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| 2. |
- Ahrén, Bo
(författare)
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Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes.
- 2009
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Ingår i: Nature Reviews. Drug Discovery. - : Springer Science and Business Media LLC. - 1474-1776 .- 1474-1784. ; 8:5, s. 369-385
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Forskningsöversikt (refereegranskat)abstract
- Islet dysfunction - characterized by a combination of defective insulin secretion, inappropriately high glucagon secretion and reduced beta-cell mass - has a central role in the pathophysiology of type 2 diabetes. Several G protein-coupled receptors (GPCRs) expressed in islet beta-cells are known to be involved in the regulation of islet function, and therefore are potential therapeutic targets. This is evident from the recent success of glucagon-like peptide 1 (GLP1) mimetics and dipeptidyl peptidase 4 (DPP4) inhibitors, which promote activation of the GLP1 receptor to stimulate insulin secretion and inhibit glucagon secretion, and also have the potential to increase beta-cell mass. Other islet beta-cell GPCRs that are involved in the regulation of islet function include the glucose-dependent insulinotropic peptide (GIP) receptor, lipid GPCRs, pleiotropic peptide GPCRs and islet biogenic amine GPCRs. This Review summarizes islet GPCR expression, signalling and function, and highlights their potential as targets for the treatment of type 2 diabetes.
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| 3. |
- Eriksson, Bengt I., 1946, et al.
(författare)
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Dabigatran etexilate
- 2008
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Ingår i: Nature Reviews Drug Discovery. - : Springer Science and Business Media LLC. - 1474-1784 .- 1474-1776. ; 7:7, s. 557-8
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Tidskriftsartikel (refereegranskat)
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| 4. |
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| 5. |
- Lagerström, Malin C., et al.
(författare)
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Structural diversity of G protein-coupled receptors and significance for drug discovery
- 2008
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Ingår i: Nature reviews. Drug discovery. - : Springer Science and Business Media LLC. - 1474-1776 .- 1474-1784. ; 7:4, s. 339-357
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Forskningsöversikt (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) are the largest family of membrane-bound receptors and also the targets of many drugs. Understanding of the functional significance of the wide structural diversity of GPCRs has been aided considerably in recent years by the sequencing of the human genome and by structural studies, and has important implications for the future therapeutic potential of targeting this receptor family. This article aims to provide a comprehensive overview of the five main human GPCR families--Rhodopsin, Secretin, Adhesion, Glutamate and Frizzled/Taste2--with a focus on gene repertoire, general ligand preference, common and unique structural features, and the potential for future drug discovery.
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| 8. |
- Michino, Mayako, et al.
(författare)
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Community-wide assessment of GPCR structure modelling and ligand docking : GPCR Dock 2008.
- 2009
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Ingår i: Nature reviews. Drug discovery. - : Springer Science and Business Media LLC. - 1474-1784 .- 1474-1776. ; 8:6, s. 455-63
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Tidskriftsartikel (refereegranskat)abstract
- Recent breakthroughs in the determination of the crystal structures of G protein-coupled receptors (GPCRs) have provided new opportunities for structure-based drug design strategies targeting this protein family. With the aim of evaluating the current status of GPCR structure prediction and ligand docking, a community-wide, blind prediction assessment - GPCR Dock 2008 - was conducted in coordination with the publication of the crystal structure of the human adenosine A(2A) receptor bound to the ligand ZM241385. Twenty-nine groups submitted 206 structural models before the release of the experimental structure, which were evaluated for the accuracy of the ligand binding mode and the overall receptor model compared with the crystal structure. This analysis highlights important aspects for success and future development, such as accurate modelling of structurally divergent regions and use of additional biochemical insight such as disulphide bridges in the extracellular loops.
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| 9. |
- Wikberg, Jarl E. S., et al.
(författare)
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Targeting melanocortin receptors : an approach to treat weight disorders and sexual dysfunction
- 2008
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Ingår i: Nature reviews. Drug discovery. - : Springer Science and Business Media LLC. - 1474-1776 .- 1474-1784. ; 7:4, s. 307-323
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Forskningsöversikt (refereegranskat)abstract
- The melanocortin system has multifaceted roles in the control of body weight homeostasis, sexual behaviour and autonomic functions, and so targeting this pathway has immense promise for drug discovery across multiple therapeutic areas. In this Review, we first outline the physiological roles of the melanocortin system, then discuss the potential of targeting melanocortin receptors by using MC3 and MC4 agonists for treating weight disorders and sexual dysfunction, and MC4 antagonists to treat anorectic and cachectic conditions. Given the complexity of the melanocortin system, we also highlight the challenges and opportunities for future drug discovery in this area.
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