413 replies to this topic

[mikey]

"Researchers from the University of Aberdeen claim that just a single dose of the new drug Trodusquemine can completely reverse the effects of Atherosclerosis." 

 

Trodusquemine is already proven to be safe enough it is being used in a human breast cancer study.
 

"The drug is already undergoing separate trials for treating breast cancer and diabetes, where it inhibits an enzyme called PTP1B.

The researchers found that it also stimulated the action of another protein (AMPK), which effectively mimics exercise and reduces chronic inflammation.

I invite others to help study this drug and create a group buy, once we know how much to use, how to administer it and how often to administer it. This should be of interest to those that have cardiovascular disease, cancer or diabetes and maybe more.

https://www.cnbc.com...(14)00347-3/pdf

 

 

 

[The Capybara]

Do you know the study's supplier of the trodusquemine ?

I might jump in to this one.

[Beetlejuice]

"Researchers from the University of Aberdeen claim that just a single dose of the new drug Trodusquemine can completely reverse the effects of Atherosclerosis."

Trodusquemine is already proven to be safe enough it is being used in a human breast cancer study.

"The drug is already undergoing separate trials for treating breast cancer and diabetes, where it inhibits an enzyme called PTP1B.
The researchers found that it also stimulated the action of another protein (AMPK), which effectively mimics exercise and reduces chronic inflammation.
I invite others to help study this drug and create a group buy, once we know how much to use, how to administer it and how often to administer it. This should be of interest to those that have cardiovascular disease, cancer or diabetes and maybe more.
https://www.cnbc.com....html<br> <br> https://www.metaboli...e/S0026-0495(14)00347-3/pdf

Mikey, super interested in this. Price is a factor of course but if we can get something up and running and it’s affordable to me, I’de like to be in. Don’t have anywhere near the knowledge (nor location) to arrange or reasearch where is the best supplier etc though. But happy to give a bit extra to anyone who can arrange the buy.

[Benko]

"The researchers found that it also stimulated the action of another protein (AMPK)"

 

I wonder what this means for people already taking things which stimulate AMPK e.g. metformin or in my case gymnostemma/Jiaogulan.

[Orinoco]

I'd want to join this group buy, depending on price + who orders it.

[Death2aging]

i'm in.

[ceridwen]

Yes interested

[Acetylnordopatoninol]

i would also join a group buy

[Daniel Cooper]

I'm interested depending on the source and how it needs to be administered (IV? SubQ? IM? Oral?)

 

 

 

[mikey]

I ordered the full text of the study to look for this. I will present this as soon as I read the full text.

[mikey]

In the "reversing atherosclerosis... thread, Darryl shared what's below. That trodusquemine is orally available is welcome information.

 

Darryl

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Posted 16 November 2017 - 01:55 PM

Originally, trodusquemine was an experimental treatment for obesity and diabetes, but Genaera ran out of cash before it could conduct Phase II clinical trials, and shut down in 2009. A cholesterol lowering effect was already noted in the patent (first link), but I don't know if the brief discussion of trodusquemine's potential use for treating atherosclerosis gives the current assignee, Ohr Pharma, rights for this purpose. I wish I could recall more about drug IP law: is it the compound, or the compound+potential use.

 

Anyway, there are a large number of PTP1B inhibitors (if that's the mechanism for plaque clearance), with trodusquemine notable for being orally bioavailable with a pretty low IC₅₀.

 

 

I asked Darryl to join this forum to share data.

Some things we need to know:

 

1. Dosing orally;
2. Dosing subQ;

3. Frequency of dosing or continuation of use;

4. How heat resistant (stable) MSI-1436 is for shipping to distant locations;
5. For destinations that are close to the buyer, does it need to be shipped in a "cool" container with ice;
6. Source;

7. Cost.

Everyone, please add to this list as necessary.
 

[Beetlejuice]

Mikey, I don’t seem to be getting email updates for this forum although I’ve posted here. Any suggestions on what I’ve missed?
Thanks

[The Capybara]

If someone can find the source of trodusquemine cited in:

Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine.

that would be a great help!

It might be in Materials and Methods section, but it'll be somewhere.

I don't have access to the full article, but if you're at a university chances are......

[Acetylnordopatoninol]

i posted this in the other Trodusquemine thread, but here's a presentation showing mice treated with Trodusquemine(MSI-1436) regenerating heart muscle after heart attack.

[thedarkbobo]

Interested depending on the factors above - if can take orally and price not super high.

[zorba990]

Tea contains potent inhibitors of tyrosine phosphatase PTP1B
https://www.scienced...006291X11003354
"Biochemical fractionations demonstrated that the major effective components in tea corresponded to oxidized polyphenolic compounds. This was further verified by the fact that tea catechins became potent inhibitors of PTP1B upon oxidation catalyzed by tyrosinases. When applied to cultured cells, tea extracts induced tyrosine phosphorylation of cellular proteins. Our study suggests that some beneficial effects of tea may be attributed to the inhibition of PTP1B."

So tea plus tyrosine to stimulate tyrosinase?

[mikey]

Mikey, super interested in this. Price is a factor of course but if we can get something up and running and it’s affordable to me, I’de like to be in. Don’t have anywhere near the knowledge (nor location) to arrange or reasearch where is the best supplier etc though. But happy to give a bit extra to anyone who can arrange the buy.

 

Hello Beetlejuice et al,

I have started to keep a table of those that are interested. I will enter each person that says they are interested in the table as being potentially interested.

 

The full text of the study on MSI-1436, AKA Trodusquemine (TD) is in my email - I saw that it arrived last night. I just have to catch up on my email and get to it to determine who the supplier is and, maybe with help, determine the dose that is needed for human use.

We already had "Darren" in the newsgroup "Reversing Arterial Plaque," say that TD is orally available.

The study used IV dosing and measured blood levels in mice, so, since I am not biochemically facile, we need someone who can interpret what the blood level measurements in the study equate to for humans for oral use and, perhaps for SubQ administration.

 

Then, after I entabulate all the people that are "interested" so that I/we can determine what dose we need for either oral or SubQ use and we can determine how much to order, I will get a quote from the supplier for aliquoted, lyophilized vials that are TF-free - very clean at a high percentage of purity.  

Just reporting progress.

[YOLF]

Mimics exercise? Any weight loss data? That would make it of particular interest. 

 

 

[mikey]

I'd want to join this group buy, depending on price + who orders it.

 

Noted~

[Daniel Cooper]

If someone can find the source of trodusquemine cited in:

Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine.

that would be a great help!

It might be in Materials and Methods section, but it'll be somewhere.

I don't have access to the full article, but if you're at a university chances are......

 

Multistep Inhibition of α‐Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine

 

Full article attached.

Attached Files

•  perni2018.pdf   3.37MB   30 downloads

Edited by Daniel Cooper, 09 September 2018 - 05:24 PM.

[Daniel Cooper]

Effects of hepatic protein tyrosine phosphatase 1B and methionine restriction on hepatic and whole-body glucose and lipid metabolism in mice

 

 

 

 

 

Attached Files

•  Effects of hepatic protein tyrosine phosphatase 1B and methionine restriction on hepatic and whole-body glucose and lipid metabolism in mice.pdf   665.54KB   10 downloads

[zorba990]

What happens in the body if all that plaque 'melts'? How is it excreted...that could be a considerable amount of calcium

[YOLF]

Well it's being touted as safe and any immediate and serious side effects such as hypercalcemia, hypercholesterolemia, or hyperlipidemia would presumably have been detected, so whatever it's doing, if we decide to be optimistic, is leading to rapid elimination or extensive metabolism of the byproducts of plaque breakdown. Perhaps the foam cells in this scenario are able to produce conditions that rapidly degrade these byproducts by enzymatic action? I think it is easy to assume that our immune cells (which create the plaque in the first place) are able to digest a nice range of toxic materials, and that perhaps that range is extended by the Trodusquemine by the removal of a few important lynch pins that we lack or the activation of genetics that may have been silenced by aging.

[The Capybara]

 

Multistep Inhibition of α‐Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine

 

Full article attached.

 

 

Thanks for uploading that article.

It seem that they are synthesizing the compound themselves. Their synthesis seems pretty straightforward and has high yields, although they seem to be a little cryptic on details, referring to other articles, which then reference other articles for the specific information. It seems as though we'll have to have a custom synthesis done.

There are a few labs in China that I trust, though we now have some tariffs importing from there and China is now imposing environmental fees (a good thing).

[mikey]

i'm in.

 

Noted ~

 

Hello Everyone.

I received the full text of the study "Pharmacological inhibition of protein tyrosine phosphatase 1B (PTP1B) protects against atherosclerotic plaque formation in the LDLR mouse model of atherosclerosis."

 

Now there's the job of translating dosing of mice to HED (human equivalent dose). This is 

 

Fortunately, my assistant with degrees in chemistry and physics is coming to work Monday and Tuesday.

We will also investigate the human breast cancer study.

https://clinicaltria...how/NCT02524951

 

It says: July 2017 (Final data collection date for primary outcome measure)

 

So, we will see what is eventually presented. 

 

Please chime in and bring this to the attention of knowledgeable friends. (I wish that niner was still around!)

 

We will work through this equation and report to you.

Michael

[The Capybara]

Noted ~

 

Hello Everyone.

I received the full text of the study "Pharmacological inhibition of protein tyrosine phosphatase 1B (PTP1B) protects against atherosclerotic plaque formation in the LDLR mouse model of atherosclerosis."

 

Now there's the job of translating dosing of mice to HED (human equivalent dose). This is 

 

Fortunately, my assistant with degrees in chemistry and physics is coming to work Monday and Tuesday.

We will also investigate the human breast cancer study.

https://clinicaltria...how/NCT02524951

 

It says: July 2017 (Final data collection date for primary outcome measure)

 

So, we will see what is eventually presented. 

 

Please chime in and bring this to the attention of knowledgeable friends. (I wish that niner was still around!)

 

We will work through this equation and report to you.

Michael

That study was cancelled, so the results will be unknown.

It was most likely cancelled when Genaera, the pharma company developing trodusquemine (MSI-1436), went belly up.

What can be gleaned from the study filing is their intended human dose range, though that isn't available on the federal clinical study website.

[mikey]

Mikey, I don’t seem to be getting email updates for this forum although I’ve posted here. Any suggestions on what I’ve missed?
Thanks

 

Missed? Hmmm. I now have 8 people that are interested and I am still looking through this stream, and posting in other forums trying to collect a volume of people.

Since CVD is number one in degenerative disease of aging, I would think that we might experience a good number for a group buy. At 8 people today this group buy is only a few days old. Please spread the word. The more we have the lower our cost of manufacturing will be.
 

I PM'd Darryl to ask to help analyze the study. The study looked at seven dosing schemes, all were IV drips for two hours, though.

 

Translating how this is applied to humans, especially for oral use, since Darryl said that this would work orally, is the next challenge.

 

I can buy from quality chemical manufacturers, so we shall look at the supplier for the study and then look at synthesizing companies, such as Genentech and a couple that I have purchased from before.

 

My Ph.D. assistant comes to work for two days Monday and Tuesday. I will give him this job and we will see what he comes up with. Hopefully, Darryl will respond and chip in, as he appears to know chemistry. 

I will send this to you as a PM just in case you don't receive this update.

[mikey]

If someone can find the source of trodusquemine cited in:

Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine.

that would be a great help!

It might be in Materials and Methods section, but it'll be somewhere.

I don't have access to the full article, but if you're at a university chances are......

 

I have recorded this study. Thank you!

 

However, more relevant to us is the human study that administered TD IV for two hours at 7 dosing schemes. That's where we will begin analysis to see what might be safe and effective for humans orally and SubQ. (I don't want IV and I assume that a majority don't want IV, much less a two-hour IV dip. I had a doctor that would do this for me, but he retired.)

 

Again, I wish niner was around. His knowledge of chemist is missed.

"The researchers found that it also stimulated the action of another protein (AMPK)"

 

I wonder what this means for people already taking things which stimulate AMPK e.g. metformin or in my case gymnostemma/Jiaogulan.

 

Me, too, Benko. I take Metformin as an anti-aging supplement.

[mikey]

 

Multistep Inhibition of α‐Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine

 

Full article attached.

 

 

Ah. I attach the rat study.

Please analyze to determine what human dosing might be.

Also, this group buy now has ten people. We are only a few days old. Spread the word. The more the lower our cost. I wonder if my Ph.D. assistant, Robert, will want to participate after he sees this tomorrow when he comes to work. Beat the drums and get more participants. 
 

Beetlejuice

interested

Orinoco

Depending on price and who orders it

The Capybara

might jump in to this one.

Death2aging

I’m in

Ceridwen

Yes, interested

Acetylnordopatoninol

Would also join

Daniel Cooper

Depending on source and how administered

SumWon

Interested

thedarkbobo

Interested if oral and not super-hi priced

Mikey

 

 

If I am missing anyone, please let me know.

Attached Files

•  Pharmacological inhibition of protein tyrosine phosphatase 1B (PTP1B) protects against atherosclerotic plaque formation in the LDLR mouse model of atherosclerosis.pdf   590.37KB   17 downloads

Edited by mikey, 09 September 2018 - 09:40 PM.

[Daniel Cooper]

In case we haven't posted this one:

 

The protein tyrosine phosphatase 1B inhibitor MSI-1436

stimulates regeneration of heart and multiple other tissues

 

 

 

 

Attached Files

•  The protein tyrosine phosphatase 1B inhibitor MSI-1436 stimulates regeneration of heart and multiple other tissues.pdf   2.46MB   17 downloads

Edited by Daniel Cooper, 09 September 2018 - 10:29 PM.