NKISK pentapeptide, the HOLY GRAIL of PE?

Sounds like an idea that will never be tested by anyone in this community including the author. So I’m out.

What could possibly go wrong!?(emphatic expression) Lol

Anyone want to take one for the team?

Obviously kidding.

No but in all seriousness, this could be a god send to PE. If anyone knows about peptides come forth.

Btw I’m no expert in anything. But I’ve had success with heat and hanging and can confirm that if NKISK could be used and it was as effective in humans that it would be so much easier to accomplish higher strains leading to permanent gains.

Well, we have seen the harvest on the anabolic steroid group already. We are only just getting to know the long term effects on HGH abuse. And it is looking bad. Bodybuilding community has seen the dead rate raising with the aging generation which got involved with it in the first place. Next to come is the IGF-1 abusing group, but we need to wait for few years. I am in the line, with involvement in all these groups. I am talking about long term effects on heart here.

Some would say that taking them separately only short periods all of them could be used rather safely, but combining them have been demonstrated to raise the risks at multiple rate.

Can´t even imagine what would be in several peptide groups, I would imagine there will be whole a lot new cases of alzheimer, parkinson etc.
Many of them can can pass through the blood brain barrier with ease, which have not been the usual scenario with the old time stuff mentioned above.

As a longterm ex-abuser of the body enhancement substances I would recommend to stay away from the peptides in general.

But you are right about one thing. PE community is waiting for the catalyst to arrive.
We are in the same situation bodybuilding was before Dianabol arrived in 60`s.
And if we take a look what happened since, the development has been overwhelming. The whole scientific aspect has flourished in general, not only the steroid aspect. . PE is in the need of its own DIanabol.

Thank you for your perspective. I am confused by this part: The “and it is looking bad” part you are referring to is strictly steroid use correct? Or is there evidence out now that HGH releasing peptides are also “bad”?

The problem is the long term effects.. there is no way of knowing unless you try. It could be totally safe, and we are missing out on an awesome drug that can elevate our results. Or it could be dangerous, and we obtain results at the cost of our health. It is a gamble.

I have a feeling it is not that dangerous but my precious health I cannot risk. Maybe if I were dying already I wouldn’t care.

Since I am no doctor and have no knowledge of how these things work, my guess for what is worth with what I’ve read about peptides and such thus far, what would happen is:

The body would eliminate the excess NKISK injected and it would go to work as predicted. This is because HGH or IGF-1 work similarly. They only activate the pituitary to release the maximum HGH possible that is naturally capable of releasing. So it just triggers the gland. It is very tailored. High specificity drug. Whereas steroids are synthetic replicas of testosterone, etc, which create abnormal levels of the hormone and shut down the natural release of testosterone, so people have to take PCT’s after a cycle to restore the natural testosterone system. So the difference is quite high between the two.

My main concern with NKISK is that in repeated amounts injected into the same areas, there could be triggering an imbalance in the cells, etc. And imbalances usually create problems, and that is where cancer could form, out of that imbalance. But it could be wrong, maybe such a small peptide is not strong enough to create an imbalance. Maybe an injection once a week is not enough to cause major disruption in cell functionality. We are only after breaking the binding in the fibrils anyway.

Does anyone know of any other short peptide drugs which are FDA approved, that would be of similar length in amino acids, and used repeatedly?

I am not sure how long these HGH or IGF-1 releasing peptides have been out and people been using them. Of course comparing NKISK to these would be wrong, as they are not the same. But as a proxy for their safety, it would help to narrow down what we would be dealing with here.

Database of FDA-approved peptide and protein therapeutics.
THPdb: Database of FDA-approved peptide and protein therapeutics - PubMed

But it doesn’t load for me

An interesting overview of the peptide industry :

Therapeutic peptides: Historical perspectives, current development trends, and future directions

https://www.sci encedirect.com/ … 968089617310222

Now this is interesting:

NKISK, a small polycationic pentapeptide with two lysine residues, competitively inhibits the binding of fibronectin to decorin by mimicking a sequence in the decorin molecule that is presumed to be the fibronectin binding site.

Cationic peptides: Cationic antimicrobial peptides : issues for potential clinical use - PubMed

antimicrobial peptides: https://en.m.wi kipedia.org/wik … robial_peptides
"Antimicrobial peptides are a unique and diverse group of molecules, which are divided into subgroups on the basis of their amino acid composition and structure.[2] Antimicrobial peptides are generally between 12 and 50 amino acids. These peptides include two or more positively charged residues provided by arginine, lysine or, in acidic environments, histidine, and a large proportion (generally >50%) of hydrophobic residues.[3][4][5]

Also note the resemblance to the effects of Gentamicin, and Tobramicin, which are antibiotics in tendon lengthening.

NKISK is hidrophilic, not acidic. Easy to dilute in water.

Secretory Expression of a Chimeric Peptide in Lactococcus lactis: Assessment of its Cytotoxic Activity and a Deep View on Its Interaction with Cell-Surface Glycosaminoglycans by Molecular Modeling
Secretory Expression of a Chimeric Peptide in Lactococcus lactis: Assessment of its Cytotoxic Activity and a Deep View on Its Interaction with Cell-Surface Glycosaminoglycans by Molecular Modeling | Semantic Scholar
"Nowadays, cancer remains a major cause of death affecting millions of people. Currently, the antimicrobial peptides (AMPs) as potent anticancer therapeutic agents offer specificity and low levels of side effects in cancer therapy."

Based on the above, the case for NKISK as a cancer causing agent seems to be diminished.

Interestingly, Cipro, as strong common antibiotic, has had the side effects of rupturing tendon. FDA Warns That Cipro and Similar Antibiotics May Rupture Tendons

I think we are dealing with something similar to an antibiotic in the form of a peptide.

The difference between NKISK and using Gentamicin though for tendon lenghtening is that once gentamicin was removed, the tendon stopped stretching and it’s stiffness and modulus returned to normal. However, with NKISK the effects on tendon lengthening seem to be more pervasive. As in some of the tests were rats were sacrificed 28 days later, there were still significance that it works, albeit less strain, but still pervasive enough. Which is also a good thing as you would not want permanently weaker tendons.

Once side caution would be how it would affect accompanying tendons in the body, proximal regions to the area treated, and if it would have a systemic effect on collagen in other tendons like cipro has.

“Gentamicin
Gentamicin is excreted by glomerular filtration, and toxicity may occur if the dose is not adjusted for underlying renal impairment. Cationic amino groups (NH4+) on the drug bind to anionic megalin on the brush border of proximal tubular epithelial cells, and the drug is then internalized by endocytosis. The drug accumulates in proximal tubular cell lysosomes and can reach 100 to 1000 times its serum concentration. The drug interferes with cellular energetics, impairs intracellular phospholipases, and induces oxidative stress; however, the exact pathways culminating in tubular necrosis remain unknown.12”

“Oxidative stress occurs when excess oxygen radicals are produced in cells, which could overwhelm the normal antioxidant capacity. When the concentration of reactive species is not controlled by internal defense mechanisms such as antioxidants (tocopherols, ascorbic acid, and glutathione) or enzymes involved in oxygen radical scavenging (catalase, peroxidase, and superoxide dismutase, SOD), oxidative damage occurs to proteins, lipids, and DNA, which could lead to cytotoxicity, genotoxicity, and even carcinogenesis when damaged (mutated) cells can proliferate. Oxidative stress could results from the following: (1) the presence of xenobiotics, (2) the activation of the immune system in response to invading microorganisms (inflammation), and (3) radiation, which makes oxidative stress a common denominator of toxicity or stress. In this chapter, the reader will find a variety of assays to measure oxidative stress and damage.”

“Xenobiotics have been defined as chemicals to which an organism is exposed that are extrinsic to the normal metabolism of that organism. Without metabolism, many xenobiotics would reach toxic concentrations. Most metabolic activity inside the cell requires energy, cofactors, and enzymes in order to occur. Xenobiotic-metabolizing enzymes can be divided into phase I, phase II, and transporter enzymes. Lipophilic xenobiotics are often first metabolized by phase I enzymes, which function to make xenobiotics more polar and provide sites for conjugation reactions. Phase II enzymes are conjugating enzymes and can directly interact with xenobiotics but more commonly interact with metabolites produced by phase I enzymes. Through both passive and active transport, these more polar metabolites are eliminated. Most xenobiotics are cleared through multiple enzymes and pathways. The relationship between chemical concentrations, enzyme affinity and quantity, and cofactor availability often determine which metabolic reactions dominate in a given individual.”

5 different antimicrobial peptides and their effects on red blood cells and cytotoxicity

https://www.ncb i.nlm.nih.gov/p … les/PMC5917001/

Seems the effect is dependent on the specific sequence of the peptide and the salt that is used to replace the TFA when cleaving the resins when the custom peptide is made.

As an example, Pexiganan which has plenty K’s in the sequence, had lower hemolysis (death of blood cells) at higher concentrations Fig.2 using AcO or CL salts. And lower Cytotoxitity (Cytotoxicity is the quality of being toxic to cells. ) with the CL salt replacement.

Hemolysis is dose dependent, as at 32 ug/ml there was 0% hemolysis, but at 256 ug/ml there was 5-8%.

It would be good to do a panel on NKISK hemolysis effect and cytotoxic with TFA, AcO, and CL, at different doses to estimate the effect.

Perhaps at low enough doses the stress on the cells would not be a lot, and still accomplish the task at hand.

I was talking about known adverse effects of steroids alone. The Group started to use steroids seriously have started to drop death like flies at their sixties with heart related conditons. Addition to that I was talking about of known adverse effects showing at multiple rate combining the the use of anabolic steroids and growth hormone.
Rate of premature sudden deaths raises with anabolic steroids and is magnified with adding GH. That is looking bad as the first population which have had GH widely available is now in their fifties and the signs are there.
Insulin-like growth factor has been available not that long so we don´t know yet.

I dont know what you were aiming to say here but you have it all wrong concerning the use of exogenous somatropin and insulin-like growth factor 1. It does not work that way.

Peptides ,sarms? Nobody knows. Earlier combounds had been tested and documented way better than any of thee peptides. Still long term effects had remain unknown until now.

From a person who responded to this question: What is the difference between peptides and steroids?

“Peptides are messenger proteins that signal your pituitary gland and testicles (in males) to ramp up hormone production (growth hormones or testosterone).

Anabolic steroids are molecularly modified versions of the male hormone testosterone, designed to emphasize muscle healing and growth.

Peptides, which originally came out of the Life Extension community, can only signal the pituitary gland or testicles to produce high, but normal levels of hormones. The pituitary gland and testicles can only produce hormones up to a certain level. At best, a peptide regimen could produce the growth hormone and testosterone levels of someone in their 20’s.

Anabolic steroids, in contrast to peptides, can be taken in huge dosages, to the level of 100x or 1000x the normal level of a human male (5–12 mg/day). So a steroid user can have hormone levels that are impossible to achieve naturally.

The drawback to anabolic steroids as compared to peptides, is that when the body detects that high level of anabolic steroids in the system (which it interprets as testosterone), it will shut down natural testosterone production in the testicles and will convert some of the steroid molecules in the body, to estrogens, in order to maintain hormonal balance. Basically, the testicles will shrink and when the steroid usage is discontinued, other fertility hormones will need to be taken to restore testicular function and sperm production.

In contrast, peptides simply signal our glands to turn on hormone output. By using our own glandular system, peptides will NOT cause the hormone disruptions and glandular disruption that steroids cause. But, since Peptide usage will only cause high-normal hormone output, the effects are not as dramatically strong as high dose anabolic steroids usage.

Basically one could be on a peptide regimen for decades, for life extension and healing properties, with little problems. But long term (decades) of anabolic steroid use, at superhuman doses, will commonly lead to adverse health issues (heart problems, arteriosclerosis, liver cysts/cancer, infertility).”

As just a suggestive proposition, we could do a crowdfunding sort of thing for those of us who are interested, to have NKISK sent to a lab to test for cytotoxicity and hemolysis or some other tests. There are services out there that can be used, sort of like outsourcing a lab to do the tests for you. There are also in vivo test services.

This could all be easier if one were to do a crowdfunding campaign in a popular platform like kickstarter, but the veil of secrecy that is PE would have to be lifted, so not many would be comfortable with that, including myself.

Just throwing that out there. If people would be interested we could crowd source via bitcoin, as long as thundersplace is ok with it, and members understand that test results won’t be definitive but purely ‘informational’, we could do it.

Not sure what the costs would be, but I would say we’d need 3 different doses, 5mM, 20mM, and 50mM. And for each, test with each different salt TFA, AcO, and CL. Per test I think we’d need 1-2mg of NKISK. So that is around 20mg total. For 100mg I checked with Biomatik, and they quoted $232 with AcO salt replacement. With TFA it is much cheaper because the TFA is actually the salt that is left initially, but it is considered more toxic, and usually just used for in vitro studies. AcO and CL are more bio friendly and used in cell culture assays. We could eliminate TFA altogether as well. And just have tests with AcO and CL. The tests themselves would be another cost, which I will look into.

Anyway, Rome wasn’t built in a day.

It would be awesome to get a group of university students interested in this. If they had funds from their university to do a study I am sure they would be all over this.

Please. Once again. Read what you wrote, as your sentence makes no sense. Human Growth Hormone (somatotropin). Insulin-like growth factor 1 (somatomedin C). They do something else than you described. Study them if you are going to post anything more of them.. And no lectures this time.

I know this is siderail, but you brought these substances in to this context.

If you were meaning to say something else, you should say it. Otherwise you are supposed to be eaten alive :)

Where is said that body would eliminate the excess NKISK injected, I did not really catch it anywhere.

Seems like I dd bring them in to context. So be it.

And you were talking about GH or IGf-1 releasing peptides.

Guess it was my bad then. Sorry to interrupt. Go on as you were.

But the question is still relevant. How is the excessive NKISK eliminated. By which mechanism?

When it gets to in to bloodstream, and involved with your collagenous aortic tissues and valves, what would happen then?

No worries :)

I guess what I meant was this:

“For the average person, the proper dose for a GHRP or MOD GRF1-29 (previously known as CJC is 100 mcg each, for a total of 200 mcg done two to three times daily. The 100 mcg suggestion is called “saturation dosage”. This means that 100 mcg is about all that your body can absorb at one time. For women, the saturation dosage of 50 to 75 mcg will probably work very well.

Anything over 100 mcg per peptide, the body will just discard, so it is really not financially advantageous to go beyond 100 mcg doses.”

I can’t confirm it is correct or valid, just what some dude said