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Dihexa: "it would take 10 million times as much BDNF to get as much new synapse formation as Dihexa."


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#211 daouda

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Posted 19 April 2013 - 02:00 AM

You just cannot say "it's all just BS". For example, massages are the best therapy for muscle issues, they're not even used nearly enough in western meddicine, and siddha marma or "thokkanam" (intense full body massages with oils usually done by masters of "kalari" a south india martial art + steam bath etc, for 14 or 21 days) has given great benefits to many fibromyalgics.
Also "success is purely placebo" you cannot say. Among many counter examples, artemisia now is currently the best antimalarial (recognized by western medicine, pharm cies produce a synthetic version now) and comes straight from TCM.
Just because you had a terrible reaction to a TCM medication does not allow you to say "all TCM is BS and success is purely placebo".
I had (still have) terrible brain and body damage from fluoroquinolone antibiotics that didnt even cure my prostatitis and I dont consider all western medicine and pharmaceuticals to be pure BS.

Taking Vytorin reduces your risks of heart attack? http://www.nbcnews.c...w/#.UXClbLXxpGg

Edited by daouda, 19 April 2013 - 02:26 AM.


#212 daouda

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Posted 19 April 2013 - 02:25 AM

in general eastern medicine is primitive, based on old theorys like elemental stuff that western science has long discarded. Like fire is inflammation and so on.

Of course these things have no real material reality, but they are models that form a system, and who cares if they dont represent anything "real" as long as the system somehow works? Western science (and medicine) is continuously updating its knowledge based on new discoveries that render old models/theories obsolete and inaccurate, however therapies based on these flawed models still worked... Like with economy, many economic models are immensely remote from the actual reality that is impossible to apprehend in all its complexity and details, but we still need models to take actions, and well many of the actions based on these models just work. Eastern medicine are empirical systems that are liberated from the obsession to explain the actual material reality down to the most tiniest elements and details, and this leads to different, working therapies that western medicine will never be able to get to because of its obsession with "science". Or so I beleive at least...

Now, how about getting back on topic : DIHEXA!!?

Edited by daouda, 19 April 2013 - 02:28 AM.


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#213 abelard lindsay

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Posted 19 April 2013 - 02:29 AM

guy Dihexa is a HGF agonist..
and it was already tried in rats


So I was reading about HGF agonists, and they increase stem cell growth. They are also what cancers use to metastasise. I'm not saying that in healthy people it would cause problems, but it's something to be aware of.

http://en.wikipedia.org/wiki/C-Met


MET is a membrane receptor that is essential for embryonic development and wound healing. Hepatocyte growth factor (HGF) is the only known ligand of the MET receptor. MET is normally expressed by cells of epithelial origin, while expression of HGF is restricted to cells of mesenchymal origin. Upon HGF stimulation, MET induces several biological responses that collectively give rise to a program known as invasive growth.

Abnormal MET activation in cancer correlates with poor prognosis, where aberrantly active MET triggers tumor growth, formation of new blood vessels (angiogenesis) that supply the tumor with nutrients, and cancer spread to other organs (metastasis).

...

Normally, only stem cells and progenitor cells express MET, which allows these cells to grow invasively in order to generate new tissues in an embryo or regenerate damaged tissues in an adult.


Stem cells grow in response to HGF agonists, which is great, but so do cancer cells. This means that one better not have any weird looking moles for example or cancers in remission as this could stimulate cancer cells. On the positive side, maybe this could regrow hair by activating stem cells on the scalp or repair damage to parts of the body besides the brain?
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#214 Xenix

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Posted 19 April 2013 - 03:12 AM

I asked my supplier for the molecular structure, they sent me this:

Posted Image

What do you think? is accurate?

Edited by Xenix, 19 April 2013 - 04:04 AM.


#215 Xenix

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Posted 19 April 2013 - 04:18 AM

...

I'm very curious to know because when you look up any chemical by its CAS number, you get many different visual representations (molecular structures) and systematic names - which are the same compound, but are represented differently.

My (very limited and undereducated) understanding of molecules/drugs is that they bind onto certain receptors to release certain neurotransmitters...

But if the compound is rearranged so that it contains all of its parts but in a different structural order - say if one were to compare the above structure I was given to those found on page 4 (shared by Erebus and Hadora of this thread) - would it have the same/similar desired effect as real Dihexa? I hope so, or else I've just flushed money down the toilet if my supplier got it wrong.

TL/DR: how close can a custom peptide manufacturer get to the real drug based on its chemical name (N-hexanoic-tyr-ile-(6) hexanoic amide) alone? And do slight variations/rearrangements of chemical structures affect the way that the drug will act?

Edited by Xenix, 19 April 2013 - 04:29 AM.

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#216 Erebus

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Posted 19 April 2013 - 09:46 AM

I asked my supplier for the molecular structure, they sent me this:

Posted Image

What do you think? is accurate?



Looks just about right to me. It's basically identical to the second structure posted on page 4.

The way a molecule is drawn on a two-dimensional plane often has very little to do with its three-dimensional configuration. XRD is the best way to get a three-dimensional image, but even that has its limitations... For one thing, it would generally be a static image, whereas we shouldn't expect dihexa to be an entirely static molecule...

Ah, long story short, I think that the image they showed you should indeed be "Dihexa". Whether or not they managed to actually make it is another matter entirely. The only way to find out would be to submit a small sample for analysis via mass spec.
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#217 Xenix

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Posted 19 April 2013 - 09:59 AM

I asked my supplier for the molecular structure, they sent me this:

Posted Image

What do you think? is accurate?



Looks just about right to me. It's basically identical to the second structure posted on page 4.

The way a molecule is drawn on a two-dimensional plane often has very little to do with its three-dimensional configuration. XRD is the best way to get a three-dimensional image, but even that has its limitations... For one thing, it would generally be a static image, whereas we shouldn't expect dihexa to be an entirely static molecule...

Ah, long story short, I think that the image they showed you should indeed be "Dihexa". Whether or not they managed to actually make it is another matter entirely. The only way to find out would be to submit a small sample for analysis via mass spec.


Ok, good to know. So the systematic name by itself should be enough? hypothetically, if I had the actual molecular structure of Dihexa, and I were to ask for a synthesis, would I have a better chance of getting REAL Dihexa than just the systematic name?

When my batch of Dihexa finally arrives (I was quoted at 2-3 weeks, it has now been over 5 weeks) it will come with a HPLC and mass spec analysis.

If I post these documents here, will you be able to tell whether or not it is Dihexa, or do you have to perform these tests yourself? please excuse my nooby ignorance lol. I am still willing to send you a 10mg sample to test, but if it is unnecessary then I'd rather not mess around with trying to get it past customs.

#218 hadora

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Posted 19 April 2013 - 10:07 AM

Xenix don't forget that dihexa should be stored at -20° celsius
plus why did you order it from china, there plently of euro and american company that do custom peptide plus there is a member here that do peptide synthesis i think, you can ask him if he can do that for you

Edited by hadora, 19 April 2013 - 10:09 AM.


#219 Erebus

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Posted 19 April 2013 - 10:16 AM

I asked my supplier for the molecular structure, they sent me this:

Posted Image

What do you think? is accurate?



Looks just about right to me. It's basically identical to the second structure posted on page 4.

The way a molecule is drawn on a two-dimensional plane often has very little to do with its three-dimensional configuration. XRD is the best way to get a three-dimensional image, but even that has its limitations... For one thing, it would generally be a static image, whereas we shouldn't expect dihexa to be an entirely static molecule...

Ah, long story short, I think that the image they showed you should indeed be "Dihexa". Whether or not they managed to actually make it is another matter entirely. The only way to find out would be to submit a small sample for analysis via mass spec.


Ok, good to know. So the systematic name by itself should be enough? hypothetically, if I had the actual molecular structure of Dihexa, and I were to ask for a synthesis, would I have a better chance of getting REAL Dihexa than just the systematic name?

When my batch of Dihexa finally arrives (I was quoted at 2-3 weeks, it has now been over 5 weeks) it will come with a HPLC and mass spec analysis.

If I post these documents here, will you be able to tell whether or not it is Dihexa, or do you have to perform these tests yourself? please excuse my nooby ignorance lol. I am still willing to send you a 10mg sample to test, but if it is unnecessary then I'd rather not mess around with trying to get it past customs.



-Yes, the systematic name by itself should be enough... but, very generally, the more information you can give 'em, the better it'll go for you.

-HPLC and mass spec results (presumably from an LC/MS run) should be more than enough to determine approximate purity and identity. But I would never, ever trust documentation from a supplier without verifying it independently. Chromadex, Sigma, and many Universities offer analytical services. (I don't like smaller outfits like RTP Labs, so I wouldn't recommend them.)
I can also analyze it for you here via ESI/MS or MALDI-TOF/MS... Customs shouldn't be a problem to HK...

#220 Xenix

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Posted 19 April 2013 - 10:19 AM


What do you think? is accurate?



Looks just about right to me. It's basically identical to the second structure posted on page 4.

The way a molecule is drawn on a two-dimensional plane often has very little to do with its three-dimensional configuration. XRD is the best way to get a three-dimensional image, but even that has its limitations... For one thing, it would generally be a static image, whereas we shouldn't expect dihexa to be an entirely static molecule...

Ah, long story short, I think that the image they showed you should indeed be "Dihexa". Whether or not they managed to actually make it is another matter entirely. The only way to find out would be to submit a small sample for analysis via mass spec.


Ok, good to know. So the systematic name by itself should be enough? hypothetically, if I had the actual molecular structure of Dihexa, and I were to ask for a synthesis, would I have a better chance of getting REAL Dihexa than just the systematic name?

When my batch of Dihexa finally arrives (I was quoted at 2-3 weeks, it has now been over 5 weeks) it will come with a HPLC and mass spec analysis.

If I post these documents here, will you be able to tell whether or not it is Dihexa, or do you have to perform these tests yourself? please excuse my nooby ignorance lol. I am still willing to send you a 10mg sample to test, but if it is unnecessary then I'd rather not mess around with trying to get it past customs.



-Yes, the systematic name by itself should be enough... but, very generally, the more information you can give 'em, the better it'll go for you.

-HPLC and mass spec results (presumably from an LC/MS run) should be more than enough to determine approximate purity and identity. But I would never, ever trust documentation from a supplier without verifying it independently. Chromadex, Sigma, and many Universities offer analytical services. (I don't like smaller outfits like RTP Labs, so I wouldn't recommend them.)
I can also analyze it for you here via ESI/MS or MALDI-TOF/MS... Customs shouldn't be a problem to HK...


Ok, you've convinced me. I will contact you via PM and send a sample as soon as it arrives. Hold tight.

Edited by Xenix, 19 April 2013 - 10:20 AM.


#221 Xenix

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Posted 19 April 2013 - 07:06 PM

OK, I've just got some (long overdue) news from another supplier I contacted for a quote over a month ago; I asked him if he could synthesise Dihexa in acetate salt format, here's what he replied with:

To your questions. Firstly the product cannot chemically be an acetate salt as there is no charged species in the structure that can be protonated and therefore require an acetate counter ion. So the quotation you received from the other supplier stating that the product would be supplied as an acetate salt cannot be correct.


I'm confused - all of the other suppliers have told me that they were able to synthesise it in acetate salt format (as I requested) by transforming it from TFA into acetate salt using an acetate buffer; should I have asked for it in free amine salt format instead?

#222 daouda

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Posted 19 April 2013 - 07:44 PM

Maybe you shoudln't be so secretive about these suppliers (there's no need for it, look at the other group buys going on, everything is out in the open), so that those familiar with these kind of things here could tell you wether they look reliable or not?

#223 Xenix

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Posted 24 April 2013 - 04:22 AM

As promised


Posted Image

Posted Image

Posted Image

#224 Erebus

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Posted 24 April 2013 - 04:55 AM

There's no hint of an acetate-anything. The MW is roughly 504.5 -- as you'd expect from the image they posted earlier in the page -- so [M+H]+ is roughly 505.5 and the sodium adduct, [M+Na]+, is 527.5.
What I'm finding strange is that the lower-boundary of their range is 299, and that they haven't shown you any fragmentation. You can't verify a structure without fragmentation; a molecule's fragmentation profile is its fingerprint. Your MS results could practically belong to any stable compound with an MW of 504.5. (There are exceptions, of course. We know that it doesn't contain Cl or Br, for example, due to the lack of isotope peaks.)

...I'd say that further testing is warranted.

#225 Erebus

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Posted 24 April 2013 - 05:03 AM

Do you have a better-resolution MS image? I can check the height of the carbon-13 peak -- which would be at 506.5, hence the need for a high resolution -- and estimate (quite roughly) how many carbon atoms your structure contains.

#226 therein

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Posted 24 April 2013 - 06:16 PM

It's been a while since I last checked this thread. Can someone fill me up on the group buy? Is it happening?

#227 megatron

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Posted 24 April 2013 - 09:05 PM

Anyone have any more articles on Dihexa?

#228 therein

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Posted 24 April 2013 - 09:24 PM

I have access to full-text versions of PubMed, Elsevier and ScienceDirect articles. Let me know if only have the abstracts but want to see the full-text.
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#229 Passion

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Posted 25 April 2013 - 06:17 AM

I'm definitely interested in a group buy for this if there's still room.

#230 HappyPhysicist

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Posted 25 April 2013 - 02:20 PM

Count me in on a group buy, although unless its being organized via PM it doesn't seem to be happening.

This sounds pretty interesting for me (I'm the guy with ALS). If it can help motor neurons to regenerate to some extent then I should be able to notice it pretty quickly. One proposed cause of ALS is a defect in the ANG gene which leads to a lack of vascularization in the vicinity of dying motor neurons which creates a domino effect.

Thanks

#231 Xenix

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Posted 25 April 2013 - 02:31 PM

Count me in on a group buy, although unless its being organized via PM it doesn't seem to be happening.

This sounds pretty interesting for me (I'm the guy with ALS). If it can help motor neurons to regenerate to some extent then I should be able to notice it pretty quickly. One proposed cause of ALS is a defect in the ANG gene which leads to a lack of vascularization in the vicinity of dying motor neurons which creates a domino effect.

Thanks


There's no group buy at the moment. I'm in the process of having my peptide analysed to check if what I have received is actually what Dihexa should be. If all goes well we could organise a group buy.

#232 HappyPhysicist

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Posted 25 April 2013 - 02:36 PM

Trying to get a quote and this is the info I need:


Peptide_Name:

Peptide_Sequence (from N-terminal to C-terminal):



Modification:

N-terminus (Free amine/other, please specify):

C-terminus (Free acid/Amide/other, please specify):



Peptide_Purity (Crude/Desalted/75%/85%/90%/95%/98%):

Peptide_Quantity (mg):



#233 HappyPhysicist

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Posted 25 April 2013 - 02:48 PM

There's no group buy at the moment. I'm in the process of having my peptide analysed to check if what I have received is actually what Dihexa should be. If all goes well we could organise a group buy.


Thanks. What is your timeline? I would like to try this ASAP as I have only a few months to live (not too concerned about cancer).

Since my diagnosis I have had only two treatments impact my progression. One was sodium chlorite, which dramatically improved my swallowing and speech, but lasted for only about 4 months and the other was an Adipose Derived Stem Cell treatment which improved seemed to be reversing my condition (I was getting stronger) but lasted only a week.

I mention this only to point out that with ALS it seems that for a good deal of time the motor neurons go through a stage of weakness due to the (so far unidentified) assault on them and when this assault is ameliorated the motor neurons that are still alive seem to bounce back quickly.

The physician who performed my stem cell treatment is moving on to gene therapy. His hope is that he has identified the neurotropic substances produced by stem cells and plans to reprogram the motor neurons to produce those substances themselves. I just need to buy some time to see if it works for the first human volunteer and then try it myself and dihexa seems like it could potentially do that.
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#234 Googoltarian

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Posted 25 April 2013 - 03:34 PM

Dihexa is a chiral molecule, but what was drawn by Xenix supplier is a racemic form - and active form is most likely only one enantiomer, which one I will check at work where I have access to chemistry databases.

Also this LC/MS chromatogram is partially bad science, person who done this used C18 column which is the most popular reversed phase column - but for this compound, column with CHIRAL PACKING should be used, then this analysis could show which one of more than 8 possible isomers is made by that supplier.
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#235 Erebus

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Posted 25 April 2013 - 03:45 PM

Dihexa is a chiral molecule, but what was drawn by Xenix supplier is a racemic form - and active form is most likely only one enantiomer, which one I will check at work where I have access to chemistry databases.

Also this LC/MS chromatogram is partially bad science, person who done this used C18 column which is the most popular reversed phase column - but for this compound, column with CHIRAL PACKING should be used, then this analysis could show which one of more than 8 possible isomers is made by that supplier.



Do you know anything about the compound? Have you read the study from the inventors of Dihexa? If so, you'd know that...

A) They themselves used a simple C18 column for separation. (A Rainin Econosphere ODS C18 at 40°C, to be precise).

B) If there's an active enantiomer, they themselves -- the inventors of the compound -- don't even know what it is. They just synthesized the peptide using FMOC chemistry, and they didn't give a damn to check chirality.
...Therefore, nobody has any idea what the 'active' form would look like, and sorting out isomers would be an exercise in futility.

The LC/MS chromatogram sucks, but not for the reasons you've mentioned. It sucks because there's no fragmentation for us to look at, and because the 13C peak looks strange as hell.
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#236 Xenix

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Posted 25 April 2013 - 04:03 PM

There's no group buy at the moment. I'm in the process of having my peptide analysed to check if what I have received is actually what Dihexa should be. If all goes well we could organise a group buy.


Thanks. What is your timeline? I would like to try this ASAP as I have only a few months to live (not too concerned about cancer).

Since my diagnosis I have had only two treatments impact my progression. One was sodium chlorite, which dramatically improved my swallowing and speech, but lasted for only about 4 months and the other was an Adipose Derived Stem Cell treatment which improved seemed to be reversing my condition (I was getting stronger) but lasted only a week.

I mention this only to point out that with ALS it seems that for a good deal of time the motor neurons go through a stage of weakness due to the (so far unidentified) assault on them and when this assault is ameliorated the motor neurons that are still alive seem to bounce back quickly.

The physician who performed my stem cell treatment is moving on to gene therapy. His hope is that he has identified the neurotropic substances produced by stem cells and plans to reprogram the motor neurons to produce those substances themselves. I just need to buy some time to see if it works for the first human volunteer and then try it myself and dihexa seems like it could potentially do that.


I'm very sorry to hear about your condition. I hope it improves. I'm hoping to have the results from the analysis back by early next month. They will be posted on here as soon as they arrive.

#237 Rior

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Posted 29 April 2013 - 07:30 PM

So, uh, Nootly still alive? As far as I know right now, he seems to have been the only one to try Dihexa. He's said it's better than Cerebrolysin. That said, Nootly, if you're still even looking at these forums, have you noticed any major differences? Would love an update here.

#238 daouda

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Posted 29 April 2013 - 08:43 PM

Has anybody tried to get a quote for dihexa from genscript?

#239 Nero

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Posted 29 April 2013 - 09:54 PM

Who's nootly?

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#240 daouda

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Posted 29 April 2013 - 10:03 PM

Who's nootly?

Upper right corner of this page, is a "search" box. Type "nootly"....
But hey, again, I'm a helpful guy http://www.longecity...serMode=content




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