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FOXO4 D-Retro-Inverso peptide group buy

foxo4

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#571 TaiChiKid

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Posted 24 July 2018 - 11:40 PM

My FOXO4 cane ub 10mg glass vials, rubber stopper sealed with a metal hold down wrap around.  Distinctive Genscript label (likely from their HK lab) with order # and lot #.  As I mentioned it has had a permanent effect (since July 1/2) dropping my Sys/Dias from Stage 1 hyper to borderline.hypertensive.  My other blood work will follow in the next few days.  I have no doubt it was genuine.



#572 smithx

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Posted 25 July 2018 - 07:27 AM

Not sure how one would prove identity and purity of this compound without a known-good sample to compare to. There's 0% chance that there's an existing spectrum for it in the MS databases.

 

Could you describe how the testing was actually accomplished?

 

 

I took 2 samples of 1mg each and sent them to a lab (found on ScienceExpress) for MS/MS analysis.  That added USD300 plus USD75 for shipping.


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#573 Madfern

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Posted 25 July 2018 - 08:13 AM

Not sure how one would prove identity and purity of this compound without a known-good sample to compare to. There's 0% chance that there's an existing spectrum for it in the MS databases.

 

Could you describe how the testing was actually accomplished?

 

I selected the lab based on their claim that they have had previous experience with the FOXO4-DRI peptide.

Based on my interpretation of the report and data received, the lab looks like being run by very experienced spectroscopists.  They also clarified a few questions I had about the data.

In the mass spectrum they identified various masses which are consistent with the total molecular weight of the peptide and various molecular fractions which are expected to dissociate at the different ionization energies.

They also identified that the peptide was in its crude form (not desalted) and that some fractions were present which are consistent with TFA residues.

 

A more comprehensive test would have also used LC at considerable additional costs.

The manufacturer supplied their own LC/MS-MS data for the batch which also was consistent with what the lab reported.

 

Of course all this is not absolute proof that the compound is FOXO4-DRI but the chances of another compound masquerading in such a consistent way with FOXO4 are pretty slim.

AFAIK, FOXO4 (L amino acids) and FOXO4-DRI (D amino acids) are probably indistinguishable by the tests done, but it would require a deliberate peptide design change by the manufacturer to produce FOXO4 instead of FOXO4-DRI.

 

Based on what I know at this time I am willing to take the risk.  If new evidence emerges I might change my mind.

Right now all of my FOXO4-DRI is in the freezer but I might do a trial with a small dose in the next few weeks.


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#574 smithx

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Posted 26 July 2018 - 12:23 AM

Actually you could just do the same peptide with L amino acids, which is much easier and trivial to do because it's a very well known technique. But the peptide would not be functional.

 

This is what I don't understand. The lab which created the peptide used in the published study (Pepscan) is perfectly willing to sell it. Their price is about 40% higher, but you know you are getting the real thing.

 

People taking this stuff are hoping it will rejuvenate them and perhaps increase their lifespan or at least healthspan. Why would anyone mess around with other suppliers to save a few dollars, not knowing that you're getting the actual compound that was studied?

 

 

Of course all this is not absolute proof that the compound is FOXO4-DRI but the chances of another compound masquerading in such a consistent way with FOXO4 are pretty slim.

AFAIK, FOXO4 (L amino acids) and FOXO4-DRI (D amino acids) are probably indistinguishable by the tests done, but it would require a deliberate peptide design change by the manufacturer to produce FOXO4 instead of FOXO4-DRI.

 

Based on what I know at this time I am willing to take the risk.  If new evidence emerges I might change my mind.

 


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#575 Madfern

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Posted 26 July 2018 - 01:14 AM

Actually you could just do the same peptide with L amino acids, which is much easier and trivial to do because it's a very well known technique. But the peptide would not be functional.

 

Making the peptide from L amino acids is not easier - it is exactly the same effort.

 

The mechanism of senescent cell clearance which we want to utilize here requires that the naturally occurring FOXO4 is replaced by the non-functioning FOXO4-DRI. 


Edited by Madfern, 26 July 2018 - 01:44 AM.

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#576 smithx

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Posted 26 July 2018 - 06:33 AM

Making the peptide from L amino acids is not easier - it is exactly the same effort.


Making retro-inverso peptides is much less common and is a different procedure. Since it's more common, it's easier to make L peptides.
 

The mechanism of senescent cell clearance which we want to utilize here requires that the naturally occurring FOXO4 is replaced by the non-functioning FOXO4-DRI.


More or less. The Foxo4 DRI binds to a site on P53 but doesn't cause the same inactivation of P53 that real Fox04 does. So we're not replacing it so much as displacing it at its active site on p53.

But all of this misses my point which again is:

 

Why would you try to save a few dollars by buying something you're not certain is real, especially when the stakes are so high (your life and health)?
 

 


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#577 Madfern

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Posted 26 July 2018 - 06:51 AM

Making retro-inverso peptides is much less common and is a different procedure. Since it's more common, it's easier to make L peptides.

 

let's just disagree on this point.

 

Why would you try to save a few dollars ...

 

I am not trying to save a few dollars.

The Chinese supplier was the only one I could find at the time.

I would be importing in any case with all the potential customs problems either from the US or from China.

 

 

... buying something you're not certain is real, ...

 

I am satisfied it is real -- you are entitled to you own opinion.

 

and from here on its  > /dev/null


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#578 extendcel

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Posted 26 July 2018 - 11:04 AM

Making retro-inverso peptides is much less common and is a different procedure. Since it's more common, it's easier to make L peptides.


More or less. The Foxo4 DRI binds to a site on P53 but doesn't cause the same inactivation of P53 that real Fox04 does. So we're not replacing it so much as displacing it at its active site on p53.

But all of this misses my point which again is:

Why would you try to save a few dollars by buying something you're not certain is real, especially when the stakes are so high (your life and health)?


No it is not easier, it is exactly the same procedure. While D amino acids may have slightly different biological properties, their chemical functionality is still the same as L amino acids.

Producing retro inverso peptides still uses solid phase synthesis, except you are using D amino acids instead of L. You still use the same protecting group as L amino acids which is usually Fmoc. The main difference is cost, but it doesn't make the synthesis easier or harder.

Also, FOXO4-DRI can be described as a competitive inhibitor of the FOXO4 protein by disrupting FOXO4-p53 interaction. The bound protein complex favors senescence while apoptosis is favored without this interaction. FOXO4-dri is a fragment that can bind to p53 but the complex itself is not active.
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#579 Cerebroo

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Posted 27 July 2018 - 10:13 PM

Hi, can anybody tell me where to buy the buffered saline for the peptide IN Europe? Or with normal shipping from the US? I am in spain.

 

Thx



#580 Michael

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Posted 27 July 2018 - 11:56 PM

 

Does the peptide you buy, contain the HIV-TAT sequence or not?

YES!
 
This is from the tat hiv wikipedia page
 
"Tat contains a protein transduction domain ... [which] allows Tat to enter cells by crossing the cell membrane. The amino acid sequence of the protein transduction domain is YGRKKRRQRRR.[...]  As of 2000 The biological role of this domain and exact mechanism of transfer is unknown [my emphasis]."
 
The FOXO4 DRI sequence is: ltlrkepaseiaqsileaysqngwanrrsggkrppp[/size]rrrqrrkkrg. The purple sequences matching up are going to be in reverse order.  This is a retro-inverso peptide so that means the sequence is reversed and the l amino acids are substituted with D amino acids. 
 
"Retro-inverso peptides are linear peptides whose amino acid sequence is reversed and the α-center chirality of the amino acid subunits is inverted as well. Usually, these types of peptides are designed by including D-amino acids in the reverse sequence to help maintain side chain topology similar to that of the original L-amino acid peptide and make them more resistant to proteolytic degradation." - biosyn.com

 

I apologize for coming in late and unfamiliar with which orders have and haven't been placed and with whom. But: while I won't say this dogmatically, it's certainly not clear to me that one should have the HIV-TAT sequence in retro-inverso form: it's not clear to me that de Keiser's FOXO4-DRI used a DRIHIV-TAT, and it still has to function as the native peptide does, unlike the FOXO4 sequence. "Modification of peptides to such a D-retro
inverso (DRI)-isoform can render peptides new chemical properties, which may improve their potency in vitro and in vivo (Borsello et al., 2003)."

 

I agree with Smithx that if it was me, I'd certainly prefer to buy from Pepscan than anyone else, especially some random contract lab in an emerging economy.


Edited by Michael, 28 July 2018 - 12:06 AM.


#581 Michael

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Posted 28 July 2018 - 03:01 AM

The leading theory on the cause of hair loss is that the cells of the dermal papilla are more likely to be senescent in people with male pattern baldness.

 

I don't think this is widely believed, although there are studies supporting a role for it. I think you're possibly confusing hair stem cell quiescence or hair follicle telogen with senescence. The former are among the leading theories, along with actual loss of stem or progenitor cells or failure of stem cells to differentiate into progenitors.
 


Edited by Michael, 28 July 2018 - 03:04 AM.


#582 Moondancer

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Posted 28 July 2018 - 03:23 PM

So does anyone know how to go about to place an order as an individual with PepScan (or alternatively: GenScript) for FOXO4-dri? 

 

With the group buy turning out not to be what I assumed it to be when I purchased the peptide, I'd quickly want to place a new order - to get what I was trying to get in the first place.

 

As nearly 7 months have passed since I paid for the peptide, I don't want to wait much longer. (Not in the least since I have a debilitating disease that progressed rapidly the past 3 months, will make me crippled at a younger age, and it was the reason I wanted to try FOXO4-dri 7 months back).

I would be interested in another group buy with preferrably PepScan (given how things turned out with the other group buy), but I feel I have not much time to waste/wait anymore, and I'm not sure how long it would take to set something up.

Thanks.



#583 extendcel

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Posted 28 July 2018 - 04:35 PM

So does anyone know how to go about to place an order as an individual with PepScan (or alternatively: GenScript) for FOXO4-dri?

With the group buy turning out not to be what I assumed it to be when I purchased the peptide, I'd quickly want to place a new order - to get what I was trying to get in the first place.

As nearly 7 months have passed since I paid for the peptide, I don't want to wait much longer. (Not in the least since I have a debilitating disease that progressed rapidly the past 3 months, will make me crippled at a younger age, and it was the reason I wanted to try FOXO4-dri 7 months back).
I would be interested in another group buy with preferrably PepScan (given how things turned out with the other group buy), but I feel I have not much time to waste/wait anymore, and I'm not sure how long it would take to set something up.
Thanks.

You may want to contact them directly for a custom synthesis quote. I do not think much people will want to participate in another group buy after this. Pretty ridiculous behavior from the organizer, but not unusual for a such a behavior when dealing with this quantity of money.

If you are desperate then you could try your hand with the chinese supplier as mentioned before. I've used the same supplier as where the other user ordered his foxo4dri for other peptides, and it was acceptable. They seem to use the same lab as genscript.

Edited by extendcel, 28 July 2018 - 04:38 PM.

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#584 Moondancer

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Posted 28 July 2018 - 06:03 PM

You may want to contact them directly for a custom synthesis quote. I do not think much people will want to participate in another group buy after this. Pretty ridiculous behavior from the organizer, but not unusual for a such a behavior when dealing with this quantity of money.

If you are desperate then you could try your hand with the chinese supplier as mentioned before. I've used the same supplier as where the other user ordered his foxo4dri for other peptides, and it was acceptable. They seem to use the same lab as genscript.

 

Thanks for the info!

I thought PepScan only sells to laboratoriums, not to individual buyers - but perhaps I'm wrong?

 

(When you mention the Chinese supplier: I believe their FOXO4-dri didn't come with guaranteed TFA-removal, and frankly just in general I would feel more comfortable buying from a bit more reputable source).



#585 Andey

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Posted 29 July 2018 - 12:04 PM

Buckylabs sells FOXO4 DRI for prices that are quite comparable to this group buy

20mg for $300

https://www.buckylabs.com/products/

 


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#586 Cerebroo

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Posted 31 July 2018 - 11:01 AM

Can i inject the foxo peptide i bought here with normal bak. water? I do not care about pain, but i care for lasting damage. So is the PBS only for the pain or also against damage of the acid? Thx for help



#587 smithx

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Posted 01 August 2018 - 05:08 AM

No it is not easier, it is exactly the same procedure. While D amino acids may have slightly different biological properties, their chemical functionality is still the same as L amino acids.

Producing retro inverso peptides still uses solid phase synthesis, except you are using D amino acids instead of L. You still use the same protecting group as L amino acids which is usually Fmoc. The main difference is cost, but it doesn't make the synthesis easier or harder.


It's not exactly the same, and if companies haven't done it before, or much of it, they may not get it right. That's the issue.

Also, FOXO4-DRI can be described as a competitive inhibitor of the FOXO4 protein by disrupting FOXO4-p53 interaction. The bound protein complex favors senescence while apoptosis is favored without this interaction. FOXO4-dri is a fragment that can bind to p53 but the complex itself is not active.


Right, that's what I said, but was trying to put it in simpler terms.

Anyway, if you prefer to safe a few thousand dollars taking something that is *probably* correct rather than buying from the actual supplier who made the compound used in the published study, that's up to you, but I'd consider it "penny-wise and pound foolish".
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#588 smithx

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Posted 01 August 2018 - 05:13 AM

So does anyone know how to go about to place an order as an individual with PepScan (or alternatively: GenScript) for FOXO4-dri?


Basically you need two things:

1) a company
2) to know how to order correctly and sound knowledgeable

If you have a company, there's no one to say that it's *not* a research company. If you sound like you know what you're doing, they have no reason not to sell it to you.

Unless you say you're planning to use it on yourself or other people, in which case they will not sell it to you at all, or will require proof that you are conducting an IRB-approved clinical trial.


Edited by smithx, 01 August 2018 - 05:14 AM.

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#589 smithx

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Posted 01 August 2018 - 05:15 AM

Buckylabs sells FOXO4 DRI for prices that are quite comparable to this group buy

20mg for $300

https://www.buckylabs.com/products/

 

How do we know it's really the right compound though?  Or how much TFA is in it. etc.


Edited by smithx, 01 August 2018 - 05:17 AM.


#590 The Capybara

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Posted 01 August 2018 - 05:54 AM

I would never buy from Buckylabs.

Many months ago I had asked them for the actually purity testing on their FOXO4-dri product, and they refused to supply it, as if test results were proprietary.

They did give me a story on how it was pure, but absolutely no data.

If you buy from them and get no results, how do you know it's because the FOXO4-dri didn't work, or whether it was simply not the peptide it claimed to be?

The owner of Buckylabs also posted his first hand experience with the peptide, which was absolutely implausible. I'll leave that up to you to go back and look it up in this thread.


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#591 The Capybara

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Posted 01 August 2018 - 06:05 AM

I've worked on peptide synthesis as part of my grad work.

D forms of amino acids are typically as easy to work with in Fmoc and Boc as L forms, though D forms cost a lot more (at least when I was working with them).

You don't need to find a lab that specializes in D amino acids.

The yields on FOXO4-dri are undoubtedly low, the amino acids are spendy, and so the price to you guys will be high.


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#592 Moondancer

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Posted 02 August 2018 - 04:32 AM

Basically you need two things:

1) a company
2) to know how to order correctly and sound knowledgeable

If you have a company, there's no one to say that it's *not* a research company. If you sound like you know what you're doing, they have no reason not to sell it to you.

Unless you say you're planning to use it on yourself or other people, in which case they will not sell it to you at all, or will require proof that you are conducting an IRB-approved clinical trial.

 

Thanks, that is helpful.

Even if I could order via a company, this is going to be an issue since for many reasons it could be verified in an instance the company is not a research company. Plus: I have no doubt I won't sound knowledgeable.

 

I know the previous group buy turned out to be very problematic, but is there truly no one also considering ordering from PepScan?

I wouldn't be asking if I wouldn't see my health and future irreversibly falling apart currently. And I really wanted to have tried FOXO4-dri from a reputable company. (Even if it won't improve the status of my disease: at least I can't regret later on that I haven't given this a try - which I surely will if I won't try). 


Edited by Moondancer, 02 August 2018 - 05:25 AM.


#593 OP2040

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Posted 09 August 2018 - 11:23 AM

ok, I see we've moved on, but I can't just drop the fact that someone stole almost $1000 from numerous people.  Before I move on, I want my money back at least.  Who is up for pursuing a lawsuit against this guy?  We know his name and where he lives.  Don't get me wrong, we probably don't have a legal case, but at least it is doing something rather than nothing, and it certainly wouldn't be a pleasant experience for our friend.  All I want is my product or my money back. 



#594 recon

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Posted 09 August 2018 - 12:24 PM

Before someone dismisses the idea of a lawsuit, I’d say that it is the best choice. I’d suggest it myself but I have forgotten about it.

OP2040, you should lead the way. Even if you don’t have a case, it’ll be a great experience for everyone considering future actions.

#595 Moondancer

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Posted 09 August 2018 - 12:37 PM

NB: I forgot to mention as I'm overwhelmed by chronic disease, but I heard from Ryan a few weeks back. He said the peptide should be here anytime soon. After everything that happened I'm not sure how reliable that information is however. He still doesn't seem to see any issue in the way he is dealing with this, it was my impression.

Personally I want nothing else but my money back, since this compound from wherever it comes, is not what I agreed on buying: I agreed on buying FOXO-4-dri from GenScript with guaranteed TFA-removal and an agreed on purity level. 

 

I do not see why a lawsuit filed in small claims court would not give us a good chance to retreive our money. And I too would want to partake in that.

Whether a lawsuit would make Ryan reconsider his conduct herein however: I'm not so sure about that. I have kept my mouth shut since I did not want to discredit Ryan posting personal info (let alone about his family), but some family background info looks worrisome up to the extent that I can't help but wonder if the consequences of a lawsuit would bother Ryan at all. He may see it as a minor bump on the road.


Edited by Moondancer, 09 August 2018 - 12:38 PM.


#596 OP2040

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Posted 09 August 2018 - 01:04 PM

I honestly don't think he set out from the beginning to conduct a fraud.  After all, the first group buy seems to have gone well.  My theory is that he got in over his head somehow and either panicked or shrugged it off.  If that is what happened, I am not going to be one to judge, especially since I am trying a group buy myself and it is not going well so far.  However, the part that really bothers me is the lack of communication.  If he just contacted us and dealt with the issue up front, it would be more acceptable.  But I can't accept just disappearing for long periods with no contact.

 

In the meantime, I see some talk of Bucky labs.  I need  to catch up on the thread, but does anyone have any experience with them?  One of the reasons I wanted to try FOX04-dri is because you can basically try it as a one-time thing  decades apart.  So although seemingly expensive, it is actually fairly cheap in the grand scheme of things. 

 

Do we have any more testimonials from people involved in the first group buy?  It's now about 6 months out, so we should be able to determine if there were any lasting effects, good or bad.



#597 Moondancer

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Posted 09 August 2018 - 01:37 PM

So why not finally order from the source that produced FOXO4-DRI for the De Keizer studies, as has been suggested repeatedly by Smithx - and he is absolutely right I find!

Why not ensure that we can be 100% sure we get the right peptide.

 

If we arrange for the group buy differently this time. Their prices are high, but according to Smithx much lower if you order a larger volume of the peptide. I still want to try FOXO4-DRI too - with a chronic disease that will make me disabled if I can't turn the tide, I really want to try this.

 

I know the last group buy did not raise trust in the least, but if we arrange things well this time. First we enquire how long it would take to produce the peptide.

1) Paying to the group buy organiser via Paypal should give 2 months buyer protection, or not?

2) All members taking part in the group buy pay the group buy organiser within 1-2 days so that the order can be placed quickly and buyer protection via Paypal does not expire while waiting for the peptide.

3) the group buy organiser instantly places the order + makes the payment.

4) the group buy organiser shares the document with price quote received from the manufacturer with all the partaking group members via email prior to buying the peptide.

5) the group buy organiser shares the receipt with payment details with everyone taking part in the group buy via email, after completing the payment and receiving the receipt.

6) As soon as the peptide is in, it is shipped to all members.

7) We need to see if this can be reasonably accomplished within Paypal's 2 months of buyer protection. If so, this would give everyone taking part at least some buyer's protection, or not?

 

I for one have been very disturbed about the way this group buy went and thought I would never partake in a group buy again. Yet I am pretty desparate to try FOXO4-dri out, and the prices of the manufacturer that produced the peptide for De Keizer's study are very high, unless a larger volume of the peptide is ordered. I thus for one would be willing to partake again in a group buy - if it is arranged well this time!

I would even go as far as stating that I would be willing to arrange for the group buy if that means I can buy the peptide myself too (since if I buy 100mg the price is sky high around 4700 euro and thus I can not afford the peptide if I buy 100mg on my own. But if we were to order let's say 1gram apparently relatively the price is much lower). But I consider myself unsuitable to organize the group buy since I am a newer member, without decent track record. Plus I would be very worried about shipping the peptide from Europe to the US - afraid it would be seized by customs, and I would be held responsible if it thus wouldn't arrive at the group member's address. I think members would feel safer if a member with a better track record that has been posting here much longer would arrange for this.

 

 

I honestly don't think he set out from the beginning to conduct a fraud.  After all, the first group buy seems to have gone well.  My theory is that he got in over his head somehow and either panicked or shrugged it off.  If that is what happened, I am not going to be one to judge, especially since I am trying a group buy myself and it is not going well so far.  However, the part that really bothers me is the lack of communication.  If he just contacted us and dealt with the issue up front, it would be more acceptable.  But I can't accept just disappearing for long periods with no contact.

 

In the meantime, I see some talk of Bucky labs.  I need  to catch up on the thread, but does anyone have any experience with them?  One of the reasons I wanted to try FOX04-dri is because you can basically try it as a one-time thing  decades apart.  So although seemingly expensive, it is actually fairly cheap in the grand scheme of things. 

 

Do we have any more testimonials from people involved in the first group buy?  It's now about 6 months out, so we should be able to determine if there were any lasting effects, good or bad.

 


Edited by Moondancer, 09 August 2018 - 01:43 PM.


#598 smithx

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Posted 09 August 2018 - 08:46 PM

To chime in here, I did get a quotation from Pepscan last year for 2gm, aliquoted to 10mg vials. They did not specify the production time. Purity was stated to be between 90% and 99% so requiring higher than 90% purity would undoubtedly cost more.

They state:
 

Specified purities refer to UPLC purities obtained with linear gradient system (gradient: 5-55% B in 2 min, flow: 1 ml/min, eluent A: 100 %H2O+0.05% TFA; eluent B: 100% CH3CN+ 0.05% TFA; ) using an C18 RP-HPLC column (i.e. C18, 1,7um, 50x2,1mm) and detection at 215nm.


Cost in USD was about $21,500, so a 90mg purchase (3 treatments of 30mg each) would be about $1K including shipping on to the purchaser.

I am not interested in doing a group buy myself because I'm busy with other projects and also because I feel there is a potential liability risk in case someone uses the compound and has a bad reaction. It would probably make sense for whomever does a group buy to get everyone to sign a release stating that they are taking full responsibility if they use the compound or give it to anyone, and that it is not recommended to do so.

Edited by smithx, 09 August 2018 - 08:48 PM.

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#599 Moondancer

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Posted 09 August 2018 - 10:45 PM

So assuming we were to find a reliable group buy organiser : who would still be interested in a group buy from PepScan?

If we could get the compound for hopefully $1200-$1500 (VAT included) per 100mg (aliquoted per 10mg) from them?

 

Smithx, would you want to partake in such a group buy (not as organiser I understood)?

I for one would want to, if we would have a reliable group buy organiser.

 

Smith, were the prices you mentioned including 21% VAT they charge?

 

Smith makes a good point with regard to liability, and I agree signing a waiver that states the group buy has no liability when it comes to the use of the FOXO4-dri peptide seems like a good idea.


Edited by Moondancer, 09 August 2018 - 10:47 PM.


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#600 smithx

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Posted 10 August 2018 - 12:50 AM

The price quoted was excluding VAT. I'm not sure if VAT would be charged on orders shipped to the USA or not.





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