1569 replies to this topic

[medievil]

Trough what mechanism does that cause cancer then, keep digging till you find a place you can put a stop sign, my philosofy, dont give up anything is possible (or die trying wich i often do haha).

[Xenix]

Group latencies to find the submerged platform in the Morris water maze task of spatial memory are shown. Five minutes before beginning testing 24 month old mixed sex (3 male and 3 female/group) Sprague Dawley rats were administered dihexa (2 mg/kg) orally by gavage (suspension in isotonic NaCl), on a daily basis.

http://m.jpet.aspetjournals.org/content/early/2012/10/10/jpet.112.199497.full.pdf

I know that these rat model trials are notorious for severely overdoing the dosage, but damn; if I followed that same dose, then I (weighing 80kg) would be taking 160mg/day - so a gram of Dihexa would last me about 6 days, right? Any stabs in the dark on what a more reasonable dosage for a human my size would be? just trying to gauge this price-wise.

Edited by Xenix, 15 February 2013 - 11:16 PM.

[medievil]

Im sure youll find a substance saying "antagonizes the carcinogenic effect of angiotension" or whatever, just needs digging, curcumin and co act on so many pathways we could take the risk if your family is without cancer to assume that overpowers the carcinogenic effect. DA and risk taking, da gives cancer, money, sex, and more.

[Rior]

By what pathway does it promote cancer? simply inhibit the next step.

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).

Right there, unfortunately. If Dihexa is a positive allosteric modulator of the c-Met receptor, I would certainly think that would qualify as causing "aberrantly active c-Met activation." Granted, I certainly home I'm wrong and feel that it may be likely that I am considering they're about to start IND tests, however I feel this c-M et overactivation is certainly something worth bringing up for discussion.

As far as my knowledge goes Dihexa is a AT4 receptor antagonist. And if we look the evidence outlined in from previously linked slide-presentation if anything the compound inhibits cancer growth. And I do not believe that rebound effects of angiotensine levels after cessation of Dihexa treatment would be a big problem because angiotensine IV is itself at the end of angiotensin metabolism pathway.

I think the bigger problem in terms of cancer risk is increasing Your angiotensine II levels by taking usual AT-1 receptor antagonists (for example losartan) - this would increase the angiotensine II levels that would also increase the levels of it's metabolites angiotensine III and IV therefor increasing cancer risk via angiotensin IV signaling.

I did some quick googleing and found even some evidence for the mechanism I described above.

Please re-read my first post. I made it expressly clear that I had a conversation with Lewis Rumpler, the CEO of M3 Biotechnology--the industry behind Dihexa. That said, I am telling you that Dihexa is not simply an AT4 receptor antagonist. To say that it is would be entirely incorrect. Let me say it again: "MM-201 (Dihexa) is a small molecule agonist of HGF or Hepatocyte Growth Factor. HGF is the obligate ligand of c-Met, a [tyrosine] receptor kinase and the putative [eg, expected to be] AT4 receptor." A"ligand" can be defined as a molecule that activates a receptor. So a positive agonist of that ligand will increase the amount of that ligand, thereby increasing the frequency the c-Met receptor is binded. This is the EXACT OPPOSITE action of any of the AT4 receptor antagonists you have mentioned. Well, not the exact opposite, as Dihexa affects the production of HGF, whereas the AT4 receptor antagonists directly affect the receptor itself. Either way, completely different mechanisms of actions.

Now that that's out of the way, let's evaluate the mechanism of action behind Dihexa. This is the above statement: "MM-201 (Dihexa) is a small molecule agonist of HGF or Hepatocyte Growth Factor. HGF is the obligate ligand of c-Met, a [tyrosine] receptor kinase and the putative [eg, expected to be] AT4 receptor." So that said, if a AT4 receptor antagonist acts as anti-cancer, then would it be appropriate that increased binding to the AT4 receptor may increase cancer? Seeing as the AT4 receptor is seen to be potentially analogous to the c-Met receptor, and I just listed how overactivity of the c-Met receptor was directly linked to the increased growth of tumors and angiogenesis to said tumors. Again, I want to make it clear that I am NOT CLAIMING DIHEXA CAUSES CANCER. Absolutely not. All I'm saying is that overactivity of the c-Met receptor has been potentially linked to increase tumor growth.

I want to remind that Dihexa has seen a number of trials, and it seems thus far that it is not cancer-inducing--considering it's seen great success in its trials. ALL I'm saying is that, if its mechanism of action is to act as an agonist of HGF--the obligate ligand of the c-Met receptor--then perhaps this may cause problems. Now to bring up an alternative reason for why it may be safe, perhaps there is a self-limiting mechanism in the brain that keeps increased HGF from causing cancerous problems with the c-Met receptor. After all, directly agonizing the c-Met receptor is not the same as agonizing the production of HGF.

TL;DR, Dihexa is not something I would suggest experimenting with on yourself until there are more studies. I don't say this about many supplements, however this one in particular seems worth noting for my above reasons^. So I would suggest reading these reasons if you're considering it.

Edit: Last note, Dihexa is also known as MM-201. The above slide presentation you linked to refers to PNB-0718, PNB-0405 and PNB-0408. These are all completely different molecules than MM-201.

Edited by Rior, 16 February 2013 - 07:35 AM.

[mait]

By what pathway does it promote cancer? simply inhibit the next step.

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).

Right there, unfortunately. If Dihexa is a positive allosteric modulator of the c-Met receptor, I would certainly think that would qualify as causing "aberrantly active c-Met activation." Granted, I certainly home I'm wrong and feel that it may be likely that I am considering they're about to start IND tests, however I feel this c-M et overactivation is certainly something worth bringing up for discussion.

As far as my knowledge goes Dihexa is a AT4 receptor antagonist. And if we look the evidence outlined in from previously linked slide-presentation if anything the compound inhibits cancer growth. And I do not believe that rebound effects of angiotensine levels after cessation of Dihexa treatment would be a big problem because angiotensine IV is itself at the end of angiotensin metabolism pathway.

I think the bigger problem in terms of cancer risk is increasing Your angiotensine II levels by taking usual AT-1 receptor antagonists (for example losartan) - this would increase the angiotensine II levels that would also increase the levels of it's metabolites angiotensine III and IV therefor increasing cancer risk via angiotensin IV signaling.

I did some quick googleing and found even some evidence for the mechanism I described above.

Please re-read my first post. I made it expressly clear that I had a conversation with Lewis Rumpler, the CEO of M3 Biotechnology--the industry behind Dihexa. That said, I am telling you that Dihexa is not simply an AT4 receptor antagonist. To say that it is would be entirely incorrect. Let me say it again: "MM-201 (Dihexa) is a small molecule agonist of HGF or Hepatocyte Growth Factor. HGF is the obligate ligand of c-Met, a [tyrosine] receptor kinase and the putative [eg, expected to be] AT4 receptor." A"ligand" can be defined as a molecule that activates a receptor. So a positive agonist of that ligand will increase the amount of that ligand, thereby increasing the frequency the c-Met receptor is binded. This is the EXACT OPPOSITE action of any of the AT4 receptor antagonists you have mentioned. Well, not the exact opposite, as Dihexa affects the production of HGF, whereas the AT4 receptor antagonists directly affect the receptor itself. Either way, completely different mechanisms of actions.

Now that that's out of the way, let's evaluate the mechanism of action behind Dihexa. This is the above statement: "MM-201 (Dihexa) is a small molecule agonist of HGF or Hepatocyte Growth Factor. HGF is the obligate ligand of c-Met, a [tyrosine] receptor kinase and the putative [eg, expected to be] AT4 receptor." So that said, if a AT4 receptor antagonist acts as anti-cancer, then would it be appropriate that increased binding to the AT4 receptor may increase cancer? Seeing as the AT4 receptor is seen to be potentially analogous to the c-Met receptor, and I just listed how overactivity of the c-Met receptor was directly linked to the increased growth of tumors and angiogenesis to said tumors. Again, I want to make it clear that I am NOT CLAIMING DIHEXA CAUSES CANCER. Absolutely not. All I'm saying is that overactivity of the c-Met receptor has been potentially linked to increase tumor growth.

I want to remind that Dihexa has seen a number of trials, and it seems thus far that it is not cancer-inducing--considering it's seen great success in its trials. ALL I'm saying is that, if its mechanism of action is to act as an agonist of HGF--the obligate ligand of the c-Met receptor--then perhaps this may cause problems. Now to bring up an alternative reason for why it may be safe, perhaps there is a self-limiting mechanism in the brain that keeps increased HGF from causing cancerous problems with the c-Met receptor. After all, directly agonizing the c-Met receptor is not the same as agonizing the production of HGF.

TL;DR, Dihexa is not something I would suggest experimenting with on yourself until there are more studies. I don't say this about many supplements, however this one in particular seems worth noting for my above reasons^. So I would suggest reading these reasons if you're considering it.

Edit: Last note, Dihexa is also known as MM-201. The above slide presentation you linked to refers to PNB-0718, PNB-0405 and PNB-0408. These are all completely different molecules than MM-201.

Thank You for clearing it! My mistake.

[Olon]

Who is interested in potency?
It is said to be seven times more effective than BDNF, so with a good TrkB agonist one just would have to wait seven times longer for the same effect.
I find it's time that someone releases N-acetylserotonin as a dietary supplement.

[Xenix]

Anybody know its CAS number? I want to ask around for more quotes.

Edited by Xenix, 17 February 2013 - 03:49 PM.

[nootlyinclinded]

I just contacted a company to have 500mg of Dihexa synthesized for me. It should arrive after the 3 week mark. Hopefully, the use of this product won't give me cancer. I will most likely start a log once I receive said peptide.

[spermidine]

what is this dihexa product i dont know of. it doesnt have any reliable links to explaination of what it consists of. definately not wkipedial entry....

[kylehere]

I just contacted a company to have 500mg of Dihexa synthesized for me. It should arrive after the 3 week mark. Hopefully, the use of this product won't give me cancer. I will most likely start a log once I receive said peptide.

any news?

[Optimism]

I just contacted a company to have 500mg of Dihexa synthesized for me. It should arrive after the 3 week mark. Hopefully, the use of this product won't give me cancer. I will most likely start a log once I receive said peptide.

Oh boy, this is going to be an interesting thread.

[nootlyinclinded]

I just contacted a company to have 500mg of Dihexa synthesized for me. It should arrive after the 3 week mark. Hopefully, the use of this product won't give me cancer. I will most likely start a log once I receive said peptide.

any news?

Yes, I should be receiving my order today. I might end up preparing it for IM injection in order to increase the effectiveness of it since I will be taking a considerably small dose compared to my counterpart who plans to use it at a higher dose.

[megatron]

I just contacted a company to have 500mg of Dihexa synthesized for me. It should arrive after the 3 week mark. Hopefully, the use of this product won't give me cancer. I will most likely start a log once I receive said peptide.

any news?

Yes, I should be receiving my order today. I might end up preparing it for IM injection in order to increase the effectiveness of it since I will be taking a considerably small dose compared to my counterpart who plans to use it at a higher dose.

How much did you buy and how much did you pay for it?

[nootlyinclinded]

I bought 500mg. I'm not going to go into how much I paid for it and which company I went through as they specifically stated it was not for human consumption. Anyways, I just received it. It wasn't as hydrophobic as I expected it to although it does get dissolved in water with enough stirring. Weighing out 5mg even on a miligram scale (a .001 scale) is a bitch. Luckily, I had some miligram scoops with me and decided just to use about 3. Should be accurate enough.

[spermidine]

what is this dihexa product i dont know of. it doesnt have any reliable links to explaination of what it consists of. definately not wkipedial entry....

[nootlyinclinded]

Please refer to the beginning posts.

[Godof Smallthings]

Did the company state why it was not for human consumption?

[Rior]

As much as I might have said it's dangerous to try this... I'm pretty excited to hear your results.

[BioFreak]

what would be the test setup anyways? take a minimal dose and then learn something and try to recall it the next day?

[Olon]

Weighing out 5mg even on a miligram scale (a .001 scale) is a bitch. Luckily, I had some miligram scoops with me and decided just to use about 3. Should be accurate enough.

Didn't you read about the potency?
That stuff is in in one league with LSD. What you need is in the ng scale.

[nootlyinclinded]

Weighing out 5mg even on a miligram scale (a .001 scale) is a bitch. Luckily, I had some miligram scoops with me and decided just to use about 3. Should be accurate enough.

Didn't you read about the potency?
That stuff is in in one league with LSD. What you need is in the ng scale.

Yes, obviously, I read about the potency; however, if you were to make a human equivalent dose considering in one study that rats were given 2mg/kg then you'd realize that a person of my weight (150lbs) would actually need about 20mgs. Please do not insult my intelligence.

[Logic]

I have been looking at what the effects of hepatocyte agonism may be:

"...When the liver is damaged it produces too many bile duct cells and not enough cells called hepatocytes, which the liver needs to repair damaged tissue..."
http://www.crm.ed.ac...t-liver-disease

[arcticjoe]

honestly i would try 0.5mg first, i've consumed plenty of substances where 20mg would have landed me into big trouble. you have to keep in mind there is no human data, rat studies and dosages do not mean much.

[Xenix]

honestly i would try 0.5mg first, i've consumed plenty of substances where 20mg would have landed me into big trouble. you have to keep in mind there is no human data, rat studies and dosages do not mean much.

...like what?

Edited by Xenix, 14 March 2013 - 10:23 AM.

[Olon]

Please do not insult my intelligence.

Sorry, I didn't want to insult you. I think you have to admit that what you are doing is somewhat hardcore, so please be tolerant when you get unexpected reactions.

[humph]

Animal to animal, say rat to human, dosing requires a conversion.

rule of thumb for rat to human dosage conversion is to multiply the rat dosage by 0.162 (37/6). We need a lot less per kg.

http://www.fda.gov/d...s/UCM078932.pdf

[megatron]

Did you try it yet?

[nootlyinclinded]

Please do not insult my intelligence.

Sorry, I didn't want to insult you. I think you have to admit that what you are doing is somewhat hardcore, so please be tolerant when you get unexpected reactions.

Yes, and I have considered the consequences of such experimentation. Despite the warnings and despite possible cancerous side effects, I have gone through with it. I have fully considered the consequences and fully accept them.

[arcticjoe]

Bromo dragonfly, desoxypipadrol, other rcs

Sent from my GT-I9300 using Tapatalk 2

Edited by arcticjoe, 15 March 2013 - 10:20 AM.

[Animal]

Please do not insult my intelligence.

Sorry, I didn't want to insult you. I think you have to admit that what you are doing is somewhat hardcore, so please be tolerant when you get unexpected reactions.

Yes, and I have considered the consequences of such experimentation. Despite the warnings and despite possible cancerous side effects, I have gone through with it. I have fully considered the consequences and fully accept them.

How could you have fully considered the consequences when even the short term physiological effects of Dihexa on humans is largely unknown? I expect a substance with such a potent effect on synaptogenesis will have unpredictable psychotropic effects which may be far from positive.

Do you even know how long a single dose will exert an effect on your neurology? At least admit you are being somewhat reckless in this endeavor.

I don't want to discourage you, since I am extremely interested in the outcome of your experiment. But what is it you hope to achieve through this trial that can't wait a year or two for further human testing to be done?