Region - Percentage Breakdown of Revenues for US, Canada, Japan, Europe, Asia-Pacific (excluding Japan) and Rest of World Markets for Years 2009, 2017 & 2022 (includes corresponding Graph/Chart) III. MARKET 1. THE UNITED STATES A.Market Analysis Outlook Drug Developers Rely on CROs to Improve Trial Efficiency and Cost Savings Trial Services Witness Higher Demand Strong Demand for Data Management Services Focus on Innovation and Productivity CROs Focus on Adaptive Clinical Trials Risk-based Monitoring Catches Pace Strategic Corporate Developments Key Players B.Market Analytics Table 24: US Recent Past, Current & Future Analysis for Contract Research Outsourcing by Service Type - Drug Discovery, Preclinical Research and Clinical Research Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2015 through 2022 (includes corresponding Graph/Chart) Table 25: US Historic Review for Contract Research Outsourcing by Service Type - Drug Discovery, Preclinical Research and Clinical Research Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2009 through 2014 (includes corresponding Graph/Chart) Table 26: US 14-Year Perspective for Contract Research Outsourcing by Service Type - Percentage Breakdown of Revenues for Drug Discovery, Preclinical Research and Clinical Research Markets for Years 2009, 2017 & 2022 (includes corresponding Graph/Chart) 2. CANADA Market Analysis Table 27: Canadian Recent Past, Current & Future Analysis for Contract Research Outsourcing by Service Type - Drug Discovery, Preclinical Research and Clinical Research Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2015 through 2022 (includes corresponding Graph/Chart) Table 28: Canadian Historic Review for Contract Research Outsourcing by Service Type - Drug Discovery, Preclinical Research and Clinical Research Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2009 through 2014 (includes corresponding Graph/Chart) Table 29: Canadian 14-Year Perspective for Contract Research Outsourcing by Service Type - Percentage Breakdown of Revenues for Drug Discovery, Preclinical Research and Clinical Research Markets for Years 2009, 2017 & 2022 (includes corresponding Graph/Chart) 3. JAPAN A.Market Analysis Strategic Corporate Development B.Market Analytics Table 30: Japanese Recent Past, Current & Future Analysis for Contract Research Outsourcing by Service Type - Drug Discovery, Preclinical Research and Clinical Research Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2015 through 2022 (includes corresponding Graph/Chart) Table 31: Japanese Historic Review for Contract Research Outsourcing by Service Type - Drug Discovery, Preclinical Research and Clinical Research Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2009 through 2014 (includes corresponding Graph/Chart) Table 32: Japanese 14-Year Perspective for Contract Research Outsourcing by Service Type - Percentage Breakdown of Revenues for Drug Discovery, Preclinical Research and Clinical Research Markets for Years 2009, 2017 & 2022 (includes corresponding Graph/Chart) 4. EUROPE A.Market Analysis Outlook Providers Expand Services in Downstream Drug Development Strategic corporate developments Key Players B.Market Analytics Table 33: European Recent Past, Current & Future Analysis for Contract Research Outsourcing by Service Type - Drug Discovery, Preclinical Research and Clinical Research Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2015 through 2022 (includes corresponding Graph/Chart) Table 34: European Historic Review for Contract Research Outsourcing by Service Type - Drug Discovery, Preclinical Research and Clinical Research Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2009 through 2014 (includes corresponding Graph/Chart) Table 35: European 14-Year Perspective for Contract Research Outsourcing by Service Type - Percentage Breakdown of Revenues for Drug Discovery, Preclinical Research and Clinical Research Markets for Years 2009, 2017 & 2022 (includes corresponding Graph/Chart) 5. ASIA-PACIFIC A.Market Analysis Outlook Asia-Pacific to Push up Volume Share in CRO Market R&D Outsourcing in Life Sciences on Rise Focus on Select Regional Markets China Market with Strong Growth Potential India Australia Popular Destination for Early Phase Clinical Trials Cost Savings through Tax Incentives Supportive Regulatory Framework Government Focus on Reducing Cost and Time Superior Clinical Trial Quality Strategic Corporate Development Key Players B.Market Analytics Table 36: Asia-Pacific Recent Past, Current & Future Analysis for Contract Research Outsourcing by Geographic Region - China, India and Rest of Asia-Pacific Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2015 through 2022 (includes corresponding Graph/Chart) Table 37: Asia-Pacific Historic Review for Contract Research Outsourcing by Geographic Region - China, India and Rest of Asia-Pacific Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2009 through 2014 (includes corresponding Graph/Chart) Table 38: Asia-Pacific 14-Year Perspective for Contract Research Outsourcing by Geographic Region - Percentage Breakdown of Revenues for China, India and Rest of Asia-Pacific Markets for Years 2009, 2017 & 2022 (includes corresponding Graph/Chart) Table 39: Asia-Pacific Recent Past, Current & Future Analysis for Contract Research Outsourcing by Service Type - Drug Discovery, Preclinical Research and Clinical Research Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2015 through 2022 (includes corresponding Graph/Chart) Table 40: Asia-Pacific Historic Review for Contract Research Outsourcing by Service Type - Drug Discovery, Preclinical Research and Clinical Research Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2009 through 2014 (includes corresponding Graph/Chart) Table 41: Asia-Pacific 14-Year Perspective for Contract Research Outsourcing by Service Type - Percentage Breakdown of Revenues for Drug Discovery, Preclinical Research and Clinical Research Markets for Years 2009, 2017 & 2022 (includes corresponding Graph/Chart) 6. REST OF WORLD A.Market Analysis Outlook Providers with Specialized Research Techniques to Boost Latin American CRO Market B.Market Analytics Table 42: Rest of World Recent Past, Current & Future Analysis for Contract Research Outsourcing by Service Type - Drug Discovery, Preclinical Research and Clinical Research Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2015 through 2022 (includes corresponding Graph/Chart) Table 43: Rest of World Historic Review for Contract Research Outsourcing by Service Type - Drug Discovery, Preclinical Research and Clinical Research Markets Independently Analyzed with Annual Revenue Figures in US$ Million for Years 2009 through 2014 (includes corresponding Graph/Chart) Table 44: Rest of World 14-Year Perspective for Contract Research Outsourcing by Service Type - Percentage Breakdown of Revenues for Drug Discovery, Preclinical Research and Clinical Research Markets for Years 2009, 2017 & 2022 (includes corresponding Graph/Chart) IV. COMPETITIVE LANDSCAPE Total Companies Profiled: 115 (including Divisions/Subsidiaries - 120) The United States (47) Canada (5) Japan (1) Europe (27) - France (2) - Germany (6) - The United Kingdom (3) - Spain (1) - Rest of Europe (15) Asia-Pacific (Excluding Japan) (35) Latin America (4) Read the full report: http://www.reportlinker.com/p04910444/Global-Contract-Research-Outsourcing-Services.html About Reportlinker ReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place. http://www.reportlinker.com __________________________ Contact Clare: clare@reportlinker.com US: (339)-368-6001 Intl: +1 339-368-6001 To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/global-contract-research-outsourcing---services-300465052.html


Camara A.K.S.,Medical College of Wisconsin | Zhou Y.,HD Biosciences | Wen P.-C.,University of Illinois at Urbana - Champaign | Tajkhorshid E.,University of Illinois at Urbana - Champaign | Kwok W.-M.,Medical College of Wisconsin
Frontiers in Physiology | Year: 2017

Mitochondria are the key source of ATP that fuels cellular functions, and they are also central in cellular signaling, cell division and apoptosis. Dysfunction of mitochondria has been implicated in a wide range of diseases, including neurodegenerative and cardiac diseases, and various types of cancer. One of the key proteins that regulate mitochondrial function is the voltage-dependent anion channel 1 (VDAC1), the most abundant protein on the outer membrane of mitochondria. VDAC1 is the gatekeeper for the passages of metabolites, nucleotides, and ions; it plays a crucial role in regulating apoptosis due to its interaction with apoptotic and anti-apoptotic proteins, namely members of the Bcl-2 family of proteins and hexokinase. Therefore, regulation of VDAC1 is crucial not only for metabolic functions of mitochondria, but also for cell survival. In fact, multiple lines of evidence have confirmed the involvement of VDAC1 in several diseases. Consequently, modulation or dysregulation of VDAC1 function can potentially attenuate or exacerbate pathophysiological conditions. Understanding the role of VDAC1 in health and disease could lead to selective protection of cells in different tissues and diverse diseases. The purpose of this review is to discuss the role of VDAC1 in the pathogenesis of diseases and as a potentially effective target for therapeutic management of various pathologies. © 2017 Camara, Zhou, Wen, Tajkhorshid and Kwok.


Tewari S.G.,University of Michigan | Zhou Y.,HD Biosciences | Otto B.J.,Medical College of Wisconsin | Dash R.K.,Medical College of Wisconsin | And 2 more authors.
Frontiers in Physiology | Year: 2015

The voltage-dependent anion channel (VDAC) is the main conduit for permeation of solutes (including nucleotides and metabolites) of up to 5 kDa across the mitochondrial outer membrane (MOM). Recent studies suggest that VDAC activity is regulated via post-translational modifications (PTMs). Yet the nature and effect of these modifications is not understood. Herein, single channel currents of wild-type, nitrosated, and phosphorylated VDAC are analyzed using a generalized continuous-time Markov chain Monte Carlo (MCMC) method. This developed method describes three distinct conducting states (open, half-open, and closed) of VDAC activity. Lipid bilayer experiments are also performed to record single VDAC activity under un-phosphorylated and phosphorylated conditions, and are analyzed using the developed stochastic search method. Experimental data show significant alteration in VDAC gating kinetics and conductance as a result of PTMs. The effect of PTMs on VDAC kinetics is captured in the parameters associated with the identified Markov model. Stationary distributions of the Markov model suggest that nitrosation of VDAC not only decreased its conductance but also significantly locked VDAC in a closed state. On the other hand, stationary distributions of the model associated with un-phosphorylated and phosphorylated VDAC suggest a reversal in channel conformation from relatively closed state to an open state. Model analyses of the nitrosated data suggest that faster reaction of nitric oxide with Cys-127 thiol group might be responsible for the biphasic effect of nitric oxide on basal VDAC conductance. © 2015 Tewari, Zhou, Otto, Dash, Kwok and Beard.


Pietra C.,Helsinn Healthcare SA | Takeda Y.,ONO Pharmaceutical Co. | Tazawa-Ogata N.,ONO Pharmaceutical Co. | Minami M.,ONO Pharmaceutical Co. | And 3 more authors.
Journal of Cachexia, Sarcopenia and Muscle | Year: 2014

Background: Anamorelin HCl (ANAM) is a novel, orally active, ghrelin receptor agonist in clinical development for the treatment of cancer cachexia. We report in vitro and in vivo studies evaluating the preclinical pharmacologic profile of ANAM.Results: ANAM showed significant agonist and binding activity on the ghrelin receptor, and stimulated GH release in vitro. In rats, ANAM significantly and dose-dependently increased FI and BW at all dose levels compared with control, and significantly increased GH levels at 10 or 30 mg/kg doses. Increases in GH and IGF-1 levels were observed following ANAM administration in pigs.Conclusion: ANAM is a potent and highly specific ghrelin receptor agonist with significant appetite-enhancing activity, leading to increases in FI and BW, and a stimulatory effect on GH secretion. These results support the continued investigation of ANAM as a potential treatment of cancer anorexia-cachexia syndrome.Methods: Fluorescent imaging plate reader and binding assays in HEK293 and baby hamster kidney cells determined the agonist and antagonist activity of ANAM, and its affinity for the ghrelin receptor. Rat pituitary cells were incubated with ANAM to evaluate its effect on growth hormone (GH) release. In vivo, rats were treated with ANAM 3, 10, or 30 mg/kg, or control orally, once daily for 6 days to evaluate the effect on food intake (FI) and body weight (BW), and once to assess GH response. In pigs, single (3.5 mg/kg) or continuous (1 mg/kg/day) ANAM doses were administered to assess GH and insulin-like growth factor (IGF-1) response. © 2014, Springer-Verlag Berlin Heidelberg.

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