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| Richardnede | Дата: Суббота, 15.03.2014, 01:34 | Сообщение # 6184 |
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| tcsgroupe | Дата: Понедельник, 17.03.2014, 05:01 | Сообщение # 6185 |
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| GW501516 (also known as GW-501,516, GW1516, GSK-516 and Endurobol<> - ) is a PPARδ receptor agonist that was previously investigated in search stimulant avail oneself of before GlaxoSmithKline. The narcotize was discovered to prime mover cancer in rats and GlaxoSmithKline has ceased development.<> - <> - It activates the same pathways activated including exercise, including PPARδ and AMP-activated protein kinase. It had been investigated as a budding treatment for avoirdupois, diabetes, dyslipidemia and cardiovascular disease.<> - <> - GW501516 has a synergistic sense when combined with AICAR: the grouping has been shown to significantly multiply exercise stick-to-it-iveness in animal studies more than either compound alone.<> - <> -
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GW501516 was initially discovered during a study collaboration between GSK and Ligand Pharmaceuticals that began in 1992.<> - R & D Hub Medicine Newsflash reported that GSK began step I trials of the compound against the treatment of hyperlipidemia in 2000<>0 - followed via phase I/II in 2002.<>1 - The disclosure of the worsen was published in a 2001 issue of PNAS.<>2 - Oliver et al. reported that they familiar "combinatorial chemistry and structure-based numb lay out" to come out it.<>3 - Limerick of the authors was the son of Leo Sternbachwho discovered benzodiazepines in the 1960s.<>4 - In 2003, Ligand Pharmaceuticals earned a $1 million payment as a consequence of GSK continuing phase I development.<>5 -
GW501516 had completed two status II clinical studies but GSK unrestrained to a greater distance development of the cure-all in 2007 in the interest reasons which where not disclosed as of 2008.<>6 -
Ronald M. Evans from the Salk Organize wishes to imagine the "first-ever performance-enhancing drug that can radically moreover medical man durability in humans". In 2004 he had showed that mice genetically engineered to swift PPARδ in muscle cells had greater endurance. He called the mice "marathon mice".<>7 - <>8 - He purchased a taste of GW501516 and gave mice a much higher dispense than had been in dig into by GSK and start that the come increased the patience of the mice. The probing culminated in a 2007 thesis inCell that was widely reported in the all the rage press including The Unfamiliar York Times and The Enrage fail High road Journal.<>7 -
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| gosgocas | Дата: Вторник, 18.03.2014, 12:58 | Сообщение # 6186 |
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| tcsgroupf | Дата: Вторник, 18.03.2014, 13:24 | Сообщение # 6187 |
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It is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese filth test that contained the bacteria Streptomyces tsukubaensis. It reduces interleukin-2 (IL-2) production during T-cells.
Olden days
Tacrolimus was discovered in 1984; it was middle the opening macrolide immunosuppressants discovered, preceded near the development of rapamycin (sirolimus) on Rapa Nui (Easter Atoll) in 1975.<> - It is produced by way of a type of stain bacterium,Streptomyces tsukubaensis.<> - The handle tacrolimus is derived from 'Tsukuba macrolide immunosuppressant'.<> -
Tacrolimus was to begin approved by means of the Edibles and Cure-all Superintendence (FDA) in 1994 someone is concerned end in liver transplantation; this has been extended to embrace kidney, heart, reduced bowel, pancreas, lung, trachea, pellicle, cornea, bone marrow, and limb transplants.
Availability
The branded variation of the drug is owned by Astellas Pharma, and is sold under the vocation names Prograf assumed twice daily,Advagraf, a unceasing unfetter formulation allowing a single time finally daily dosing, and Protopic (Eczemus in Pakistan by Brookes Pharma), the up to date formulation.<> - Advagraf is available in 0.5, 1, 3 and 5 mg capsules, the not bad is concentrations of 0.1% and 0.03%.
A number two once-daily formulation of tacrolimus is in Stage 3 clinical trials in the U.S. and Europe. This formulation also has a smoother pharmacokinetic limn gross that reduces the peak-to-trough rank in blood levels compared to twice-daily tacrolimus.<> - Materials from the premier Viewpoint 3 contest in deep-rooted kidney transfer patients showed that this once-daily formulation was non-inferior in efficacy and sanctuary compared to twice-daily tacrolimus.<> - A second Phase 3 litigation in de novo patients is ongoing.<> -
Monism of encounter
Tacrolimus is chemically known as a macrolide. In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to get started calcineurin. Calcineurin then dephosphorylates the transcription element NF-AT (atomic aspect of activated T-cells), which moves to the nucleus of the T-cell and increases the activity of genes coding for IL-2 and related cytokines. Tacrolimus prevents the dephosphorylation of NF-AT.<> - In detachment, Tacrolimus reduces peptidyl-prolyl isomerase operation during binding to the immunophilin FKBP12 (FK506 binding protein) creating a new complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin therefore inhibiting both T-lymphocytesignal transduction and IL-2 transcription.<> - Although this activity is alike resemble to ciclosporin, studies secure shown that the incidence of keen repudiation is reduced by tacrolimus use over ciclosporin.<>0 - Although short-term immunosuppression concerning acquiescent and extortion survival is found to be be like between the two drugs, tacrolimus results in a more favorable lipid profile, and this may have substantial long-term implications fact the prognostic play of also brush on graft survival.<>1 -
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