413 replies to this topic

[Rocket]

Omg subq is so easy! Stupid people do it for that stupid hcg diet. IV is what you should fear.

[OP2040]

I will do subQ no problem. My mom is diabetic I know all about it. But there’s a hierarchy and popping a pill is still way better. Having said that, if pills can’t be conclusively proven effective I’d def do SubQ. IV would have to be miracle cure for everything for me to do it at home lol.

[roscotx]

Do you have me in this group buy ?

Roscotx

[Daniel Cooper]

Omg subq is so easy! Stupid people do it for that stupid hcg diet. IV is what you should fear.

 

Well, the only issue with subQ is getting a reasonably sterile solution.  Usually running it through a fine filter is good enough, but you don't want to get sloppy.

 

If it's orally available that's my first choice.

[OP2040]

See this is what I don't like about subQ, and it may just be the way this community is portraying it.  I highly doubt serious infections are that common since like I said I've been watching my mom do it for 30 years.  But the way people talk about it here is that we have to be super-vigilant about it.  I'm not sure if something different about these substances than insulin, maybe the fact that they are lab produced and not sold for human use.   Either way, it's a huge pain in the arse worrying about whether or not I should get a micron filter, or use PBS as with the FOX04-dri.  Also, from that thread, I'm not sure how serious the people are with their reports of "soreness" at the injection site.  We all get "soreness" at the injection site when we get blood drawn for example, I certainly wouldn't include that as a side effect worthy of even mentioning.

 

Anyway, I'm extremely excited about this group buy, I hope we can keep the momentum going.  I have yet to see a non-meatsauce group buy get done, so I'm kinda softening my stance on him. 

 

I'm pretty sure we have enough people now, so what next?  Lets get some quotes and determine best route of admin. 

 

After reading the main study, one thing that stood out for me is that the single dose did just as well or better than the chronic dosing.  This is crazy to me, and it does seem more like a switch is being turned off or on than continuous manipulation.  I wish they had kept the study going a bit longer, but for mice it was plenty long enough, and the one dose deal seems real.  My only other reservation is the litany of "mice models" being used, which I don't trust at all!  But the evidence for this drug is pretty wide across studies and disease states, so I can overlook that.

 

 

[Daniel Cooper]

The difference between what we're talking about and what your mom was doing is that insulin comes in nice pre-packaged vials of sterile solution.

 

If we go subQ we'd be starting with trodusquemine powder from some lab that is not sterile.  It won't be teeming with bacteria, but it definitely won't be sterile.  Then we'd have to turn that into some sort of solution with normal salient or maybe bacteriostatic water.  The end result will not be sterile.  You can pass it through a submicron filter and you'll get most of the bacteria out. If any viruses are present (not terribly likely) your filter may not stop those.

 

I don't want to over blow this.  It will very likely be safe, but it's not like getting something in a nice guaranteed to be sterile vial.

 

 

 

[OP2040]

Thanks David, I figured as much, but it definitely makes subQ somewhat a pain.  Just dealing with the tiny vials that the FOX04-dri came in is going to be annoying.

[OP2040]

Wow, it just keeps getting better.  This is from 2015, but sure could use this affect as well.

 

https://www.scienced...50305125644.htm

 

 

Their new research, together with a previous study, shows that an enzyme called PTP1B plays a crucial role in a molecular pathway that links LMO4, anxiety, obesity and the body's natural marijuana (endocannabinoid) system. When the researchers used a drug, trodusquemine, that specifically inhibits the activity of PTP1B, they found that both anxiety and obesity were reduced.

 

 

 

[CHanderson]

Count me In.

[OP2040]

Lets get into the dosing and pricing.  I'm not sure what the dose should be, but a quick search gets me this price list:

 

600/mg

1140/5mg

1920/10mg

6000/50mg

 

A few things to note.  There doesn't seem to be many sellers, unlike some of the other group buys.  While it does look expensive as usual, I have no idea how price breaks will effect this.

 

The good news is that it can be a one time treatment, making anything under$1000 possible, though still very painful for most.  Anybody want to run some HED numbers based on the following mess?

 

 

The PTP1B inhibitor Trodusquemine was obtained from Dr N Tonks. After 1 week HFD, 20 mice were injected intraperitoneally (I.P.) with the PTP1B inhibitor Trodusquemine (10mg/kg), followed
by 4 subsequent weekly injections at 5mg/kg, as previously described for ob/ob mice [19] and a 6 week washout period. These were designated the chronic group, whereas the remaining mice were injected with saline. After 8 weeks HFD, a further 20 mice were injected with a single dose of 10mg/kg Trodusquemine and designated accordingly, followed by a 4 week washout period. At week 12 of HFD, mice were fasted for 5h and injected with either saline or insulin (10 mU/g body weight) for 10 6 mins prior to culling by CO2 inhalation and subsequent cervical dislocation. Trodusquemine treatment was halted prior to the end of the study to ensure that the procedure of treatment (by intraperitoneal injection) did not affect the terminal signalling experiment by altering stress hormone levels and thus adversely affecting insulin signalling. Heart and aortic tissues were harvested and collected for further analysis. Tissues for subsequent western blot or qPCR analysis were frozen in liquid nitrogen and stored at -80°C until needed, whereas tissues for histology were immersed in formalin for 24h at 4°C, then stored at 4°C in PBS until analysed..

 

 

[Daniel Cooper]

You can't afford it at those prices.  I'm guessing that those numbers came from a mainstream research chemical supplier like Sigma Aldrich or someone similar.  These are the type of suppliers that a University or industry research lab would use.  If you do a one time injection to replicate that mouse experiment you're going to need something like 60 ~ 70mg ( 10(mg/kg)/12.3 * 70(kg) ) .  That's more than $6k according to your price list.

 

You want a synthesis lab, probably in China, to make this for you.  

 

 

[mikey]

You can't afford it at those prices.  I'm guessing that those numbers came from a mainstream research chemical supplier like Sigma Aldrich or someone similar.  These are the type of suppliers that a University or industry research lab would use.  If you do a one time injection to replicate that mouse experiment you're going to need something like 60 ~ 70mg ( 10(mg/kg)/12.3 * 70(kg) ) .  That's more than $6k according to your price list.

 

You want a synthesis lab, probably in China, to make this for you.  

 

 

I wonder which lab provided those seemingly high quotes. Please tell us which lab. All such things should be transparently disclosed.

 

There are many labs that can synthesize it in the US and if in China or if a small lab, we must figure in the cost of testing.

 

My next post goes into figuring dosing for one my weight. 

[smithx]

This compound seems too expensive for most people to use, and I'm not sure of the benefits. From my reading (skimming really) of the main cited study, it appeared that administration of it could reduce the amount of plaque formation, but I didn't find anything about it "melting away" existing plaque. Could anyone paste that citation and the text that states that this compound has any effect on existing arterial plaque?

 

BTW, here are two suppliers I found:

https://www.medcheme...m/MSI-1436.html
http://www.probechem...s_MSI-1436.aspx

 

The first one has the same pricing quoted above. The second one is less expensive but still very expensive.

[CHanderson]

I believe that the "one treatment wonders" is simply because trodusquemine has a very long half-life (atleast a week). 

I am mostly curious about it because of its possible regenerative capacities. I am not a skilled chemist, but as dr. strange said in:    trodusquemine is not that difficult to synthesise. I think that it should be possible to find a supplier or a chemist that will do it for a good price. 

[granmasutensil]

Not interested in joining the group buy. But as far as administration, wouldn't another option be just using a 0.25mm dermaroller people normally already use for penetration of skincare products and just dissolve the compound in some DMSO and slap it on patch of skin you dermarolled? Then maybe stick one of those silicone scar patches ontop and secure with a bandage to just ensure maximum skin contact/absorption. I've seen the patches on the owndoc website in all different sizes, rollers too. Just a thought.

 

Also if it is so effective with one dose, and period of dosage is severely limited why not just suck it up and do multiple lower dose subQ injections instead of one big one?

 

 

[OP2040]

It was the medchemexpress website, literally the first one that shows up in a google search.

https://www.medcheme...m/MSI-1436.html

 

It really is a downer that we have so many great targets now, but we are priced out of almost all of them.  The process can't be inherently expensive if some companies can sell for so much cheaper.  It has to be an economy of scales thing, since labs only sell smaller quantities to begin with.

 

Daniel, do you have a link to one of those cheap Chinese companies that we can request synthesis from? 

 

smithx,  yes the media uses the term "melt away", which is an exaggeration.  But having read the study in this case, it is not much of an exaggeration.  It does show actually reversal of plaques, which is a pretty big deal.  I'm more concerned with the fact that they show it in "model mice" and I'd like to see it in humans, though they do use several models. 

[Daniel Cooper]

It was the medchemexpress website, literally the first one that shows up in a google search.

https://www.medcheme...m/MSI-1436.html

 

It really is a downer that we have so many great targets now, but we are priced out of almost all of them.  The process can't be inherently expensive if some companies can sell for so much cheaper.  It has to be an economy of scales thing, since labs only sell smaller quantities to begin with.

 

Daniel, do you have a link to one of those cheap Chinese companies that we can request synthesis from? 

 

smithx,  yes the media uses the term "melt away", which is an exaggeration.  But having read the study in this case, it is not much of an exaggeration.  It does show actually reversal of plaques, which is a pretty big deal.  I'm more concerned with the fact that they show it in "model mice" and I'd like to see it in humans, though they do use several models. 

 

I'll let Mikey speak to what labs he's looking at.  You can find all sorts of synthesis labs in China (the US as well) that will make things to order.  The trick is vetting them and testing their output.

 

The suppliers that you found are working on a different business model.  They are selling small quantities at high markup to research labs, in other words people with deep pockets.  You can find commercial suppliers that will beat them on cost.  I believe Mikey has experience in the supplement market so he certainly has better contacts than I.

 

 

 

[smithx]

smithx,  yes the media uses the term "melt away", which is an exaggeration.  But having read the study in this case, it is not much of an exaggeration.  It does show actually reversal of plaques, which is a pretty big deal.  I'm more concerned with the fact that they show it in "model mice" and I'd like to see it in humans, though they do use several models. 

 

I read the study too and didn't see where any significant plaque reversal was found. Could you reference and quote that section please?
 

[Daniel Cooper]

I read the study too and didn't see where any significant plaque reversal was found. Could you reference and quote that section please?
 

 

Section 3.2 and figures 5 C&D.

Attached Files

•  Pharmacological inhibition of protein tyrosine phosphatase 1B (PTP1B) protects against atherosclerotic plaque formation in the LDLR mouse model of atherosclerosis.pdf   524.79KB   10 downloads

[smithx]

Thanks, they do show plaque reduction but oddly a single dose worked much better than chronic dosing, which possibly indicates a problem with their protocol or randomness in their results.

 

One thing I found potentially worrisome is the 20% body fat mass loss in a few weeks. It could be beneficial or could indicate some metabolic problem the PTP1B inhibition is causing.

 

Although PTP1B inhibition is being trialed as a cancer treatment, there are indications that inhibiting it could actually cause or worsen other cancers.

https://www.ncbi.nlm...les/PMC3662559/

http://cancerres.aac...ent/65/21/10088

 

 

 

 

[OP2040]

Section 3.2 and figures 5 C&D.

 

This is where I saw it too.  I think the problem is that the figures are not on one version of the study, maybe because it is very new and in manuscript format.  Nevertheless, it should also be in the literature itself, but much harder to see than those nice pics and graphs of receding plaque.

 

It's crazy there are now numerous substances shown to reverse plaque in mice, and most likely translatable to humans.  Off the top of my head Cyclodextrin, Trehalose and this one.  Considering that this is still the #1 killer of people, the medical institutions are completely irresponsible and negligent when it comes to actually trying to cure disease. 

[Daniel Cooper]

Thanks, they do show plaque reduction but oddly a single dose worked much better than chronic dosing, which possibly indicates a problem with their protocol or randomness in their results.

 

One thing I found potentially worrisome is the 20% body fat mass loss in a few weeks. It could be beneficial or could indicate some metabolic problem the PTP1B inhibition is causing.

 

Although PTP1B inhibition is being trialed as a cancer treatment, there are indications that inhibiting it could actually cause or worsen other cancers.

https://www.ncbi.nlm...les/PMC3662559/

http://cancerres.aac...ent/65/21/10088

 

 

It's had a handful of human trials (healthy volunteers, obese type 2 diabetics, breast cancer patients) and no one has noted any long term metabolic issues so far.  

 

I can see how PTP1B inhibition might help prevent the formation of arterial plaques, I just have trouble understanding how a single dose of a PTP1B inhibitor would reverse plaques.  I would not be surprised if there is not some other effect at play here.

 

There are other PTP1B inhibitors out there (magnolia bark, some teas, other natural compounds) and I haven't seen anyone reporting a reversal of CAD for those.  I think there are some assumptions in the MOA.

[Daniel Cooper]

This is where I saw it too.  I think the problem is that the figures are not on one version of the study, maybe because it is very new and in manuscript format.  Nevertheless, it should also be in the literature itself, but much harder to see than those nice pics and graphs of receding plaque.

 

It's crazy there are now numerous substances shown to reverse plaque in mice, and most likely translatable to humans.  Off the top of my head Cyclodextrin, Trehalose and this one.  Considering that this is still the #1 killer of people, the medical institutions are completely irresponsible and negligent when it comes to actually trying to cure disease. 

 

In the Western world in general we have a drug approval process that does not serve the patient very well.

 

It's far to expensive and takes far too long.  And, nobody has any incentive to do a lot of investigation of natural compounds due to the difficulty in obtaining a useful patent.  That used to be a realm that at least the universities had an interest in, but now they too are off chasing the next patentable billion dollar drug.

 

And we have the regulatory agencies that never seem to factor in the patients that will die when they keep a useful drug off the market needlessly for a decade or so into their risk/benefit analysis.

 

The only one this process does serve is the large established pharmaceutical companies where these regulatory bodies effectively keep disruptive technologies at bay.  Wouldn't want to ruin a $11B market for marginally effective statins by someone dropping a trehalose or heaven forbid a one shot treatment like trodusquemine on them.  Also, since it takes roughly a billion dollars US to get a drug through our FDA if you are a small startup that has a better idea, at some point you're going to have to partner or be purchased by one of the established players.  These startups are in a far weaker negotiating position before they have FDA approval than after.

[OP2040]

Daniel,

Absolutely agree on the messed up system we are dealing with.  I think even this system will deliver eventually, but time is obviously very important in this area.  I always look up the natural compounds that are actionable as well, and you mention a few.  There are many of them in this case, and there are quite a few studies.  But you just said yourself why they will never be pursued formally,  Nevertheless, due to the problems of expense and access, I often end up choosing one of these herbal compounds rather than a designed and refined drug.  Bioavailability becomes a major issue with unprocessed compounds.  But there is no doubt in my mind that some of them probably do work fairly well.  In the case of natural PTP1B inhibitors, there are so many of them that I'm still having a hard time sifting through all of them to find the best one.

 

On another note, I'm not even convinced of the etiology atherosclerosis and CD as it is currently understood.  We all believed at one point that basic cholesterol was "bad".  Then it quite rightly moved on to just LDL cholesterol, then oxidized LDL cholesterol, then macrophages and foam cells got into the act.  Sounds as if we are getting closer to the truth.  Based on that progression, and that of alzheimer's and even cancer, it seems like the immunosenescence has a much bigger role to play in all age-related disease than we give it credit for.  I'd love to see the effect of a youthful, rebooted immune system on all these diseases,  A lot of the interventions that work can be characterized as lessening the burden on the immune system, or targeting it indirectly in some way.  One of the other things that can reverse arterial plaque is macrophage polarization to M2.  It's been demonstrated at least twice now that this is the main mechanism of action in cases of plaque reversal.  And implicated in a number of other diseases, as well as in the regeneration of regenerative animals.  But I digress.....

[Zxone]

Mikey: Please include me in the two buys.
Many thanks,
Zxone

[mikey]

Mikey: Please include me in the two buys.
Many thanks,
Zxone

 

 

You're included. However, this is only for buying Trodusquemine.

Here's the list of 18 +1 of my friends. If I am missing anyone please alert me. (I have one friend that confirmed to me personally.)

 

Group Buyers                 Level of Interest

1

Beetlejuice

interested

 

 

2

Orinoco

Depending on price and who orders it

 

 

3

The Capybara

might jump in to this one.

 

 

4

Death2aging

I’m in

 

 

5

Ceridwen

Yes, interested

 

 

6

Acetylnordopatoninol

Would also join

 

 

7

Daniel Cooper

Depending on source and how administered

 

 

8

SumWon

Interested

 

 

9

thedarkbobo

Interested if oral and not super-hi priced

 

 

10

Mikey

Interested and working on it

 

 

11

classicstrat

Interested provided it is affordable

 

 

12

docmaas

I’m interested

 

 

13

Robert

 

 

 

14

Bzork

Interested in GB

 

 

15

roscotx

In as well

 

 

16

bladedmind

in

 

 

17

CHanderson

Count me in

 

 

18

Xzone

Include in 2 buys?

 

 

[Vermonter]

Hello Everyone,

 

I just subscribed to longecity, just for this group buy. There are a couple of other aminosterols that may have most of same benefits that might be more available/cheaper to manufacture (squalamine, claramine). MSI-1436 / Trodusquemine would be best, however.

 

In other words, I am in.

[Vermonter]

https://www.ncbi.nlm...pubmed/25623533

 

Functional properties of Claramine: a novel PTP1B inhibitor and insulin-mimetic compound.

[OP2040]

Add me to the list, depending on price

[mikey]

We now have 20 interested people in our group buy.

 

I sent out 10 queries for price quotes about an hour ago, being optimistic and hoping that the price would be significantly less than manufacturers provide on their sites.

 

Note that the vendors that had pricing listed on their sites were all about the same for small doses of from 1 mg ($600) to 50 mg ($6,000).

Size Price Stock 1 mg USD 600   5 mg USD 1140   10 mg USD 1920   50 mg USD 6000

Ah. I just received an email quote from GLIX. (I will supply the list of companies that I asked for quotes if anyone wants it.)

GLIX sent this quick quote: "We can offer you $10,000/g if you order 200g, expecting to deliver in 24 weeks."

I guess that we are too far ahead of market demand, so pricing is outrageous and I don't expect the other vendor quotes to be much, if any better. 

My computation of what I would need IV as one two-hour IV-drip that is based on HED data from mice to humans and then looking at the terminated human breast cancer study is 0.757 grams.

This means that I would have to spend something like $7,570 for my single IV-drip dose. Would I spend it? Yes, if it was as effective at regenerating human arteries as it did for mice it would be worth it to me. This, of course, is still a bit of a gamble.

 

To provide background I provide the following.

 

The patent has some wide-ranged dosing considerations for IV, subq, nasal, topical, oral and rectal administration.

Section 8 has the following: Note the patent's stated doses equal less than the dose-effectiveness study on mice for atherosclerosis.

 

Let us also note that a patent is going to give round high and low numbers so that they can enforce their patent if anyone comes up with a formula to be used with this ingredient at basically any potentially effective amount.

So, we might consider that the breast cancer numbers are more likely where we are to devise our human oral and subq dosing.

 

From the patent:

 

The following dosage ranges are exemplary. Suitable dosages for intravenous administration are generally about 20 micrograms to 40 milligrams of active compound per kilogram body weight.

 

Suitable dosage ranges for intranasal administration are generally about 0.01 mg/kg body weight to 1 mg/kg body weight.

Suitable dosage ranges for topical administration are generally at least about 0.01% by weight. 

Suitable dosages for oral administration are generally about 500 micrograms to 800 milligrams per kilogram body weight, and preferably about 1-200 mg/kg body weight. 

Suppositories generally contain, as the active ingredient, 0.5 to 10% by weight of the aminosterol active ingredient. Oral formulations preferably contain 10% to 95% active ingredient.
----------------------------------------------------------------------------------------

When I calculated the HED from mice to me at 200 lbs (~90 kg) I got about 757 mg.

 

Note that the patent states oral doses as being about 20-25 times greater than IV, which makes a hope for oral administration basically impossible unless a person has a lot of money.

 

Because the concept of cost is now quite serious I would definitely go the extra route of acquiring the IV-drip equipment and having a medically adept friend administer this to me.

 

That is my report. Please let’s hash this out, folks. I think it wiser to continue considering it, but we know that we would have to be quite convinced that it was worth the money and trouble - meaning that, because of cost, administration basically would have to be a two-hour IV-drip.

 

This was a lot of work. I’m glad the hard part is basically over. Perhaps my calculations have some missteps and can be tightened up a bit.

However, we can be sure that the administration of an effective dose of TD would be perhaps the most costly “buy” that ever occurred via LongeCity’s forums IF it occurs.

 

I ask for your thoughts. 

 

Edited by mikey, 22 September 2018 - 05:42 AM.