Abstract:
BACKGROUND:Diabetes is a chronic disease that occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. Hyperglycemia, or raised blood sugar, is a common effect of uncontrolled diabetes and over time leads to serious damage to many of the body's systems, especially nerves and blood vessels. Diabetes causes about 5% of all deaths globally each year and is likely to increase by > 50% in the next 10 years without urgent action. In light of these alarming statistics, the pharmaceutical industry has been on a quest to characterize more promising molecular targets to satisfy stringent new criteria for anti-hyperglycemic agents introduced by the American Diabetes Association. On to this stage, G-protein-coupled receptor 119 (GPR119) has emerged as arguably one of the most exciting targets for the treatment of type 2 diabetes mellitus in the new millennium. OBJECTIVE:In this review, we outline the current clinical trial landscape and paint a detailed illustration of the key structural information realized from GPR119 agonist campaigns that have recently emerged in the Patent Cooperation Treaty literature. CONCLUSION:GPR119 agonists mediate a unique nutrient-dependent dual elevation of both insulin and glucagon like peptide 1/glucose-dependent insulinotropic peptide levels in vivo. As a stand-alone therapy or in tandem with approved DPP-IV inhibitors, they could herald a brand new treatment paradigm for type 2 diabetes mellitus. With the passage of the first GPR119 agonist clinical candidates into Phase I trials (Arena/Ortho McNeil APD597; Metabolex MBX-2982; Prosidion/OSI PSN821) and confirmatory reports of clinical proof of concept with respect to glycemic control and incretin release, the spotlight has been set for this new class of therapeutic.
journal_name
Expert Opin Ther Patjournal_title
Expert opinion on therapeutic patentsauthors
Jones RM,Leonard JN,Buzard DJ,Lehmann Jdoi
10.1517/13543770903153878subject
Has Abstractpub_date
2009-10-01 00:00:00pages
1339-59issue
10eissn
1354-3776issn
1744-7674journal_volume
19pub_type
杂志文章,评审abstract:INTRODUCTION:Indazoles are heterocyclic moieties rarely found in nature. They are nitrogen containing chemical compounds composed of a pyrazole ring condensed with a benzene ring. Various indazole derivatives have been described with a wide variety of biological activities. This has aroused great interest in the develo...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2018.1472240
更新日期:2018-06-01 00:00:00
abstract:INTRODUCTION:Apoptosis is an important and extensively studied pathway of programmed cell death, which is central to different physiological processes. Varied pathological implications, not limited to cancer and neurodegenerative diseases, occur if a slight dysfunction happens in the intricate apoptotic pathway. Theref...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2014.877445
更新日期:2014-03-01 00:00:00
abstract:INTRODUCTION:Xanthine oxidase (XO) is a molybdoflavoprotein that catalyzes the oxidative hydroxylation of purines to produce uric acid and reactive oxygen species. These reaction products can cause severe disease conditions like hyperuricemia which makes XO enzyme, an important therapeutic target in diseases like gout....
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1080/13543776.2020.1811233
更新日期:2020-10-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Aberrant activation of signal transducer and activator of transcription (Stat) 3, a member of the STAT family of proteins, is prevalent in numerous human cancers and is now widely recognized as a critical molecular abnormality and a master regulator of tumor processes. Thus, the identification o...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2011.539205
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:The bacterial topoisomerases DNA gyrase and topoisomerase IV are validated targets for development of novel antibacterial agents. Fluoroquinolones inhibit the catalytic GyrA and/or ParC(GrlA) subunit and have been commonly used, although these have toxicity liabilities that restrict their use. The ATPase G...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2019.1575362
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND:Hydrogen sulfide (H(2)S) and carbon monoxide (CO) are endogenously produced gaseous autacoids that regulate a number of physiological processes, including the inflammatory response, cell death and proliferation, neural transmission and smooth muscle tone. OBJECTIVE/METHODS:The current review aims to provide...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543770902858824
更新日期:2009-05-01 00:00:00
abstract:INTRODUCTION:Na/K-ATPase is a heterodimeric transmembrane protein that regulates neuronal signaling, ion homeostasis, muscle contraction and substrate transportation. Modulators of Na/K-ATPase inhibit Na(+)/K(+) exchange and increase cytosolic Ca(2+) to induce inotropic activity in heart failure patients. Besides produ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2012.690033
更新日期:2012-06-01 00:00:00
abstract:INTRODUCTION:Therapeutic antibodies have grown to become an important product class within the biopharmaceutical market. A prerequisite to their commercialization is adequate patent protection. Disclosure requirements and the types of claims available in different jurisdictions can impact the scope of protection availa...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2017.1296950
更新日期:2017-08-01 00:00:00
abstract::Cholesterol homeostasis maintenance is regulated by a cellular feedback system that senses cholesterol amount in cellular membranes. 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMGR) plays a pivotal role in cholesterol metabolism as it is the key rate-limiting enzyme of its biosynthetic pathway; its inhibition pr...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.2015.1061996
更新日期:2015-01-01 00:00:00
abstract::The concept of activation of glucokinase (encoded by the Gck gene) as a potential therapy for type 2 diabetes has been explored by several pharmaceutical companies. Small-molecule Gck activators (GKAs) were found to be effective at increasing glucose disposal by hepatocytes and lowering blood glucose in animal models ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2014.965680
更新日期:2014-11-01 00:00:00
abstract:BACKGROUND:The family of G-protein-coupled receptors (GPCRs) serves as the target for almost a third of currently marketed drugs and provides the predominant mechanism through which extracellular factors transmit signals to the cell. GPCRs have been proved to be good therapeutic targets for metabolic disorders. In rece...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543770802665717
更新日期:2009-02-01 00:00:00
abstract:INTRODUCTION:The use of inhibitors of HIV-1 integrase for treating HIV-1 infection has proven to be very beneficial. Raltegravir, a strand transfer inhibitor, has been approved for use both as a first-line therapy and in treatment-experienced patients. A second compound in this class, elvitegravir, is in Phase III clin...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2011.586631
更新日期:2011-08-01 00:00:00
abstract:INTRODUCTION:Today, over 20 million people suffer from Alzheimer's disease (AD) worldwide. AD has become a critical issue to human health, especially in aging societies, and therefore it is a research hotspot in the global scientific community. The technology flow method differs from traditional reviews generating an i...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2018.1439475
更新日期:2018-04-01 00:00:00
abstract::In the upcoming case of Teva Pharmaceuticals v. Sandoz, the U.S. Supreme Court will address how much deference the appellate court should afford to a trial court's claim construction ruling. The effect of this decision will be far-reaching, as how claims are construed can determine whether a patent is infringed or not...
journal_title:Expert opinion on therapeutic patents
pub_type: 社论
doi:10.1517/13543776.2014.977866
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Amino acid depletion in the blood serum is currently being exploited and explored for therapies in tumors or viral infections that are auxotrophic for a certain amino acid or have a metabolic defect and cannot produce it. The success of these treatments is because normal cells remain unaltered since they a...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2017.1254194
更新日期:2017-03-01 00:00:00
abstract::Increasing pharmacological studies have demonstrated that organic cation transporter 3 (OCT3) plays an important role in controlling the extracellular concentrations of released monoamine neurotransmitter, suggesting that OCT3 might be a promising target in the treatment of depression. As a consequence, compounds show...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1080/13543776.2016.1180364
更新日期:2016-08-01 00:00:00
abstract:INTRODUCTION:The oxadiazoles represent a class of five-membered heterocyclic compounds which are of considerable interest in different areas of medicinal chemistry and drug discovery. Oxadiazoles can exist in different regioisomeric forms and employ in various agents with a broad range of biological activities. This re...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2013.797409
更新日期:2013-09-01 00:00:00
abstract:INTRODUCTION:New drug formulations against hypertension have a vital role in the quality of human life, as this risk factor for cardiovascular disease can be life threatening. A modern life style characterized by less exercise, smoking, drinking and poor diet has increased the risk of developing hypertension, the so-ca...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2015.1086337
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:The N-acylhydrazone (NAH) moiety has been characterized as a privileged structure, capable of providing ligands points for more than one type of bioreceptor. Modifications of the subunits bonded to its acyl and imine functions resulted in several derivatives, which modulate a great diversity of molecular t...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2014.959491
更新日期:2014-11-01 00:00:00
abstract:INTRODUCTION:New classes of synthetic and semi-synthetic β-glucan inhibitors have recently emerged, providing analogs that, in some cases, have been proven to have a high degree of activity against fungi, offering the prospect of alternatives to the commercially available lipopeptide/echinocandin agents caspofungin, mi...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2011.603899
更新日期:2011-10-01 00:00:00
abstract::A small series of aryl(1-arylamino)ethyl,1,5-naphthyridine derivatives that selectively inhibit PI3Kδ was prepared. The compounds are claimed to be useful in the treatment of cancer, inflammatory and autoimmune diseases. The compounds represent further variations around a structural motif explored in a number of previ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.2011.622749
更新日期:2011-11-01 00:00:00
abstract:INTRODUCTION:TANK-binding kinase 1 (TBK1) is a noncanonical IκB kinase family member that regulates the innate immune response. Misregulation of TBK1 activity can promote inflammatory disorders and oncogenesis; therefore, TBK1 inhibitors are considered a promising therapy for inflammation and cancer. AREAS COVERED:In ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2015.1081168
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Nuclear factor (NF)-κB, as transcription factor, is linked to the expression of various genes and plays an essential role in immune and inflammatory responses. Abnormal NF-κB signaling results in human diseases, such as immune disorders, inflammation and various cancers. Therefore, regulation of NF-κB may ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2011.638285
更新日期:2011-12-01 00:00:00
abstract:INTRODUCTION:Tropomyosin receptor kinases (TrkA/B/C) play crucial roles in the development and maintenance of the nervous system, and aberrant expression of Trk has been implicated in neurological disorders as well as neural and non-neural neoplasms. Patent activity encompassing Trk inhibitors has grown substantially o...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2017.1297796
更新日期:2017-06-01 00:00:00
abstract::Muscular dystrophies (MD) are commonly characterized by progressive loss of muscle mass and function. It is hypothesized that therapeutic blockade of the TGF-β ligand myostatin, a negative regulator of muscle mass, will stimulate muscle growth and restore muscle function. Although many anti-myostatin targets are curre...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.2015.1007954
更新日期:2015-05-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Following FDA approval of vorinostat in 2006, several novel HDAC inhibitors (HDACis) have entered clinical trials, and there are numerous published patent applications claiming novel HDACis which were optimized as potential drug candidates, designed for regional or systemic release, and created ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543770903393789
更新日期:2009-12-01 00:00:00
abstract:INTRODUCTION:Monoacylglycerol lipase (MAGL) belongs to the endocannabinoid system and is responsible for the inactivation of endocannabinoid 2-arachidonoylglycerol. Importantly, it was found that MAGL degradation of lipids in cancer cells enhances the availability of free fatty acids for new cellular membrane formation...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1080/13543776.2021.1841166
更新日期:2020-11-01 00:00:00
abstract:INTRODUCTION:Due to the role of bradykinin B1 receptor (B1R) in pain and inflammation, B1R antagonists have been suggested as promising drug candidates in chronic pain states. The first disclosed B1R antagonists were peptidomimetics, however, during the last few years, novel chemotypes with improved pharmacodynamic and...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2012.730521
更新日期:2012-12-01 00:00:00
abstract:INTRODUCTION:Melanogenesis is the process of producing the melanin pigment, in which a series of chemical and enzymatic pathways are involved. Modulation at any level of this process would become an important approach in the treatment of hyper- or hypopigmentation-related diseases. Since hyperpigmentation covers import...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2015.1039985
更新日期:2015-07-01 00:00:00
abstract::A series of 10 closely related patent applications define Theravance's approach to the development of long-acting M(3) selective antagonists for the treatment of chronic obstructive pulmonary disease. The applications illustrate a modular approach to the design of such agents, comprising a muscarinic pharmacophore att...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.16.9.1321
更新日期:2006-09-01 00:00:00