40 replies to this topic

[tonyrx7]

I wonder how much of that SRT1720 or supplement equivalent a human will need to take to match 500 mg for mice to double their running distance?

http://nextbigfuture...-increased.html

September 29, 2009 Near Term Prospects for Increased Longevity NY Times: "In five or six or seven years," said Christoph Westphal, Sirtris co-founder [Sirtis was bought by GlaxoSmithKline for $720 million], "there will be drugs that prolong longevity." [H/T Michael Annisimov, Accelerating Future]

SRT-501, the company's special formulation of resveratrol, is being tested against two cancers, multiple myeloma and colon cancer that has spread to the liver. A chemical mimic of resveratrol, known as SRT-2104, is in a Phase 2 trial for Type 2 diabetes, and in a Phase 1 trial in elderly patients. (Phase 1 trials test for safety, Phase 2 for efficacy.)

Dr. Gallagher said that unpublished tests in mice showed that another chemical mimic, SRT-1720, increased both health and lifespan; after two years, twice as many mice taking the drug were alive compared with the undosed animals. Resveratrol itself has not been shown to increase lifespan in normal mice, although it does so in obese mice, laboratory roundworms and flies.

Sirtris has so far been doubly fortunate. No severe side effects have yet emerged from the clinical trials. The company has also been lucky in having apparently picked the right horse, or at least a good one, in a fast-developing field.

Sirtuins may not be the most important genes for longevity, Dr. Sinclair conceded at the conference, because the pathways controlled by the sirtuins, TOR and the others "all talk to each other, often by feedback loops."

Many theories of aging attribute senescence to the inexorable buildup of mutations in a person's DNA. Dr. Sinclair said that in his view "aging can be reversed" because the DNA mutations did not directly cause aging.

SRT1720 effect on mice

Mice without SRT1720 ran for roughly half a mile. Mice given 100 mg ran roughly seven-tenths of a mile. And mice on 500 mg of SRT1720 were able to run a full mile, twice the distance of untreated mice.

Here is an earlier article about Rapamycin being able to extend the lifespan of elderly mice by 9-13%. Rapamycin has known toxicities, such as fungal infections and pneumonia, the drug should not be taken by the general population as a kind of universal fountain of youth. So they need to find an equivalent to Rapamycin's positive effects and have them work in humans and not have the downsides.

SENS research and website

SENS is an acronym for "Strategies for Engineered Negligible Senescence". It is best defined as an integrated set of medical techniques designed to restore youthful molecular and cellular structure to aged tissues and organs. Essentially, this involves the application of regenerative medicine to the problem of age-related ill-health. However, regenerative medicine is usually thought of as encompassing a few specific technologies such as stem cell therapy and tissue engineering, whereas SENS incorporates a variety of other techniques to remove or obviate the accumulating damage of aging.

Currently, SENS comprises seven major types of therapy addressing seven major categories of aging damage, and you will find details of these therapies throughout this section of the website.

SENS Timeline and milestones

This is the first major SENS milestone, and I believe it will be achieved with laboratory mice. The degree of control that I consider sufficient is the ability to take a cohort of mice of a strain whose normal life expectancy is three years, do nothing to them until they are two years old, and get them to live an average of three more years, i.e., triple their remaining life expectancy. I often call this "Robust Mouse Rejuvenation," or RMR. My estimate for the time until this milestone is reached, if there is adequate funding, is ten years from now; almost certainly not as soon as seven years, but very likely to be less than 20 years. If funding is sluggish this could be doubled.

The second major SENS milestone, and it can reasonably be defined as the arrival of therapies that confer a postponement and repair of human aging proportional to that described for mice in milestone 1, i.e., a tripling of our remaining life expectancy with therapies initiated on our late fifties or so. Inevitably I call this "Robust Human Rejuvenation" or RHR.

My estimate for the time until this milestone is reached, starting from the time that the mouse target is achieved, is 15 years; almost certainly not as soon as five years, and could be as many as 100 years. Note that thistime I make no caveats about funding, because I think it is inconceivable that shortage of funds will be allowed to slow down this work once milestone 1 is achieved.

When we reach milestone 2, those with access to the relevant therapies will have an absolutely non-increasing risk of death per unit time — they will not age. This is because we will be identifying, characterising and solving aspects of aging that appear at progressively later ages, faster than they progress to a life-threatening state. We have no idea at present what we will need to do to keep 200-year-olds hale and hearty, but that's OK, because we won't need that information for at least another 100 years. If we just pay attention to things that begin to appear in 180-year-olds as soon as we have any, as well as in 80-year-old chimpanzees as soon as we have them, and given the amount of effort we'll be putting in, our chances of perpetually keeping one step ahead of the problem are very good.
At present, the risk of death per unit time that Westerners experience in their early teens is such that if it were maintained indefinitely we would live to around 1000 years on average. (This calculation has been done many times with different data and some people get 700, some 1200; 1000 is a fair consensus.)

So 9-13% improvement in the lifespan of elderly with a procedure that has side effects has been achieved in the lab. The first SENS goal is 300% improvement in the lifespan of elderly mice. There has been 0.1 to 0.2 years of improvement in lifespace enhancement in humans for decades because of the improved treatment of various diseases and general improvements in health. Individuals can choose a healthy lifestyle (exercise, proper diet, do not smoke) and have a good chance to increase their lifespan by ten years over not following a good lifestyle.

Edit: cleaned up formatting

Edited by niner, 30 September 2009 - 02:14 AM.

[maxwatt]

There is a lot in there. I've started by looking for Auwerx new paper on SRT1720, supposedly published this week in Cell Metabolism. It is not on the website, or in the TOC of the current issue (Sept 2). It may be that the October issue has not yet been published online, andthat is what they are referring to. Thee are a number of issues to clear up, and the paper will be needed.

First, the mice were given "500 mg of SRT1720". ? I assume per day, but 500 mg is a significant portion of a mouses's daily food intake. Did they mean 500 mg per kg? Without a pharmokineti study in humans vs mice for SRT1720, it is impossible to determine a human equivalence. FWIW, human atheletes here have reported noticeable increases in exercise endurance with resveratrol doses in a range between 500 mg and two grams.

If as posited, SRT1720 exerts its effects via SIRT1, then why did resveratrol not show a similar life-extending effect to SRT1720? Was the dose too low? This seems unlikely, as the mice in Auwerx earlier study on resveratrol showed market improvement in running time, though noseveral fold as stated in the news report. Perhaps the because CB57 strain of mice were "genetically messed up" as I suggested in a post a few months ago? But until the strain of mouse Auwerx used for SRT1720 is revealed, one cannot say.

The statement of Dr. Gallager of a significant increase in lifespan with SRT1720 could be very big news, though without more information it is possible it is only squaring the curve rather than increasing maximum survival time.


SRT1720 Structure

Attached Files

•  srt1720.gif   2.01KB   5 downloads

Edited by maxwatt, 29 September 2009 - 10:12 PM.

[opendoor]

FWIW, human atheletes here have reported noticeable increases in exercise endurance with resveratrol doses in a range between 500 mg and two grams.

Interesting updates.
Can you point to any athletes who have reported noticable increases in endurance at 500mg of resveratrol?

[maxwatt]

FWIW, human atheletes here have reported noticeable increases in exercise endurance with resveratrol doses in a range between 500 mg and two grams.

Interesting updates.
Can you point to any athletes who have reported noticable increases in endurance at 500mg of resveratrol?

Read through this thread Cyclist in Need of Mitochondrial Biogenesis

[opendoor]

Read through this thread Cyclist in Need of Mitochondrial Biogenesis

RideToLive"....they offered a 60 day supply for my testing of BF 500mg - Trans-resveratrol 98+% (RSV98). While they had been taking 1.5-2.0gms per day, I opted for a single 500mg dose accompanied by post workout meal. After 45 days, I can say I've had big gains, not reflective of any other training period since 1982-83 as a 24yo Cat II Racer. Hematocrit, Hemoglobin, and Cardiac Output remain unchanged from pre-RSV98 supplementation. however, the increased peripheral changes at the muscle are obvious, but still undocumented by biopsy."

I wonder what "obvious" is in his case.

velipimos: "I have to say I was blown away when I first started taking resveratrol at doses over 300mg in early 2007. It took me from an above average rider on my club rides to the best on most days. I have always believed it could have been a placebo effect but your experience tells me that it probably is not. I did not get a power meter until after supplementation so I have no hard data

"blown away" Strong language. Too bad he didn't quantify it either.


hedgehog:"It is really hard to judge... I believe it has made my climbing and endurance aspects better. I can ride for a hard 5 hours with minimal food and about 2 large water bottles (water only). My daily intake has varied a lot but typically 300-600mgs. I don't have any way to judge my cycling other then times and how well I feel.


This needs to be measured like the mice.

Edited by opendoor, 30 September 2009 - 03:46 AM.

[maxwatt]

...
This needs to be measured like the mice.

You asked "Can you point to any athletes who have reported noticable increases in endurance at 500mg of resveratrol?"

These athletes have done so. Ridetolive provided repeatable measurements on lab-quality equipment, which is head-and-shoulders above anecdotal reports. But even anecdotal reports lead to formation of a hypothesis. Based on that thread, I would be willing to bet that a double blind study will show that doses of resveratrol above 500 mg will show improvement in endurance in humans.

The scientific double-blind study is the highest standard of proof, but not the only valid one. We draw inferential conclusions from experience all the time.

[opendoor]

...
This needs to be measured like the mice.

You asked "Can you point to any athletes who have reported noticable increases in endurance at 500mg of resveratrol?"

These athletes have done so. Ridetolive provided repeatable measurements on lab-quality equipment, which is head-and-shoulders above anecdotal reports. But even anecdotal reports lead to formation of a hypothesis. Based on that thread, I would be willing to bet that a double blind study will show that doses of resveratrol above 500 mg will show improvement in endurance in humans.

The scientific double-blind study is the highest standard of proof, but not the only valid one. We draw inferential conclusions from experience all the time.

I meant athletes like the riders who were at 1.5-2g/day.
Resveratrol isn't new, so why haven't there been the double blind studies at 100mg, 500mg and 1500mg as has been conducted with running mice? After watching the mice on the treadmill run with twice the endurance, why is there so little curiosity among sccientists and sports doctors?

[niner]

Resveratrol isn't new, so why haven't there been the double blind studies at 100mg, 500mg and 1500mg as has been conducted with running mice? After watching the mice on the treadmill run with twice the endurance, why is there so little curiosity among sccientists and sports doctors?

Good question. I will hazard a guess that some racers are in fact using it, and not telling anyone. Not a win for science, but it might be a win for them.

[2tender]

There is curiosity, but I think its more important to think of Resveratrol in the context of good health and Life Extension, rather than another supplement that may enhance exercise ability. Most people taking high purity, non-compounded Resveratrol do experience an increase in stamina, this often translates to better exercise sessions, but I feel that is secondary to Resveratrol's primary effect ie. better health and life extension. Personally, I think anything over a gram of Resveratrol, for a person in reasonably good health, is not needed. We cannot discount the placebo effect, in these riders, nor can we ignore the possibility they were taking other supplements, a combination of which, may have been synergistic to the production of energy. Just my opinion.

[malbecman]

Good question. I will hazard a guess that some racers are in fact using it, and not telling anyone. Not a win for science, but it might be a win for them.

I'd go along with this thought as well. If these athletes have found something that works for them (whether physiologically real or placebo/mental edge), they are not
going to be blabbing about it. We're talking competitive people here, after all..... ;-)


edit for typos..

Edited by malbecman, 30 September 2009 - 11:43 PM.

[opendoor]

I'd go along with this thought as well. If these athletes have found something that works for them (whether physiologically real or placebo/mental edge), they are not
going to be blabbing about it. We're talking competitive people here, after all..... ;-)

But the news of resveratrol's stamina effect on mice is already two years old and not a secret to most in athletics. If they learn of a compound generally considered safe and may raise performance, there is a high incentive for many to try it as the two bikers did on the RideToLive thread.

One study could test bikers at certain distances, maybe on an inclined bike treadmill, and keep track of before and week 2 , week 4 results. Another study could test non athletes on a stair climber, etc.

I'd think a university sports department would have the resources for studies like this.

[VP.]

I agree that the absence of any athletic studies on resveratrol is curious. There are a number of studies on quercetin and the latest are conflicting. Why nothing on resveratrol? The fact that Lance Armstrong is pushing quercetin may have something to do with the increased interest. https://secure.frs.com/vip/qcopy/

BTW the latest study shows no effect on athletic performance for quercetin: http://www.scienceda...90903110820.htm
Here are the positive studies: https://secure.frs.c....2 abstract.pdf
https://secure.frs.c...ntificStudy.pdf

I have a reverence for the scientific process and I have not ruled out placebo effect for my results. Lets just say I'm intrigued and watching out for a real study.

[tom a]

I wonder how much of that SRT1720 or supplement equivalent a human will need to take to match 500 mg for mice to double their running distance?

.....

SRT1720 effect on mice

Mice without SRT1720 ran for roughly half a mile. Mice given 100 mg ran roughly seven-tenths of a mile. And mice on 500 mg of SRT1720 were able to run a full mile, twice the distance of untreated mice.

As I read the article you link to -- which dates back to Nov of 2008 -- the mice who achieved greater endurance running were being compared to mice who were fed a very rich diet. The SRT1720 groups were likewise fed the same rich diet, but put on far less weight. It's anybody's guess how much increased endurance may be due simply to differences in weight as opposed to other effects of SRT1720.

On the other hand, the NYTimes article on SRT1720 clearly states that, in Auxwerx' latest results, over twice as many normal mice have survived so far on SRT1720 when compared to a control group. That is obviously a result worth paying great attention to.

Personally, I'm a lot more interested in the results extending life and/or health than in improving athletic performance. Among other things, one is more likely to run longer distances alive than dead.

(Quick addition to original post) One other point. I'm struck by the quoted result -- that twice as many mice survive on SRT1720. Clearly this implies that half or more of the control mice have already died, by simple arithmetic. Given the general shape of those curves, it would suggest they are nearing the end of the range of lifespans for the control mice. Unless the numbers left are miniscule, so that having twice as many alive in the experimental group was not statistically significant, it would be pretty remarkable if the maximal lifespan was not greater for the experimental mice.

Edited by tom a, 01 October 2009 - 04:46 PM.

[tonyrx7]

Thanks tom_a and everybody for their input. I too like the delay of diseases and life extension part most. Since I'm not an athlete and my career doesn't depend on my performance, I see this as an added bonus. Forget steroids since there's already ways to detect it. Seems like SRT1720 might be the next prefer choice in the black market for sports if detection is not keeping up with technology.

[2tender]

Thanks tom_a and everybody for their input. I too like the delay of diseases and life extension part most. Since I'm not an athlete and my career doesn't depend on my performance, I see this as an added bonus. Forget steroids since there's already ways to detect it. Seems like SRT1720 might be the next prefer choice in the black market for sports if detection is not keeping up with technology.

No, that is absolutely not the case. First of all, Resveratrols affect on performance, of and by itself, is marginal at best and for some humans, non-existent at the least. It may be moderately helpful in combination with other supplements in the sense of providing more energy. To assert that SRT1720 is anabolic or performance enhancing, and about to be put on the black market is ridiculously ludicrous. Whatever data there is, is sparse and this derivative of Resveratrol could only be produced by a lab that has the most state-of-the-art equipment and best educated professionals. We are not talking flask and beaker, bathtub home brewing here. These SRT's are most likely to be cutting edge medicine that will win someone the Nobel prize, they are far from perfection yet and well safe guarded. Just my opinion.

[niner]

No, that is absolutely not the case. First of all, Resveratrols affect on performance, of and by itself, is marginal at best and for some humans, non-existent at the least. It may be moderately helpful in combination with other supplements in the sense of providing more energy. To assert that SRT1720 is anabolic or performance enhancing, and about to be put on the black market is ridiculously ludicrous. Whatever data there is, is sparse and this derivative of Resveratrol could only be produced by a lab that has the most state-of-the-art equipment and best educated professionals. We are not talking flask and beaker, bathtub home brewing here. These SRT's are most likely to be cutting edge medicine that will win someone the Nobel prize, they are far from perfection yet and well safe guarded. Just my opinion.

In some sports, more mitochondria may be a significant advantage, although I don't think it will make you stronger. It may be the case that highly trained athletes will already have more mitochondria, although from RidetoLive's posts, that sounds like it might not be the case. SRT1720 isn't likely to be something you can whip up in the kitchen, but the structure is published, so there are a LOT of chemists who could make it. In some parts of the world, I suspect that all you would need to do is show them the structure and show them the money...

[2tender]

No, that is absolutely not the case. First of all, Resveratrols affect on performance, of and by itself, is marginal at best and for some humans, non-existent at the least. It may be moderately helpful in combination with other supplements in the sense of providing more energy. To assert that SRT1720 is anabolic or performance enhancing, and about to be put on the black market is ridiculously ludicrous. Whatever data there is, is sparse and this derivative of Resveratrol could only be produced by a lab that has the most state-of-the-art equipment and best educated professionals. We are not talking flask and beaker, bathtub home brewing here. These SRT's are most likely to be cutting edge medicine that will win someone the Nobel prize, they are far from perfection yet and well safe guarded. Just my opinion.

In some sports, more mitochondria may be a significant advantage, although I don't think it will make you stronger. It may be the case that highly trained athletes will already have more mitochondria, although from RidetoLive's posts, that sounds like it might not be the case. SRT1720 isn't likely to be something you can whip up in the kitchen, but the structure is published, so there are a LOT of chemists who could make it. In some parts of the world, I suspect that all you would need to do is show them the structure and show them the money...

Well, if it is indeed that simple, then Sinclair and Glaxo have a lot of competition throughout the world. Its my understanding that this is a "race" in an even stronger sense than nuclear and space technology. Disease free ageing, hmmm, what could we do with that?

[opendoor]

Sinclair said on 60 Minutes that he thought SRT-1720 (or maybe some other pill) would be sold in "conservatively, 5 years" That would mean early 2014. Westphal was quoted in the New York Times that drugs to extend longevity would be available in 5 to 7 years, or late 2014 to 2016.

At this point, why would it take as long as 5 to 7 years? Is it possible that an Indian company will sell something like SRT 1720 in 2011 or 2012?

[2tender]

I dont think it wrong to speculate, but I would much rather use something that I knew was produced by Sinclair and his peers. Once it does hit the market Im sure there will other formulations to follow. SRT1720 is probably the genesis of the SRT's by Glaxo. O n the other hand, there are only few that know for sure. All the money and appearances on major network prime time television thats gone towards this simply cant be for naught. Can it?

[niner]

At this point, why would it take as long as 5 to 7 years? Is it possible that an Indian company will sell something like SRT 1720 in 2011 or 2012?

Not in America or Europe or Japan or Australia or anywhere else that GSK has patented 1720 they won't.

Well, if it is indeed that simple, then Sinclair and Glaxo have a lot of competition throughout the world. Its my understanding that this is a "race" in an even stronger sense than nuclear and space technology. Disease free ageing, hmmm, what could we do with that?

If it were like the space race, the government would be putting billions into it. They aren't. However, we just picked up five thousand dollars from 3banana.com... Aside from that, there's the issue of intellectual property laws. (See above) People can make it, but they can't openly sell it and remain legal. If you wanted a kilogram of 1720 for your own use, you could find a lab somewhere that would make it for you, but if you tried to market it, that would be a different story.

[2tender]

At this point, why would it take as long as 5 to 7 years? Is it possible that an Indian company will sell something like SRT 1720 in 2011 or 2012?

Not in America or Europe or Japan or Australia or anywhere else that GSK has patented 1720 they won't.

Well, if it is indeed that simple, then Sinclair and Glaxo have a lot of competition throughout the world. Its my understanding that this is a "race" in an even stronger sense than nuclear and space technology. Disease free ageing, hmmm, what could we do with that?

If it were like the space race, the government would be putting billions into it. They aren't. However, we just picked up five thousand dollars from 3banana.com... Aside from that, there's the issue of intellectual property laws. (See above) People can make it, but they can't openly sell it and remain legal. If you wanted a kilogram of 1720 for your own use, you could find a lab somewhere that would make it for you, but if you tried to market it, that would be a different story.

Interesting, I appreciate your comments, they help keep the perspective here. Five thousand from 3banana, its good news. Hopefully priorities will change soon. Disease free aging, virtual immortals, oh I see.... its only for the wealthy. On the other hand there are people that look forward to senility. Even at this early stage I dont think it has to be that way. It is work though, and experimentation, research, etc.

Edited by 2tender, 02 October 2009 - 11:31 PM.

[niner]

Interesting, I appreciate your comments, they help keep the perspective here. Five thousand from 3banana, its good news. Hopefully priorities will change soon. Disease free aging, virtual immortals, oh I see.... its only for the wealthy. On the other hand there are people that look forward to senility. Even at this early stage I dont think it has to be that way. It is work though, and experimentation, research, etc.

At this point it's not even for the wealthy. If we can get it to work for the wealthy, then it won't be too long before generic competition will be available to bring costs down. By the time a drug gets on the market, it usually has less than ten years of patent lifetime left. That's why today you can buy generic Claritin for about three cents a day, or a course of Prilosec for ten bucks; they are off patent. I don't know anyone who's looking forward to senility. Does it have to be this way? I don't know. When people try to reform the system, they get eaten alive politically. You'll have to fix that first.

[opendoor]

I'd rather take an FDA approved Glaxo pill over Dehli's Discounts, too, but who can stop the latter from making it in a couple of years if India won't have tougher intellectual property rights enforcement? Are HIV drugs easier to make?

[2tender]

Interesting, I appreciate your comments, they help keep the perspective here. Five thousand from 3banana, its good news. Hopefully priorities will change soon. Disease free aging, virtual immortals, oh I see.... its only for the wealthy. On the other hand there are people that look forward to senility. Even at this early stage I dont think it has to be that way. It is work though, and experimentation, research, etc.

At this point it's not even for the wealthy. If we can get it to work for the wealthy, then it won't be too long before generic competition will be available to bring costs down. By the time a drug gets on the market, it usually has less than ten years of patent lifetime left. That's why today you can buy generic Claritin for about three cents a day, or a course of Prilosec for ten bucks; they are off patent. I don't know anyone who's looking forward to senility. Does it have to be this way? I don't know. When people try to reform the system, they get eaten alive politically. You'll have to fix that first.

I agree, but we are a democratic nation, not a nation that pretends to be democratic. Politicians that reform, know exactly what they are up against, and by increment America will get better. We have to believe and practice our freedom, harming none, and have as much integrity as possible. So when you get your 1720 please share,LOL

[2tender]

I'd rather take an FDA approved Glaxo pill over Dehli's Discounts, too, but who can stop the latter from making it in a couple of years if India won't have tougher intellectual property rights enforcement? Are HIV drugs easier to make?

Until and unless there are confirmed reports of purity in manufacturing, including anecdotal experiences and possible state side testing by importers, I wouldnt hazard it. The Resveratrol products we have here are probably the best available anywhere and people in decent to moderate health and age can probably benefit from them. As for 1720 and the other Srt's
hopefully we wont need them till the 70's or 80's.

Edited by 2tender, 03 October 2009 - 12:46 AM.

[stevei]

It is worth noting that a doubling of untrained endurance is not a particularly impressive achievement. From personal experience, with relatively modest amounts of training I am able to quadruple my untrained performance. E.g. if I consider swimming, my untrained maximal effort time for 100m becomes, with training, my maximal effort pace for 400m.

So if resveratrol can achieve a doubling for untrained people, this might correspond to the same benefit that they could get from training for a couple of hours a week, split into 4 x 30 minute sessions on 4 days of each week, say. I'm not saying this isn't a worthwhile benefit, but if this is all it did, it wouldn't be of much relevance to elite athletes.

What would be significant for elite athletes would be if resveratrol could achieve a further doubling on top of the maximum level an elite athlete could reach with training. As we haven't seen the World Record for Mens 400m freestyle drop 10 seconds to 3:30, I can only conclude that either a) resveratrol cannot achieve this, or b) no swimmer who can do 200m in 1:45 or faster has tried resveratrol, or c) perhaps it provides the benefit only to people who would otherwise not reach elite level.

C) would explain why we see anecdotal evidence of improvements without seeing World Records demolished. I find it quite plausible that it might be able to act to improve the function of people's bodies when they are in some sense dysfunctional compared to the best performing humans on the planet, while at the same time not being able to improve the function of those whose bodies are functioning as perfectly as any human's ever has.

[opendoor]

There is a lot in there. I've started by looking for Auwerx new paper on SRT1720, supposedly published this week in Cell Metabolism. It is not on the website, or in the TOC of the current issue (Sept 2). It may be that the October issue has not yet been published online, andthat is what they are referring to. Thee are a number of issues to clear up, and the paper will be needed.

Anyone know when this paper will be out?

Also, does anyone know the difference between SRT1720 and SRT2041? Why would Auwerx be testing that while Sirtris only has SRT501 and SRT2041 in trials?


I'll take my questions off the air....

[niner]

Also, does anyone know the difference between SRT1720 and SRT2041? Why would Auwerx be testing that while Sirtris only has SRT501 and SRT2041 in trials?

1720 might have a known liability that prevents it from being the candidate to move forward for human trials, though it still may be an interesting tool compound. If 2041 is going in humans, they may not want to do any experiments with it for fear of raising any troublesome issues. For example, if they were to put a compound into a type of mouse that usually dies of cancer, and most of the mice die of cancer as usual, then years later when that compound had been in humans for a long time, and some of those humans coincidentally got cancer at a later date, a lawyer who got hold of the mouse data could wave it in front of a jury and say "See, they knew it caused cancer, and still they sold it!!" And there's a billion dollar jury award.

[maxwatt]

There is a lot in there. I've started by looking for Auwerx new paper on SRT1720, supposedly published this week in Cell Metabolism. It is not on the website, or in the TOC of the current issue (Sept 2). It may be that the October issue has not yet been published online, andthat is what they are referring to. Thee are a number of issues to clear up, and the paper will be needed.

Anyone know when this paper will be out?

Also, does anyone know the difference between SRT1720 and SRT2041? Why would Auwerx be testing that while Sirtris only has SRT501 and SRT2041 in trials?


I'll take my questions off the air....

Good questions. I may be off-base, but they seem to be both using a nitrogen atom to change the angle between the rings with the OH groups critical for binding to SIRT1, to get a better conformational docking to the SIRT1 molecule; it's more likely to bind, and/or binds more strongly. They worked from models of SIRT1, and my understanding is the main difficulty in their approach was finding a stable molecule that would do this. However,the angle for SIRT1 is different than for the other six human sirtuins, so these comppounds may not be any better except to treat the conditions SIRT1 s involved with. A published table in Nature showed SRT1720 was no better than resveratrl for SIRT2 or 3, I forget which, probably 3.

[opendoor]

There is a lot in there. I've started by looking for Auwerx new paper on SRT1720, supposedly published this week in Cell Metabolism. It is not on the website, or in the TOC of the current issue (Sept 2). It may be that the October issue has not yet been published online, andthat is what they are referring to.

October is running out... the November issue?