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 of diabetes during acute or chronic exposure and in human type 2 diabetes during short-term exposure. However, several clinical trials of GKAs were discontinued because of declining efficacy during chronic exposure or other issues. In some cases, declining efficacy was associated with an increase in plasma triglycerides. Accordingly, increased hepatic triglyceride production or steatosis was inferred as the likely cause for declining efficacy. However, other mechanisms of tachyphylaxis need to be considered. For example, elevated glucose concentration causes induction of glucose 6-phosphatase (G6pc) and repression of Gck in hepatocytes. This is best explained as an adaptative mechanism to maintain intracellular phosphometabolite homeostasis. Enhancement of G6pc induction and Gck repression by GKAs because of perturbed phosphometabolite homeostasis could explain the decline in GKA efficacy during chronic exposure. Progress in understanding the mechanisms of intracellular phosphometabolite homeostasis is crucial for development of better drug therapies and appropriate dietary intervention for type 2 diabetes.
journal_name
Expert Opin Ther Patjournal_title
Expert opinion on therapeutic patentsauthors
Agius Ldoi
10.1517/13543776.2014.965680subject
Has Abstractpub_date
2014-11-01 00:00:00pages
1155-9issue
11eissn
1354-3776issn
1744-7674journal_volume
24pub_type
杂志文章,评审abstract:INTRODUCTION:The potential therapeutic applications of thyrotropin-releasing hormone (TRH) have attracted attention, based on its broad-spectrum neuropharmacological action rather than its endocrine properties. These central nervous system (CNS)-mediated effects provide the rationale for use of TRH and its analogs in t...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2011.623127
更新日期:2011-11-01 00:00:00
abstract::The application is in the field of adult neurogenesis and its therapeutic potential. It aims to characterize the activity of apigenin and related compounds on adult neurogenesis in vivo and in vitro. Apigenin and related compounds are derivatives used in food products. They were administered intraperitoneally and oral...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543770902721279
更新日期:2009-04-01 00:00:00
abstract::In recent years, the involvement of the Hedgehog (Hh) signaling pathway in various human diseases and dysfunctions has been clearly demonstrated. Smoothened (Smo), one of the upstream signal transducers, has been the most druggable target of the Hh pathway. However, the emergence of resistance to Smo inhibitors and th...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.2016.1132309
更新日期:2016-01-01 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:INTRODUCTION:Around 3% of the world population is infected with HCV, with 3 - 4 million newly infected subjects added to this reservoir every year. At least 10% of these people will develop liver cirrhosis or cancer over time, while no approved vaccine against HCV infection is available to date. AREAS COVERED:This pap...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2011.630662
更新日期:2011-12-01 00:00:00
abstract:INTRODUCTION:The benzopyran derivatives present a wide variety of biological activity and behaviour. At the same time the benzopyran derivatives support their use as therapeutic agents for multiple diseases. Their structural characteristics correlated to physicochemical properties seem to define the extent of the biolo...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2017.1338687
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:Caffeic acid (CA) is broadly distributed in several species of the plant kingdom and is widely consumed in human diet. CA and derivatives have been extensively studied in the past years, which unveiled a broad spectrum of biological activities and potential therapeutic applications. As a result, there has ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2014.959492
更新日期:2014-11-01 00:00:00
abstract:INTRODUCTION:Antimicrobial peptides (AMPs) represent the large group of endogenous compounds widely distributed in nature. Due to their broad spectrum of antibiotic activity, as well as anti-inflammatory and immunomodulatory properties, AMPs became a model for the discovery of novel antimicrobial drugs that could answe...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2016.1176149
更新日期:2016-06-01 00:00:00
abstract:INTRODUCTION:Over the past three years numerous patents and patent applications have been published relating to scientific advances in the use of the green tea polyphenol epigallocatechin gallate (EGCG) (the most abundant, and bioactive compound in green tea) and its analogs as anticancer agents. EGCG affects multiple ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2013.743993
更新日期:2013-02-01 00:00:00
abstract:INTRODUCTION:Benzoxaborole is a versatile boron-heterocyclic scaffold which has found in the last 10 years a broad spectrum of applications in medicinal chemistry, due to its physicochemical and drug-like properties. Use of benzoxaborole moiety in the design of compounds led to the discovery of new classes of anti-bact...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2018.1473379
更新日期:2018-06-01 00:00:00
abstract:INTRODUCTION:HIV/AIDS is one of the most devastating diseases in the world affecting > 40 million people worldwide. Morbidity and mortality from AIDS are significantly reduced due to the advent of highly active antiretroviral therapy (HAART). Long-term toxicity, emergence of drug resistant HIV strains and drug-drug int...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2011.542412
更新日期:2011-02-01 00:00:00
abstract::The interaction between p53 and murine double minute 2 (MDM2) provides an attractive drug target in oncology. Small molecule inhibitors of this interaction have not only provided strong evidence for blocking the protein-protein interaction, but are also extremely useful as biological probes and ultimately as novel the...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.16.2.165
更新日期:2006-02-01 00:00:00
abstract::Diabetes mellitus is a major threat to global public health that requires long-term medical attention. In view of the potentially devastating effects of diabetes on ocular health, it highlights the urgent need of therapeutic drugs for the prevention and treatment of the diabetic complications. The patent described in ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.2016.1163339
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:Many polycationic cell penetrating peptides (CPPs), alternatively named protein transduction domains, have been used for the efficient intracellular delivery of biologically active agents. Patent WO2008/082885 relates to the properties and proposed biomedical applications of a CPP and putative-related sequen...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/17530050902824829
更新日期:2009-09-01 00:00:00
abstract:INTRODUCTION:There has been research on anticancer strategies which focus on disrupting a single malignant protein. One of the strategies is the inhibition of one protein, heat shock protein 90 (Hsp90). There are many reasons why Hsp90 protein is targeted by anticancer agents: maintenance of cellular homeostasis in org...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2013.780597
更新日期:2013-08-01 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::This application claims salts and crystalline forms of a previously disclosed DP2 receptor antagonist (2-[3-[2-(tert-butylsulfanylmethyl)-4-(2,2-dimethylpropanoylamino)phenoxy]-4-methoxy-phenyl]acetic acid (1)). It also claims compositions containing the free acid and its salts, especially the sodium salt and their us...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2011.636738
更新日期:2011-12-01 00:00:00
abstract::The patent claims peptidic/nonpeptidic inhibitors of the ghrelin receptor, the growth hormone secretagogue receptor (GHSR) 1A. Among these compounds, it was disclosed that the addition in some compounds of a GlyMetAla tripeptide at the N-terminus of the ghrelin peptide agonists converts them into ghrelin receptor anta...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.2012.684946
更新日期:2012-06-01 00:00:00
abstract::Introduction: Pharmacotherapy is limited by the inefficient drug targeting of non-healthy cells/tissues. In this pharmacological landscape, liposomes are contributing to the impulse given by Nanotechnology to optimize drug therapy. Areas covered: The analysis of the state-of-the-art in liposomal formulations for drug ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2019.1679767
更新日期:2019-11-01 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 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:Since exendin-4 (exenatide) was approved for diabetes therapy in 2005, several exendin analogs have been developed for the treatment of type 2 diabetes mellitus. As exenatide is a relatively short-acting injectable agent, major approaches have focused on developing long-acting exendin analogs to improve pa...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1080/13543776.2016.1192130
更新日期:2016-07-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:c-Met kinase is the receptor for hepatocyte growth factor. Primarily expressed on epithelial and mesenchymal cells its normal function is associated with wound healing, liver regeneration and embryo development. However, dysregulation of c-Met through overexpression, gene amplification, mutation...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543770903514137
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:Inhibitors of the renin angiotensin aldosterone system (RAAS) represent some of the most widely prescribed, successful and well-tolerated therapeutics of recent times and are of proven worth in the management/prevention of cardiovascular disease and diabetic nephropathy. However, as knowledge has grown about...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543770903008536
更新日期:2009-06-01 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: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::Small-molecule ligands, amenable to positron emission tomography (PET) imaging of different types of neurodegenerative disease-associated amyloid deposits in the CNS of living patients, hold considerable promise for diagnostic purposes, as well as for monitoring disease progression and the effectiveness of treatments....
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.2014.871526
更新日期:2014-03-01 00:00:00
abstract::The two patent applications describe two novel compounds in the benzimidazole class of GyrB/ParE antibacterial agents and multiple phosphate prodrugs derived from these compounds. The new benzimidazole compounds have excellent antibacterial activity on Gram-positive strains. But like previous benzimidazoles, they have...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章
doi:10.1517/13543776.2013.820707
更新日期:2013-09-01 00:00:00
abstract:IMPORTANCE TO THE FIELD:Leukotrienes (LTs) are pivotal lipid mediators of inflammation and allergy and results from recent studies also suggest roles of LTs in cardiovascular diseases, cancer and osteoporosis. 5-Lipoxygenase (5-LO) catalyzes the first step in the biosynthesis of LTs from arachidonic acid, and based on ...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543771003602012
更新日期:2010-03-01 00:00:00
abstract:INTRODUCTION:Dendrimers were widely used in cancer diagnosis and therapy during the past decade. The surface functionalities allow bioactive molecules such as imaging probes, therapeutic compounds, targeting ligands to be present on dendrimer surface in a multivalent fashion. In addition, the interior pockets as well a...
journal_title:Expert opinion on therapeutic patents
pub_type: 杂志文章,评审
doi:10.1517/13543776.2013.761207
更新日期:2013-04-01 00:00:00