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GW-501516
(also known as GW-501,516,GW1516 or GSK-516) is a PPAR***948; modulator compound being investigated for drug use by GlaxoSmithKline.[1][2] It activates the same pathways activated through exercise, including PPAR***948; and AMP-activated protein kinase. It is being investigated as a potential treatment for obesity, diabetes, dyslipidemia and cardiovascular disease. [3] [4] GW-501516 has a synergistic effect when combined with AICAR: the combination has been shown to significantly increase exercise endurance in animal studies more than either compound alone. [5][6]
GW-50156 regulates fat burning through a number of widespread mechanisms [7]; it increases glucose uptake in skeletal muscle tissue and increases muscle gene expression, especially genes involved in preferential lipid utilization.,[8][9] [10] This shift changes the body's metabolism to favor burning fat for energy instead of carbohydrates or muscle protein, potentially allowing clinical application for obese patients to lose fat effectively without experiencing muscle catabolism or the effects and satiety issues associated with low blood sugar. [11] GW-501516 also increases muscle mass, which improved glucose tolerance and reduced fat mass accumulation even in mice fed a very high fat diet, suggesting that GW-501516 may have a protective effect against obesity [12]
It has been demonstrated at oral doses of 5 mg a day to reverse metabolic abnormalities in obese men with pre-diabetic metabolic syndrome, most likely by stimulating fatty acid oxidation.[13] Treatments with GW-501516 have been shown to increase HDL cholesterol by up to 79% in rhesus monkeys and the compound is now undergoing Phase II trials to improve HDL cholesterol in humans. [14]
Concerns were raised prior to the 2008 Beijing Olympics that GW-501516 could be used by athletes as a performance enhancing drug which was not currently controlled by regulations or detected by standard tests. One of the main researchers from the study on enhanced endurance consequently developed a urine test to detect the drug, and made it available to the International Olympic Committee.[15] The World Anti-Doping Agency has also begun work on a test GW-501516 and other related PPAR***948; modulators.,[16] and they have been added to the prohibited list from 2009 onwards.[17] The compound has yet to be named a controlled or prohibited substance by any nation's drug enforcement or regulation agency. To date, no athlete is known to have tested positive for the substance, though the increase in endurance, muscle fiber performance, fat loss and metabolism suggests GW-501516 has the potential for ergogenic use and abuse.
"GW501516" - Reduces fat & greatly produces slow twitch muscle
Mice which can run almost twice the distance of normal mice have been genetically engineered by US scientists.
"This is the first animal engineered for increased endurance," says Ronald Evans of the Salk Institute in La Jolla, California, whose team created the mice.
But Evans adds that the work also suggests that drugs already in clinical development may, unintentionally, boost endurance. "The potential for this to be abused by athletes is real," he points out.
Pills that mimic the benefit of exercise could also help patients whose conditions prevent them from exercising and building muscle, such as people suffering from obesity. In fact, it was while studying genes involved in obesity and fat metabolism that Evans's team stumbled across how to make mice long distance runners.
The focus of their work was a protein called PPARdelta, known to play a role in promoting the burning of fat and fighting obesity.
In previous work, his team has shown that increasing the activity of PPARdelta in fat cells encourages cells to reduce their fat stores. In the body, however, the greatest consumer of fat is slow twitch muscle, the type of muscle that gives athletes endurance. The other major type of muscle is fast twitch which is powered mainly by sugar and is responsible for strength and rapid reaction.
Conditioned athletes
So Evans's team genetically-engineered mice to produce extra PPARdelta in their muscle. As expected, when these engineered mice and control mice were put on a high fat diet for 97 days, the engineered mice experience only one-third of the weight gain that controls did.
But to the researchers' surprise, increasing PPARdelta also had a dramatic effect on the muscle composition itself: it doubled the amount of slow twitch muscle.
"These mice are genetically in better shape. They behave like conditioned athletes," says Evans. When tested, the marathon mice were able to run 92 per cent longer than normal controls.
It is unclear whether boosting PPARdelta levels later in life - or in people - would similarly enhance endurance. But, by coincidence, a drug called GW501516 which activates PPARdelta directly - is being clinically tested as a treatment to lower blood cholesterol and fat by the pharmaceutical company GlaxoSmithKline.
Evans has already shown the new drug causes many of the same genetic changes in muscle cells triggered by increasing levels of PPARdelta protein.
Therapeutic purposes
The question that remains is whether the drug alone will be enough to increase endurance "I suspect that animals training with the drug will increase endurance more rapidly," predicts Evans.
Evans says he has no affiliation with GlaxoSmithKline. And the company has so far been able to provide any comment on the work.
Farnaz Khadem, a spokesperson for the World Anti-Doping Agency, which strives to make sporting competitions drug-free, says she would not be surprised if cheating athletes would try taking GW501516, if it becomes available.
"Most doping involves a substance developed for therapeutic purposes being used for a sports purpose," she says. "Medical science is moving forward, which is good. But it also means we've got to be on our toes."
(source: GM 'marathon' mice break distance records - 23 August 2004 - New Scientist )
here is a link just in case this is hard to read
GW501516 In Subjects Who Have Low Level Of High-Density Lipoprotein Cholesterol - Full Text View - ClinicalTrials.gov
GW501516 In Subjects Who Have Low Level Of High-Density Lipoprotein Cholesterol
This study has been completed.
First Received on September 8, 2005. Last Updated on March 17, 2011 History of Changes
Sponsor: GlaxoSmithKline
Information provided by: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00158899
Purpose
The purpose of this clinical research study is to compare up to 3 doses of an investigational drug GW501516 to placebo (an inactive pill that looks like GW501516) to see if it is safe, well tolerated and effective in improving (raising) low levels of "good cholesterol", high-density lipoprotein cholesterol (HDLc), as compared to placebo.
Condition Intervention Phase
Dyslipidaemias
Dyslipidaemia
Drug: GW501516 oral tablets
Phase II
Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: See Detailed Description
Resource links provided by NLM:
MedlinePlus related topics: Cholesterol
Drug Information available for: GW501516
U.S. FDA Resources
Further study details as provided by GlaxoSmithKline:
Primary Outcome Measures:
* The change from baseline in fasting plasma HDLc concentration at the end of 12 weeks of double-blind treatment. [ Time Frame: 12 Weeks ]
Secondary Outcome Measures:
* Changes from baseline at the end of 12 weeks of double-blind treatment of total cholesterol and other lipid parameters. Population pharmacokinetic parameters including oral clearance and apparent volume of distribution of GW501516. [ Time Frame: 12 Weeks ]
Enrollment: 424
Study Start Date: August 2004
Intervention Details:
Drug: GW501516 oral tablets
Other Name: GW501516 oral tablets
Detailed Description:
A multicentre, two-staged with interim analysis, parallel, randomised, double blind, placebo-controlled, dose-ranging study of the safety, tolerability, and effects on plasma high-density lipoprotein cholesterol (HDLc) of 12 weeks treatment with 2.5mg, 5mg and 10mg daily doses of GW501516 in subjects with low HDLc
Eligibility
Ages Eligible for Study: 18 Years to 75 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Inclusion criteria:
* Have a fasting plasma HDLc concentration <=45mg/dL (<=1.16mmol/L), plasma LDLc levels that do not require treatment according to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPÂ III) guidelines.
* Have a fasting plasma TG concentration =500mg/dL (=5.65mmol/L).
Exclusion criteria:
* Coronary heart disease.
* Diabetes mellitus.
* Atherosclerotic disease.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00158899
Show 64 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MA GlaxoSmithKline
More Information
No publications provided
Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00158899 History of Changes
Other Study ID Numbers: PAD20001
Study First Received: September 8, 2005
Last Updated: March 17, 2011
Health Authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Keywords provided by GlaxoSmithKline:
HDLc
high-density lipoprotein
Dyslipidemia
Additional relevant MeSH terms:
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
ClinicalTrials.gov processed this record on November 03, 2011
here is a list of studies if you want to google them
Product Literature References
Activation of peroxisome proliferator-activated receptor-{delta} by GW501516 prevents fatty acid-induced nuclear factor-{kappa}B activation and insulin resistance in skeletal muscle cells: T. Coll, et al.; Endocrinology 151, 1560 (2010), Abstract;
Activation of PPARdelta promotes mitochondrial energy metabolism and decreases basal insulin secretion in palmitate-treated beta-cells: L. Jiang, et al.; Mol.Cell Biol. (2010), Abstract;
Cross-talk between vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling in melanoma cells: P. Sertznig, et al.; Anticancer Res. 29, 3647 (2009), Abstract;
Effects of the PPAR-beta agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination: A. Defaux, et al.; J. Neuroinflammation 6, (2009), Abstract;
Determination of the critical amino acids involved in the peroxisome proliferator-activated receptor (PPAR) delta selectivity of phenylpropanoic acid-derived agonists: J. Kasuga, et al.; Chem. Med. Chem. 3, 1662 (2008), Abstract;
A short and efficient synthesis of the pharmacological research tool GW501516 for the peroxisome proliferator-activated receptor delta: Z.L. Wei & A.P. Kozikowski; J. Org. Chem. 68, 9116 (2003), Abstract;
Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)-synthesis and biological activity: M.L. Sznaidman, et al.; Bioorg. Med. Chem. Lett. 13, 1517 (2003), Abstract;
Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism: A.J. Gilde, et al.; Circ. Res. 92, 518 (2003), Abstract;
Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity: Y.X. Wang, et al.; Cell 113, 159 (2003), Abstract;
PPARdelta activation induces COX-2 gene expression and cell proliferation in human hepatocellular carcinoma cells: B. Glinghammar, et al.; BBRC 308, 361 (2003), Abstract;
The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells: U. Dressel, et al.; Mol. Endocrinol. 17, 2477 (2003), Abstract;
A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport: W.R. Oliver, Jr., et al.; PNAS 98, 5306 (2001), Abstract; Full Text
(also known as GW-501,516,GW1516 or GSK-516) is a PPAR***948; modulator compound being investigated for drug use by GlaxoSmithKline.[1][2] It activates the same pathways activated through exercise, including PPAR***948; and AMP-activated protein kinase. It is being investigated as a potential treatment for obesity, diabetes, dyslipidemia and cardiovascular disease. [3] [4] GW-501516 has a synergistic effect when combined with AICAR: the combination has been shown to significantly increase exercise endurance in animal studies more than either compound alone. [5][6]
GW-50156 regulates fat burning through a number of widespread mechanisms [7]; it increases glucose uptake in skeletal muscle tissue and increases muscle gene expression, especially genes involved in preferential lipid utilization.,[8][9] [10] This shift changes the body's metabolism to favor burning fat for energy instead of carbohydrates or muscle protein, potentially allowing clinical application for obese patients to lose fat effectively without experiencing muscle catabolism or the effects and satiety issues associated with low blood sugar. [11] GW-501516 also increases muscle mass, which improved glucose tolerance and reduced fat mass accumulation even in mice fed a very high fat diet, suggesting that GW-501516 may have a protective effect against obesity [12]
It has been demonstrated at oral doses of 5 mg a day to reverse metabolic abnormalities in obese men with pre-diabetic metabolic syndrome, most likely by stimulating fatty acid oxidation.[13] Treatments with GW-501516 have been shown to increase HDL cholesterol by up to 79% in rhesus monkeys and the compound is now undergoing Phase II trials to improve HDL cholesterol in humans. [14]
Concerns were raised prior to the 2008 Beijing Olympics that GW-501516 could be used by athletes as a performance enhancing drug which was not currently controlled by regulations or detected by standard tests. One of the main researchers from the study on enhanced endurance consequently developed a urine test to detect the drug, and made it available to the International Olympic Committee.[15] The World Anti-Doping Agency has also begun work on a test GW-501516 and other related PPAR***948; modulators.,[16] and they have been added to the prohibited list from 2009 onwards.[17] The compound has yet to be named a controlled or prohibited substance by any nation's drug enforcement or regulation agency. To date, no athlete is known to have tested positive for the substance, though the increase in endurance, muscle fiber performance, fat loss and metabolism suggests GW-501516 has the potential for ergogenic use and abuse.
"GW501516" - Reduces fat & greatly produces slow twitch muscle
Mice which can run almost twice the distance of normal mice have been genetically engineered by US scientists.
"This is the first animal engineered for increased endurance," says Ronald Evans of the Salk Institute in La Jolla, California, whose team created the mice.
But Evans adds that the work also suggests that drugs already in clinical development may, unintentionally, boost endurance. "The potential for this to be abused by athletes is real," he points out.
Pills that mimic the benefit of exercise could also help patients whose conditions prevent them from exercising and building muscle, such as people suffering from obesity. In fact, it was while studying genes involved in obesity and fat metabolism that Evans's team stumbled across how to make mice long distance runners.
The focus of their work was a protein called PPARdelta, known to play a role in promoting the burning of fat and fighting obesity.
In previous work, his team has shown that increasing the activity of PPARdelta in fat cells encourages cells to reduce their fat stores. In the body, however, the greatest consumer of fat is slow twitch muscle, the type of muscle that gives athletes endurance. The other major type of muscle is fast twitch which is powered mainly by sugar and is responsible for strength and rapid reaction.
Conditioned athletes
So Evans's team genetically-engineered mice to produce extra PPARdelta in their muscle. As expected, when these engineered mice and control mice were put on a high fat diet for 97 days, the engineered mice experience only one-third of the weight gain that controls did.
But to the researchers' surprise, increasing PPARdelta also had a dramatic effect on the muscle composition itself: it doubled the amount of slow twitch muscle.
"These mice are genetically in better shape. They behave like conditioned athletes," says Evans. When tested, the marathon mice were able to run 92 per cent longer than normal controls.
It is unclear whether boosting PPARdelta levels later in life - or in people - would similarly enhance endurance. But, by coincidence, a drug called GW501516 which activates PPARdelta directly - is being clinically tested as a treatment to lower blood cholesterol and fat by the pharmaceutical company GlaxoSmithKline.
Evans has already shown the new drug causes many of the same genetic changes in muscle cells triggered by increasing levels of PPARdelta protein.
Therapeutic purposes
The question that remains is whether the drug alone will be enough to increase endurance "I suspect that animals training with the drug will increase endurance more rapidly," predicts Evans.
Evans says he has no affiliation with GlaxoSmithKline. And the company has so far been able to provide any comment on the work.
Farnaz Khadem, a spokesperson for the World Anti-Doping Agency, which strives to make sporting competitions drug-free, says she would not be surprised if cheating athletes would try taking GW501516, if it becomes available.
"Most doping involves a substance developed for therapeutic purposes being used for a sports purpose," she says. "Medical science is moving forward, which is good. But it also means we've got to be on our toes."
(source: GM 'marathon' mice break distance records - 23 August 2004 - New Scientist )
here is a link just in case this is hard to read
GW501516 In Subjects Who Have Low Level Of High-Density Lipoprotein Cholesterol - Full Text View - ClinicalTrials.gov
GW501516 In Subjects Who Have Low Level Of High-Density Lipoprotein Cholesterol
This study has been completed.
First Received on September 8, 2005. Last Updated on March 17, 2011 History of Changes
Sponsor: GlaxoSmithKline
Information provided by: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00158899
Purpose
The purpose of this clinical research study is to compare up to 3 doses of an investigational drug GW501516 to placebo (an inactive pill that looks like GW501516) to see if it is safe, well tolerated and effective in improving (raising) low levels of "good cholesterol", high-density lipoprotein cholesterol (HDLc), as compared to placebo.
Condition Intervention Phase
Dyslipidaemias
Dyslipidaemia
Drug: GW501516 oral tablets
Phase II
Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: See Detailed Description
Resource links provided by NLM:
MedlinePlus related topics: Cholesterol
Drug Information available for: GW501516
U.S. FDA Resources
Further study details as provided by GlaxoSmithKline:
Primary Outcome Measures:
* The change from baseline in fasting plasma HDLc concentration at the end of 12 weeks of double-blind treatment. [ Time Frame: 12 Weeks ]
Secondary Outcome Measures:
* Changes from baseline at the end of 12 weeks of double-blind treatment of total cholesterol and other lipid parameters. Population pharmacokinetic parameters including oral clearance and apparent volume of distribution of GW501516. [ Time Frame: 12 Weeks ]
Enrollment: 424
Study Start Date: August 2004
Intervention Details:
Drug: GW501516 oral tablets
Other Name: GW501516 oral tablets
Detailed Description:
A multicentre, two-staged with interim analysis, parallel, randomised, double blind, placebo-controlled, dose-ranging study of the safety, tolerability, and effects on plasma high-density lipoprotein cholesterol (HDLc) of 12 weeks treatment with 2.5mg, 5mg and 10mg daily doses of GW501516 in subjects with low HDLc
Eligibility
Ages Eligible for Study: 18 Years to 75 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Inclusion criteria:
* Have a fasting plasma HDLc concentration <=45mg/dL (<=1.16mmol/L), plasma LDLc levels that do not require treatment according to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPÂ III) guidelines.
* Have a fasting plasma TG concentration =500mg/dL (=5.65mmol/L).
Exclusion criteria:
* Coronary heart disease.
* Diabetes mellitus.
* Atherosclerotic disease.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00158899
Show 64 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MA GlaxoSmithKline
More Information
No publications provided
Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00158899 History of Changes
Other Study ID Numbers: PAD20001
Study First Received: September 8, 2005
Last Updated: March 17, 2011
Health Authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Keywords provided by GlaxoSmithKline:
HDLc
high-density lipoprotein
Dyslipidemia
Additional relevant MeSH terms:
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
ClinicalTrials.gov processed this record on November 03, 2011
here is a list of studies if you want to google them
Product Literature References
Activation of peroxisome proliferator-activated receptor-{delta} by GW501516 prevents fatty acid-induced nuclear factor-{kappa}B activation and insulin resistance in skeletal muscle cells: T. Coll, et al.; Endocrinology 151, 1560 (2010), Abstract;
Activation of PPARdelta promotes mitochondrial energy metabolism and decreases basal insulin secretion in palmitate-treated beta-cells: L. Jiang, et al.; Mol.Cell Biol. (2010), Abstract;
Cross-talk between vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling in melanoma cells: P. Sertznig, et al.; Anticancer Res. 29, 3647 (2009), Abstract;
Effects of the PPAR-beta agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination: A. Defaux, et al.; J. Neuroinflammation 6, (2009), Abstract;
Determination of the critical amino acids involved in the peroxisome proliferator-activated receptor (PPAR) delta selectivity of phenylpropanoic acid-derived agonists: J. Kasuga, et al.; Chem. Med. Chem. 3, 1662 (2008), Abstract;
A short and efficient synthesis of the pharmacological research tool GW501516 for the peroxisome proliferator-activated receptor delta: Z.L. Wei & A.P. Kozikowski; J. Org. Chem. 68, 9116 (2003), Abstract;
Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)-synthesis and biological activity: M.L. Sznaidman, et al.; Bioorg. Med. Chem. Lett. 13, 1517 (2003), Abstract;
Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism: A.J. Gilde, et al.; Circ. Res. 92, 518 (2003), Abstract;
Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity: Y.X. Wang, et al.; Cell 113, 159 (2003), Abstract;
PPARdelta activation induces COX-2 gene expression and cell proliferation in human hepatocellular carcinoma cells: B. Glinghammar, et al.; BBRC 308, 361 (2003), Abstract;
The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells: U. Dressel, et al.; Mol. Endocrinol. 17, 2477 (2003), Abstract;
A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport: W.R. Oliver, Jr., et al.; PNAS 98, 5306 (2001), Abstract; Full Text
