1569 replies to this topic

[cATsE]

I'm in don't know for how much yet, thanks.

Edited by cATsE, 31 August 2013 - 03:43 PM.

[Hebbeh]

I'm in for at least 2 grams.

[Xenix]

We need to set up a google doc spreadsheet -- like the one that Cyberger made for the second NSI-189 group buy -- to keep track of interested participants.

[Xenix]

I e-mailed the developers of Dihexa (Wright and Harding) a few months ago; I asked about Dihexa's role in neuro-synaptogenesis:

Based on published data with HGF we expect that Dihexa will similarly enhance neurogenesis. We are currently finishing a blind study where we asked that question. We should be unlocking the key in about two weeks. We are also interested in the possible utility of Dihexa in spinal cord injury for exactly the reasons you pointed out. HGF is both a powerful anti-fibrotic agent and a stimulator of neurite outgrowth-exactly what you need for recovery in spinal cord injury. A recent paper in marmosets confirms this in primates. I’ve attached it for your perusal. We believe that Dihexa or other molecules that we have may have utility in any disorder where new neuronal connectivity would be useful including all that you listed. Thanks for your interest

I asked about Dihexa's clinical applications (outside Alzheimer's):

We anticipate that Dihexa and related HGF mimetics may provide a real treatment option for TBI and possibly spinal cord injury. Dihexa is 7 orders of magnitude more powerful than BDNF in inducing new synapse formation, i.e. you get an equivalent response to 10-12M Dihexa and 5X10-6M BDNF and according to the literature HGF far better than BDNF at inducing neurogenesis from neural stem cells. In addition Dihexa can actually get into the brain where BDNF cannot. We are very interested in pursuing TBI applications and in fact recently wrote a grant application to the army that was very well received but didn’t receive funding because we had no preliminary data supporting our ideas.

I asked about specifically where Dihexa is shown to be 7 orders of magnitude stronger at synapse formation than BDNF:

This is all actually published. We compared BDNF to Nle1-AngIV in the Benoist Nov 2011 paper and compared Dihexa to Nle1-AngIV in the McCoy Jan 2013 paper

I asked about its affect on normal, healthy rats:

Good question. With our normal control animals Dihexa does facilitate memory a bit but not nearly as much as in the animal models of AD.

We have discussed the problem (should Dihexa ever make it to market) of students using it to facilitate memory. This would be the equivalent of steroid use in athletes.
...
It clearly does have effects on normal rats. They learn the water maze twice as fast and have better recall, are significantly stronger (after one month of treatment), which is probably due to increased angiogenesis in the muscle, and are noticeably heavier

I also e-mailed Lewis Rumpler (CEO of M3) about the possible issue of glial scarring in stroke victims:

We did a study using the Perforant Path Lesion model and demonstrated reversal of cognitive deficits.
We are highly focused on PD and ALS at this time however.
Stroke would be a great indication but has been resistant to therapeutic intervention.
We think we have a better shot with PD and ALS based on recent data and biology.

[megatron]

I seriously dislike this statement: "We have discussed the problem (should Dihexa ever make it to market) of students using it to facilitate memory. This would be the equivalent of steroid use in athletes."
I think it's safe to say that nearly all of us here at Longecity concur that of all the unfairness of genetics, intelligence is the worst property. A neuroscientist seeing people using a drug to facilitate memory as a problem, absolutely makes me stiff of shock.

On the other hand: How can 1g be enough? Taking 50mg a day like you did Xenix, will only last us 20 days, which can't possibly be anywhere in the neighborhood of how long we need to be taking it to experience anything significant. Lowering the dose will give us a longer span, but will it be enough? Remember the thing about greatly dosage-dependent. Also, I'm not paying $190 a gram, no way. There has to be a more competitive price from a reputable company than that out there.

Edited by Megatrone, 31 August 2013 - 04:35 PM.

[Metagene]

Yeah $190 is too steep.

[Xenix]

I'm not paying $190 a gram, no way. There has to be a more competitive price from a reputable company than that out there.

It is steep, I agree, but this is only based the 50 gram option. If we got a larger order it would significantly cheaper - but I know that the person who would be splitting, weighing, and shipping orders for a WHOLE lot more people would be undergoing a rather enormous hassle - maybe if everyone each contributed an extra percentage of their payment to the person doing this for their time and efforts.

And then there's the large risk involved when something like 27-30 thousand dollars is involved if we were to go with 1KG.

There probably is a cheaper option, but I've dealt with Chinese companies in the past, and my experiences with them haven't be that great. Science Guy's chemist seems very experienced. Those NMR results for NSI-189 were spot on.

[joseph583984]

I'm in for 1 gram.

[Hebbeh]

Most labs will break an order down into pre-packaged smaller sample sizes for a small processing fee. The prices quotes for various order quantities are discounts for scale of manufacturing not scale of packaging.

[Xenix]

Most labs will break an order down into pre-packaged smaller sample sizes for a small processing fee. The prices quotes for various order quantities are discounts for scale of manufacturing not scale of packaging.

Yeah, it's called aliquoting. It can cost around $10 per vial, though. It might get awkward trying to pass 50-100+ vials through customs, though. I think this is the issue Science Guy raised with NSI-189.

[Xenix]

This is the synthesis route that Science Guy's chemist told me:

-((benzyloxy)carbonyl)-L-isoleucine from isoleucine
-make mixed anhydride with isobutyl chloroformate and ((benzyloxy)carbonyl)-L-isoleucine
-make benzyl ((2S,3S)-1-((6-amino-6-oxohexyl)amino)-3-methyl-1-oxopentan-2-yl)carbamate by N-acylation of 6-aminohexanoic acid amide with above mixed anhydride
-deprotect ((2S,3S)-1-((6-amino-6-oxohexyl)amino)-3-methyl-1-oxopentan-2-yl)carbamate with 10% palladium on carbon yielding 6-((2S,3S)-2-amino-3-methylpentanamido)hexanamide

-O-benzylate L-tyrosine cupric chelate in dimethylformamide with benzyl chloride, yielding (S)-4`-benzyloxytyrosine
-N-acylate(S)-4`-benzyloxytyrosine with hexanoyl chloride in tetrahydrofuran with triethylamine as base, yielding (S)-3-(4-(benzyloxy)phenyl)-2-hexanamidopropanoic acid

-combining 6-((2S,3S)-2-amino-3-methylpentanamido)hexanamide and (S)-3-(4-(benzyloxy)phenyl)-2-hexanamidopropanoic acid with carbonyldiimidazole in THF, yielding N-((S)-1-(((S)-1-((6-amino-6-oxohexyl)amino)-4-methyl-1-oxopentan-2-yl)amino)-3-(4-(benzyloxy)phenyl)-1-oxopropan-2-yl)hexanamide
AND hydrogenolysis of the above yielding DIHEXA

Hope he doesn't hate me for posting it.

Someone should approach another custom peptide company and see if they can synthesize it this way. I bet most of them will probably pay no attention and do it their own way -- or worse, say that they will do it that way and choose their own method instead. ESPECIALLY if one was to deal with a Chinese company. Some companies/representatives are terribly arrogant when it comes to telling them how to do their job.

I'd be happy (possibly) paying extra and having the comfort in knowing that it has been synthesized properly, and not cheaply made with impurities, or incorrectly.

[Krabby]

I seriously dislike this statement: "We have discussed the problem (should Dihexa ever make it to market) of students using it to facilitate memory. This would be the equivalent of steroid use in athletes."
I think it's safe to say that nearly all of us here at Longecity concur that of all the unfairness of genetics, intelligence is the worst property. A neuroscientist seeing people using a drug to facilitate memory as a problem, absolutely makes me stiff of shock.

On the other hand: How can 1g be enough? Taking 50mg a day like you did Xenix, will only last us 20 days, which can't possibly be anywhere in the neighborhood of how long we need to be taking it to experience anything significant. Lowering the dose will give us a longer span, but will it be enough? Remember the thing about greatly dosage-dependent. Also, I'm not paying $190 a gram, no way. There has to be a more competitive price from a reputable company than that out there.

What quantity and time period do you feel would be enough in order to get some valid results from this substance?
I would be willing to buy enough in order to do a long term assessment as long as the total quantity does not cost too much.

Edited by Krabby, 31 August 2013 - 06:04 PM.

[hadora]

how can you synthesize a peptide that you don't even know the structure ?

[Hebbeh]

Most labs will break an order down into pre-packaged smaller sample sizes for a small processing fee. The prices quotes for various order quantities are discounts for scale of manufacturing not scale of packaging.

Yeah, it's called aliquoting. It can cost around $10 per vial, though. It might get awkward trying to pass 50-100+ vials through customs, though. I think this is the issue Science Guy raised with NSI-189.

My understanding from the epitalon group buy was they had Genscript aliquot and individually ship samples far cheaper...like a dollar or 2 per sample for aliquoting. Perhaps daouda can weigh in since I know he obtained quotes. And shipping shouldn't be an issue for a lab. It wasn't for Genscript. That is how they do business after all.

[jabowery]

...
Considering how small a dosage is required (2mg/kg in rats orally)...

Whoa!! Is that ug (u=micro) rather than mg (m=milli)?

2mg/kg/day doesn't seem like a small dose of anything.

[Xenix]

...
Considering how small a dosage is required (2mg/kg in rats orally)...

Whoa!! Is that ug (u=micro) rather than mg (m=milli)?

2mg/kg/day doesn't seem like a small dose of anything.

It's milligrams. 2mg/kg is the dosage for rats, extrapolated to a human equivalent dose, it is between 25-40mg.

[jabowery]

...
Considering how small a dosage is required (2mg/kg in rats orally)...

Whoa!! Is that ug (u=micro) rather than mg (m=milli)?

2mg/kg/day doesn't seem like a small dose of anything.

It's milligrams. 2mg/kg is the dosage for rats, extrapolated to a human equivalent dose, it is between 25-40mg.

A lot of well muscled and/or mildly over-weight men are 100kg so the upper end of 40mg/kg/day translates to a mere 0.4mg/kg/day for humans.

Did I miss something?

[megatron]

I seriously dislike this statement: "We have discussed the problem (should Dihexa ever make it to market) of students using it to facilitate memory. This would be the equivalent of steroid use in athletes."
I think it's safe to say that nearly all of us here at Longecity concur that of all the unfairness of genetics, intelligence is the worst property. A neuroscientist seeing people using a drug to facilitate memory as a problem, absolutely makes me stiff of shock.

On the other hand: How can 1g be enough? Taking 50mg a day like you did Xenix, will only last us 20 days, which can't possibly be anywhere in the neighborhood of how long we need to be taking it to experience anything significant. Lowering the dose will give us a longer span, but will it be enough? Remember the thing about greatly dosage-dependent. Also, I'm not paying $190 a gram, no way. There has to be a more competitive price from a reputable company than that out there.

What quantity and time period do you feel would be enough in order to get some valid results from this substance?
I would be willing to buy enough in order to do a long term assessment as long as the total quantity does not cost too much.

When we first do this, we do it right. I say at least two months worth of material. I'm seemingly not very sensitive to anything, so I'm going to operate with a high dose. Ingesting 50mg a day for two months is approx. 3g. For this group buy I'm obtaining 3g as a minimum. I want to go "all in" with the first group buy, so I won't have to reorder due to insufficient amount like in the first group buy of NSI-189. I give this one shot, and one shot only.

Edited by Megatrone, 31 August 2013 - 08:12 PM.

[sparkk51]

I really feel that the 1kg quote is the only doable option as far as price goes, and I don't think we can manage to acquire 27-30k. Even if we could, managing that many people would be way too difficult.

[Absent]

Is there a link to actually buy some of this stuff..? I am interested to try it, and I have money to drop on it. Though you can't synthesize something without knowing the structure.

[Izan]

guys come on, you really think 190 dollars for 1 gram is too steep? this will have permanent positive effects on your cognition, which imho is priceless! let's do this, don't go with shady chinese chem companies. and yes, T&W is really not that good at all. anyways, i'm in for at least 2 grams.

[megatron]

guys come on, you really think 190 dollars for 1 gram is too steep? this will have permanent positive effects on your cognition, which imho is priceless! let's do this, don't go with shady chinese chem companies. and yes, T&W is really not that good at all. anyways, i'm in for at least 2 grams.

We really don't know if it's going to work, and if it does give some positive effects, to what extent?

[megatron]

I would probably accept if we could get the price down to $90/gram. Going from 50g to 100g reduced the price by $50/gram, so it would be awesome if we could get say 150g for $80-$90/gram.

[joseph583984]

I'm in for whatever amount it takes to get into the group buy, up to 3 grams... as long as its verified to be synthesized properly.

Edited by joseph583984, 31 August 2013 - 10:50 PM.

[spookytooth]

I am in, The amount will depend on the price.

[Xenix]

...
Considering how small a dosage is required (2mg/kg in rats orally)...

Whoa!! Is that ug (u=micro) rather than mg (m=milli)?

2mg/kg/day doesn't seem like a small dose of anything.

It's milligrams. 2mg/kg is the dosage for rats, extrapolated to a human equivalent dose, it is between 25-40mg.

A lot of well muscled and/or mildly over-weight men are 100kg so the upper end of 40mg/kg/day translates to a mere 0.4mg/kg/day for humans.

Did I miss something?

No, 40mg/day was roughly what I calculated I would need for my own body weight at 90kg.

[uralsky]

I would like to get in.
Perhaps it will be easier to organize a large group after NSI189 is done. Based on how is going there the majority order similar quantity based on expected length of use and price.
The question is what time is needed to see permanent improvement by raising neurogenesis?

[celebes]

Count me in for a g at least.

[jabowery]

...
Considering how small a dosage is required (2mg/kg in rats orally)...

Whoa!! Is that ug (u=micro) rather than mg (m=milli)?

2mg/kg/day doesn't seem like a small dose of anything.

It's milligrams. 2mg/kg is the dosage for rats, extrapolated to a human equivalent dose, it is between 25-40mg.

A lot of well muscled and/or mildly over-weight men are 100kg so the upper end of 40mg/kg/day translates to a mere 0.4mg/kg/day for humans.

Did I miss something?

No, 40mg/day was roughly what I calculated I would need for my own body weight at 90kg.

But 0.4mg/kg/day is a far cry from 2mg/kg/day. How did you justify lowering the per body weight dosage by a factor of 5 or so for humans from that for rats?

[Absent]

If I had a ton of this stuff and none of you guys had to put money upfront for a group buy, how much would you be willing to pay per gram? Rather, if you could send money and receive it within 3 days, how much would you pay?