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med chemist posting about SIRT and their Resveratrol


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#1 bixbyte

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Posted 03 March 2008 - 06:29 AM


borrowed from the yahoo finance Sirtris board:



I am a med chemist in the pharma industry. This company and their claims are the most puzzling I have

ever seen I have to conclude it is a scam.

1) resveratrol has been shown that it does not activate sirt1 enzyme in vitro, rather it is

artifactual activity which only occurs in the presence of a particular fluorophore labeled peptide

substrate. The activity isnt real. This has been published in Journal of Biological Chemistry, 2005,

17187 by Borra at the University of Wisconsin, Madison.

2) the data in the nature paper looks great, until you look at the underlying patents. First of all,

these patents were written so poorly that they will never be granted. Secondly, the med chem in these

patents looks like it was done by a rank amateur. These are not drugs. These compounds are garbage.

Again , it looks to me like they are chasing artifactual activity.


There is no way such a wide structural diversity of compounds could be active against any bio target.

The compounds claimed appear to be so electron rich, that they are probably not stable in air. I

suspect they are covalently modifying the sirt1 protein. Any chemist worth his salt would take one

look at these compounds and dismiss these claims as misconceptions of an inexperienced chemist at

best, or a complete fraud or scam at worst. These are not drugs. They are far, far from drugs. Any

company can pay to put anything in clinical trials, as long as it is not too toxic. That is what is

going on here. I have seen this many times before from small biotech companies. They put garbage into

clinical trials and see the cost as a necessary expense to boost the stock price. Then they hype the

claims, while they cash out themselves and run with the money, while the company crumbles under its

own weight. Run, run run away from this stock fast, before you are burned. Do not invest here. This

is a scam. I feel sorry for people who have invested here. This is psuedoscience. I hope these guys

go to jail!

______________________________________________________________

why are you are the only smart one here? Why when you are trying to help people by telling them the

problems with the claims of this company, they immediately turn it into a personal attack on you. I

did nothing against Yahoo policy. I am explaining the science that I know and comparing to the claims

of Sirtris. That is more "On Topic" than any other post on this board. Is not this what the board is

for? Would not investors want to hear from people who could explain what the probalems are for this

company, so they can make an educated decision to run with whatever money they have left now rather

than wait for the stock to crash?



_____________________________________

I dont give a shit about this stock. I am trying to help you guys by telling you what I know. This is

what I do for a living. I am a scientist. I know patent law and I know biology. I am writing here

because the claims of this company insult my sense of fair play and decency. Their patents were

written by rank amateurs, and for a small company, the most important asset is the patent estate.

Sirtris has nothing. And I am not making a personal attack on anybody here, I am trying to educate

you and realize your mistake before it is too late. You guys are surely quick to make personal

attacks on me when you dont like to hear what I am saying. I know that when somebody has bought into

a scam, even if they are smart educated people, it is the hardest thing to convince them that they

made a mistake. All I can say is download the patent applications for yourselves and take a look.

Compare them to patents of any major pharmaceutical company. Notice they have no granted patents,

only applications that will go nowhere. Read the Journal of Biological Chemistry paper on the

artifactual activity of resveratrol in the presence of Fluor-de-Lys peptide substrate. Keep an open

mind and try to gain understanding before you commit your money to this scam.

___________________________________________________




too bad you cant patent a natural product. This is not a drug, it is a food supplement , or something

that you would buy in a health food store. Anybody can by resveratrol cheap. It is a cheap chemical.

It is not a drug. So how does Sirtris make money off of a chemical commodity that anybody can buy and

sell? Dont get taken in by the scam.



________________________________________________________________________________
______



http://messages.fina...umview?bn=51605

see post: GNC-$20 a day resveratrol
by sirtiun [26-Feb-08 12:27 pm]

2-Mar-08 06:14 pm
by medchemist15

#2 niner

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Posted 03 March 2008 - 07:00 AM

The Fluor-de-Lys problem has been known for a long time- and this guy's claiming that it doesn't activate SirT1 in vitro? Not sure how he explains observed effects of res in vivo. He might be right about the NCEs being far far from drugs. Resveratrol is not the kind of molecule that a med chemist would consider a "good drug". If it was, you wouldn't need two to five grams a day. Still, he sounds like a bit of a crank. It's possible to work for a pharma company and still be a dope.

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#3 Hedgehog

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Posted 03 March 2008 - 07:15 AM

borrowed from the yahoo finance Sirtris board:





1) resveratrol has been shown that it does not activate sirt1 enzyme in vitro, rather it is

artifactual activity which only occurs in the presence of a particular fluorophore labeled peptide

substrate. The activity isnt real. This has been published in Journal of Biological Chemistry, 2005,

17187 by Borra at the University of Wisconsin, Madison.



Mechanism of Human SIRT1 Activation by Resveratrol*
Margie T. BorraPosted Image, Brian C. SmithPosted Image, and John M. DenuPosted Image
From the Departments of Posted ImageBiomolecular Chemistry and Posted ImageChemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706



Received for publication, February 2, 2005




Resveratrol Activates SIRT1 but Not Other Sir2 Homologs

CONCLUSIONS AND PERSPECTIVE
Resveratrol activated human SIRT1 but not other Sir2 homologs (yeast Sir2 and human SIRT2). Although activation was independent of peptide sequence, SIRT1 activation required a fluorophore-containing substrate. In the absence of resveratrol, the fluorophore impedes tight binding of the peptide to the enzyme. We propose that the binding of resveratrol to SIRT1 induces a conformational change in the enzyme which permits tighter fluorophore binding in the context of the entire peptide substrate. Our results have considerable implications for the general use of resveratrol as an in vivo activator of Sir2 homologs from a wide variety of organisms. In particular, because resveratrol activation appears to be specific for SIRT1, it would seem prudent to readdress the previously published studies linking yeast Sir2 and resveratrol to common cellular processes, such as life span increase via calorie restriction and gene silencing. Also, at this stage, it is unclear whether the fluorophore-specific activation of SIRT1 by resveratrol has revealed an intrinsic property of SIRT1. Resveratrol may serve as a mimic to endogenous regulators, which could alter SIRT1 structure and function, perhaps yielding an apparent "up-regulated" SIRT1. "Activated" SIRT1 may display altered specificity for a distinct acetylated substrate or may demonstrate a higher affinity for this target substrate. Because SIRT1 is reported to harbor no substrate selectivity on its own (<a href="http://www.jbc.org/c...17187#REF67">67), SIRT1 may need the help of an activator to take advantage of this inherent property and discriminate among possible substrate targets.

#4 bixbyte

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Posted 03 March 2008 - 08:05 AM

Resveratrol activated human SIRT1 but not other Sir2 homologs (yeast Sir2 and human SIRT2). Although activation was independent of peptide sequence, SIRT1 activation required a fluorophore-containing substrate. In the absence of resveratrol, the fluorophore impedes tight binding of the peptide to the enzyme. We propose that the binding of resveratrol to SIRT1 induces a conformational change in the enzyme which permits tighter fluorophore binding in the context of the entire peptide substrate. Our results have considerable implications for the general use of resveratrol as an in vivo activator of Sir2 homologs from a wide variety of organisms. In particular, because resveratrol activation appears to be specific for SIRT1, it would seem prudent to readdress the previously published studies linking yeast Sir2 and resveratrol to common cellular processes, such as life span increase via calorie restriction and gene silencing. Also, at this stage, it is unclear whether the fluorophore-specific activation of SIRT1 by resveratrol has revealed an intrinsic property of SIRT1. Resveratrol may serve as a mimic to endogenous regulators, which could alter SIRT1 structure and function, perhaps yielding an apparent "up-regulated" SIRT1. "Activated" SIRT1 may display altered specificity for a distinct acetylated substrate or may demonstrate a higher affinity for this target substrate. Because SIRT1 is reported to harbor no substrate selectivity on its own (67), SIRT1 may need the help of an activator to take advantage of this inherent property and discriminate among possible substrate targets.

#5 bixbyte

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Posted 03 March 2008 - 08:10 AM

Started posting 5:00 am sunday medchemist1 posts more at 3:00 am monday on the yahoo SIRT finance board:


I see. I am sad to see so much blatant fraud and deception going on in the stock market. And we complain about China. I know some of the insiders and I am pretty pissed off that they would do something like this. The end result will be that they will end up giving the pharmaceutical industry a bad name, even though they are just pharma wanna-bees. I know these guys know better. That is why I believe this is deliberate fraud. Not to mention the fact that they are all dumping their stock at $12 per share. A sign of how much confidence they have in the company.

#6 billypc99

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Posted 03 March 2008 - 05:34 PM

There is a large amount of truth to what this person in saying......The oringinal "sirtris" works were about 90% smoke and mirrors.....extremely misleading

#7 mikeinnaples

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Posted 03 March 2008 - 08:17 PM

Can we get a moderator to put a stop to yahoo board trash bringing it their crap over to these boards with them.

#8 sUper GeNius

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Posted 03 March 2008 - 09:10 PM

Can we get a moderator to put a stop to yahoo board trash bringing it their crap over to these boards with them.


+1

#9 drmz

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Posted 04 March 2008 - 06:27 AM

Can we get a moderator to put a stop to yahoo board trash bringing it their crap over to these boards with them.



I think it's interesting instead of crap . Think no mod is needed here

#10 mikeinnaples

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Posted 04 March 2008 - 01:25 PM

Can we get a moderator to put a stop to yahoo board trash bringing it their crap over to these boards with them.



I think it's interesting instead of crap . Think no mod is needed here



Most of us don't find trash spewed from a financial forum interesting, ESPECIALLY when it is from someone who is short in a stock and posts spam 24 hours a day under multiple identities.

I fail to see the value of that in these forums. Really, if you find it interesting, read the yahoo forums instead of bringing the yahoos here to this one.

#11 caston

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Posted 04 March 2008 - 03:17 PM

As immortalists though we will outlive stocks like this and fads like resveratrol.

#12 tintinet

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Posted 04 March 2008 - 06:32 PM

As immortalists though we will outlive stocks like this and fads like resveratrol.


Or die trying! ;)

#13 drmz

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Posted 04 March 2008 - 07:01 PM

Can we get a moderator to put a stop to yahoo board trash bringing it their crap over to these boards with them.



I think it's interesting instead of crap . Think no mod is needed here



Most of us don't find trash spewed from a financial forum interesting, ESPECIALLY when it is from someone who is short in a stock and posts spam 24 hours a day under multiple identities.

I fail to see the value of that in these forums. Really, if you find it interesting, read the yahoo forums instead of bringing the yahoos here to this one.



spamming is not interesting, discussion about their patents and studies is.

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#14 bixbyte

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Posted 04 March 2008 - 07:52 PM

http://biz.yahoo.com...05412.html?.v=1

Borrowed from the yahoo finance Sirtris board

medchemist response after sirtris drug study news:

Re: A single dose of SRT501 4-Mar-08 09:55 am

these are insiders. Why dont they disclose the structure so I can confirm the claims in my own lab? There are no claims that can be confirmed by independent labs because none of the structures have been disclosed in the published work.
________

1)I have never seen any of the fantastic claims of Sitris verified by any third party who were not on the payroll or who did not have massive stock holdings. Why do all of the compounds in the patents looks suspiciously like antioxidants?
2) Even if the claims were real, these compounds that I see in the patents are leads, not drugs. I dont think these kinds of compounds could ever become drugs because of their poor properties. You need to find some better leads.
3) They have no patent position on anything, just some very poorly written applications.

This reminds me of another company I saw a few years ago that sold zinc pills that were supposed to cure the comon cold. They were also talking about FDA trials and so forth, but like Sirtris, they had no patent position because the api was zinc. Like Sirtris, they also claimed they had a special proprietary formulation. Finally they boxed up their product in a flashy box and sold it in supermarkets and drug stores to cut their losses. If you call it a dietary supplement, then you dont need clinical trials. This is what Sirtris should do. Of course there were multiple competitor rip off products established almost immediately since they had no composition of matter patent, but they still made some money because they had the biggest and most colorful box and packaging. Stop trying to pretend you are a pharmaceutical company, get yourself a flashy box and packaging, and sell this stuff in the health food store as a cure-all. People will buy it and you will be able to show at least a small pittance of earnings to the stock holders.

Edited by bixbyte, 04 March 2008 - 08:00 PM.





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