GW-501516 Info on why you want it

Discussion in 'Peptides, IGF, HGH, Insulin' started by sniper33, Dec 9, 2012.

  1. sax

    sax VIP Member

    Jan 26, 2011
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    I will crack on them a little bit for cherry picking older positive studies and ignoring well published negative newer ones. Either don't cite sources leaving people to do their own research, or cite both. Don't cherry pick facts.
     
  2. Usealittle

    Usealittle VIP Member

    Feb 15, 2012
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    You do know you anyone can change info on wic.....
     
  3. sax

    sax VIP Member

    Jan 26, 2011
    118
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    Yes, I do know. That's why I continued researching until I found better info.
     
  4. sax

    sax VIP Member

    Jan 26, 2011
    118
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    Here is the what was said in 2009 by the Society of Toxicology in the link I previously provided. They have no stake in the game. I can edit Wiki, I can't edit this.

    895 RAT CARCINOGENICITY STUDY WITH GW501516, A PPAR DELTA AGONIST.
    L. E. Geiger1, W. S. Dunsford2, D. J. Lewis2, C. Brennan3, K. C. Liu3 and S. J. Newsholme1. 1Safety Assessment, GlaxoSmithKline, King of Prussia, PA, 2Safety Assessment, GlaxoSmithKline, Ware, United Kingdom and 3Huntingdon Life Sciences, Huntingdon, United Kingdom.
    GW501516, a non-genotoxic PPARδ agonist, was assessed for carcinogenic poten- tial by daily administration (oral gavage) to Han Wistar rats for a period of 104 weeks. Males were given 0, 5, 15 or 30 mg/kg/day for the first 6 weeks of the study. For the remainder of the study males were given 0, 5, 20 or 40 mg/kg/day. Females were given 0, 3, 10 or 20 mg/kg/day for the entire study. GW501516 produced test article-related neoplastic findings in multiple tissues at all doses. Increased mortal- ity was seen with females given GW501516 at all doses and uterine endometrial adenocarcinoma contributed to death in a high proportion of these animals. Neoplasms considered test-article related occurred in the liver (hepatocellular ade- noma at ≥ 10 mg/kg/day), urinary bladder (transitional cell carcinoma in males given 20 and 40 mg/kg/day), thyroid (follicular cell adenoma at ≥ 3 mg/kg/day and carcinoma in males at ≥ 20 mg/kg/day), tongue (squamous cell papilloma in males at 5 mg/kg/day and 40 mg/kg/day), stomach (squamous cell papilloma in males at ≥ 5 mg/kg/day and a female at 20 mg/kg/day, and carcinoma in a male at 40 mg/kg/day and a female at 3 mg/kg/day), skin (inverted squamous cell papilloma in males at ≥ 5 mg/kg/day and females at 3 or 20 mg/kg/day), Harderian glands (ade- noma in males at ≥ 5 mg/kg/day and adenocarcinoma in a male at 40 mg/kg/day), testes (interstitial cell adenoma at 40 mg/kg/day), ovary (Sertoli cell adenoma at ≥ 10 mg/kg/day) and uterus (polyp and endometrial adenocarcinoma at ≥ 3 mg/kg/day). Some of the tumor types observed in this study have not been reported with either PPARα or PPARγ agonists and may reflect tumor promotion mediated through PPARδ agonism.
     
    marx likes this.
  5. Go Away

    Go Away TID Board Of Directors

    Dec 28, 2011
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    wouldn't it suck to be the people in this study?! damn....
     
  6. sax

    sax VIP Member

    Jan 26, 2011
    118
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    They never made it past working on rats bro.
     
  7. Go Away

    Go Away TID Board Of Directors

    Dec 28, 2011
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    Sarcasm my dude. Was just playing
     
  8. sax

    sax VIP Member

    Jan 26, 2011
    118
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    Oh :) Gotcha.
     
  9. marx

    marx TID Board Of Directors

    Sep 29, 2010
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    Pretty eye opening, being on the leading edge of research can have it's pitfalls... The stuff looks to be poison, even if the athletic protocol is say 20mg a day for someone weighing 100 kilos it seems damn risky...

    Thanks for the studies, brother sax, much appreciation.
     
  10. Bilter

    Bilter VIP Member

    Jun 7, 2011
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    Reason for edit: study already posted on page 2
     
    Last edited: Mar 31, 2013
  11. Hanzo

    Hanzo VIP Member

    May 26, 2012
    35
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    The clinical research was flawed, FD 50 and less. GW HAS to be ran with AICAR or you might as well not run it. I've ran 2x with great results. These were evolved to be ran together from the very beginning. The doses given to rodents were as much as 1850gm's for crying out loud!!

    And yes, there is clinical research performed with human subjects. And yes, it did work with minimal sides. It's now being refered to as "cardio in a bottle".

    http://atvb.ahajournals.org/content/27/2/359.short
    Same study just condensed for some.
    http://atvb.ahajournals.org/content/32/9/2289.full

    Studies on animal subjects:

    http://www.ncbi.nlm.nih.gov/pubmed/21245211

    http://www.ncbi.nlm.nih.gov/pubmed/22908954

    http://www.ncbi.nlm.nih.gov/pubmed/18674809

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880836/table/T2/

    Here's a study with both rodent and human subjects. Seems we may have a resistance to the carcinogenesis displayed in rodents."As with any drug anticipated for chronic use in the treatment of metabolic disease, safety issues about PPARδ-targeted compounds have been raised. Particular attention has focused on a potential connection to carcinogenesis, since PPARδ was reported as a downstream target of the oncogenic Wnt/adenomatous polyposis coli (APC)/β-catenin pathway (78). A recent study disputes this connection, and further studies to decipher a role for PPARδ in cancer have been inconsistent (21, 7982). Experiments using PPARδ-null mice demonstrated that PPARδ is genetically dispensable for colon polyp formation in both the Apc[SUP]min[/SUP] genetic mutant and chemically induced colon cancer mouse models, and colon polyp formation was exacerbated in the genetic absence of PPARδ (21, 79, 80). Alternatively, xenografts of human colon cancer cells showed decreased tumorigenesis in cells somatically deleted of PPARδ, and treatment of Apc[SUP]min[/SUP] mice with high doses of the PPARδ ligand GW501516 yielded increases in the number and size of intestinal polyps (81, 82). Whether these ligand effects are truly dependent on PPARδ has not been established, and study using a PPARδ-null background is warranted. It is notable that synthetic PPARγ agonists, which have been extensively used in human subjects, enhance colon polyp formation in the Apc[SUP]min[/SUP] model yet have not been demonstrated to cause cancer in humans (83, 84). Similarly, PPARα activators cause hepatocarcinomas in rodents but fail to have such deleterious effects in humans. These findings cast doubt on the predictive power of mouse models to determine the human carcinogenicity of PPAR-targeted drugs". The 'evidence' that GW might play a role in lung cancer proliferation is being reversed now. In the study from pubmed says that even if GW puts off a cancer causing agent it's so small the body has it's own way of combatting and reducing any perceived threat.
     
    Last edited: May 26, 2014
  12. jhotsauce7

    jhotsauce7 TID Board Of Directors

    Jan 18, 2011
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    There's quite a bit of evidence purporting that PPAR agonists reduce cell proliferation in many different cell lines. In the essence GW may discourage carcinogenisis and regulate cellular production for many kinds of tissue.

    I think one study said that it did however cause cox-2 gene expression which can be a precursor to cancers, and thus it was suggested to take the drug with a cox-2 inhibitor.

    Other points of importance are the length of administration of the PPAR agonist in not just dose to mass relation but also in relation to lifespan, whereas the most commonly cited mouse and rat studies were for a period of 2 years (average rat or mouse lifespan is probably 3 years, so administration of this for 66% lifespan) and also it is important to point out that humans have a far greater cell differentiation and much more diverse cell lines than rodent subjects so this has also cast doubt that humans would see the same carcinogenic and cellular proliferating outcomes.

    Lastly I read in the most commonly sited study that GW501516 was administered in the study subsequent to administering a known carcinogen known as DBMA (7,12-Dimethylbenz[a]anthracene), which only when combined outside the control group with Carderide resulted in carcinogenisis in numerous tissue types for rodents.


    Here is some interesting reading material...

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171861/
     
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