# GHRH cjc1295 / cjc 1293 / mod GRF(1-29) differences



## gymrat827 (Dec 17, 2011)

Basically anytime you take a peptide and swap out an amino acid for another you look at it to see if it still binds to its receptor or acts the way the original compound will act. If not then your change was worthless. 

But if you swap out an amino acid and you get the same effects as the original compound it becomes what is known as an analog.

All of these things are simply analogs of GHRH (Growth Hormone Releasing Hormone). Thats it.

Well before those few CJC-1295 studies analogs were created. 15 amino acids were lopped off because they had no value for GH release. That left 29 amino acids and they called that Growth hormone Releasing Factor (1-29) or GRF(1-29). Thats all GRF(1-29) is... it is the native hormone GHRH (with the inactive tail removed). The prescription drug for GRF(1-29) is sold under the name Sermorelin. 

But native GHRH is released from the brain and barely travels any distance to the pituitary so it isn't subject to degradation from plasma enzymes. GHRH works in our body and in pigs and rats and chickens.

But if you want to inject it, it has to travel in the blood stream where it is subject to degradation. So if you inject GRF(1-29) or GHRH into a body it will degrade withing a few minutes. Sure some will bind in the pituitary but most will not. So what they did was determine EXACTLY what was happening. Cleavage was occurring at the 2nd position so one analog that was created swapped Arginine for the D form of Arginine (D-Arg) at that position. Thats it.

Now that analog in rats I believe lasted 30 minutes but in humans still less then 10 minutes.

Along the way many people made many different analogs. You can swap amino acids like we just discussed or you can add side chains. The side chains will protect the vulnerable amino acid. It acts as a stiff arm. Of course adding side chains could mean the peptide no longer works so it has to be tested to see it it will still bind to its receptor (or if it is a receptor-less peptide if it still behaves as the original).

Pegylation is often used to create a longer lasting analog. Often though when you create an analog w/ side chains or Pegylation you give the peptide longer life but reduce its binding affinity (attraction) for its receptor. The analog IGF-1 LR3 has a longer life then IGF-1 (provided it isn't bound to a binding protein for survival) but it has a weaker affinity for the IGF-1 receptor. The same thing for the DES form of IGF-1.

Amino acid swaps to create analogs are done to strengthen the peptide but also to make the synthesis process easier.

When the CJC-1295 study was done they needed comparisons for the structure they really wanted to test. What they really wanted to do was take their invention called a Drug Affinity Complex, DAC for short and attach it to all sorts of things. SO Conjuchem the makers patented it.

DAC is like velcro. It clings to albumin. Albumin exists in plasma. In fact GH when it binds to a receptor does many things besides initiate IGF-1 transcription. It also initiates transcription of albumin. That is how albumin can be made. But that is an aside.. back to the main point. Albumin has a long life and so if you can get something to cling to it for protection then maybe you can get that something to have a long life as well.

Albumin has a long life in rats and rabbits...maybe as long as 30 days [I forget?]. In humans it is a lot less... 10 days? [I'm sorry I forget exactly]. The point is when you look at the animal study for CJC-1295 you can not rely on the numbers because of the difference in albumin life.

Conjuchem wanted to use the DAC they invented on several peptides to create long-lasting analogs. GHRH was not something they cared much about. Insulin and a few others are where the money's at... diabetes is big money.

But they attached the DAC to GRF(1-29) and studied it. They needed to add a Lysine amino acid between GRF(1-29) and the DAC as sticky glue. This is the trickiest part to synthesize because most attempts will not take and the yield is low.

So in that human study they needed comparisons. So they attached the DAC to 3 analogs.

The first was simply sticking it onto GRF(1-29) w/ Lysine glue. This they called CJC-1288. The reason they did not call it GRF(1-29) is because they added the Lysine and their patented DAC.

That is precisely why the term CJC was used. Predictably CJC-1288 degraded rather quickly because it had no amino acid swaps to make it stronger. So within minutes there was cleavage at the 2nd position. GRF(1-29) has little to no bioactivity when that occurs.

They then made the swap I have been talking about. They swapped Arginine at the 2nd position for a more resistant D-Arginine. No other swaps were made. They then used the Lysine sticky and attached the DAC.

The Lysine/ DAC seems to confer a little more protection from degradation via stiff arm.

This peptide was named CJC-1293. Note that it is the same peptide discussed above where there is just the one swap. The half-life of that peptide is still below 10 minutes. Adding the DAC made CJC-1293 have a longer half-life.

But if you you remove the DAC or call if CJC-1293 (w/o the DAC) you know what you end up with? You end up with That old analog of GRF(1-29) with Arg swapped for the D form at the 2nd position. It is barely better then GRF(1-29). In fact I was being a bit kind to it by saying less then 10 minutes. The half-life is around 5 minutes.

Then in that same study they took GRF(1-29) and made 4 amino acid substitutions. The one at the 2nd position as just described and 3 more. This made the GRF structure more viable and to that they attached the Lysine glue and the DAC.

This they called CJC-1295.

You know what you get when you take off that Lysine/DAC? You get GRF(1-29) w/ 4 amino acid swaps. This is called tetra-substitued in that study. The term tetra is Greek for four. So it could be called 4-sub. Bob liked the term tetra-sub. But just to **** with him I decided to call it modified. Seriously I don't know why I labeled it that exactly. That has a half-life of a bit more then 30 minutes.

Now adding the DAC gives Modified GRF(1-29) and also the analog w/ just the 2nd amino acid a longer half life. The DAC on Modified GRF(1-29) gives it a half-life of half a week. But having a GHRH always around means the GHRH-receptors just leak GH all the time. That is what I mean by GH bleed.

There is some good speculation that CJC-1295 could cause pituitary problems because of the chronic bleed. I looked at this pretty hard and even wrote something on it. I have the opinion that lower doses will not present such a problem but the higher doses used in the study make me back off my opinion. I advised taking a break if you did run genuine CJC-1295 at those study doses. I believe in the well respected JAMA (Journal of the American Medical Association) concern was expressed over CJC-1295 as an open ended question.

So how and why does it come to pass that a retailer labels GRF(1-29) w/ one amino swap and a piss poor half-life as CJC-1293...then goes on and states that THAT is the technical term for something with 4 amino acid swaps? I shouldn't tell on myself. Well you know how I am prone to go off on a tangent sometimes? Well once on "the private board with no name" I whipped off such a post and made the statement that CJC-1293 was Modified GRF(1-29). It sat there for maybe a month and when I revisited it I had to laugh at my mistake and of course I deleted it (so noone would know ****can make a mistake).

SO I am not saying that a retailer just took from me and then pretends such a thing springs from his own genius. It is entirely possible that I am not the only idiot. But seriously what are the odds... right?

Bottom line though is if you have CJC-1293 w/o the DAC you have a peptide inferior to modified GRF(1-29). But who really knows what you have? Stenlabs use to sell Gaba/Gabob as MGF. 




Growth Hormone Releasing Hormone (GHRH) aka GRF(1-44) (Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH2) = half-life "less then 10 minutes", perhaps as low as 5 minutes. - Ref-2


- GRF(1-29) aka Sermorelin (Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2) - the biologically active portion of the 44 amino acid GHRH = half-life "less then 10 minutes", perhaps as low as 5 minutes. - Ref-3


GHRH 

Now Sermorelin, GHRH (1-44) and GRF(1-29) all are basically GHRH and have a short half-life in plasma because of quick cleavage between the 2nd & 3rd amino acid. This is no worry naturally because this hormone is secreted from the hypothalamus and travels a short distance to the underlying anterior pituitary and is not really subject to enzymatic cleavage. The release from the hypothalamus and binding to somatotrophs (pituitary cells) happens quickly.

However when injected into the body it must circulate before finding its way to the pituitary and so within 3 minutes it is already being degraded.

That is why GHRH in the above forms must be dosed high to get an effect.

GHRH analogs 

All GHRH analogs swap Alanine at the 2nd position for D-Alanine which makes the peptide resistant to quick cleavage at that position. This means analogs will be more effective when injected at smaller dosing.

The analog tetra or 4 substituted GRF(1-29) sometimes called CJC w/o the DAC or referred to by me as modified GRF(1-29) has other amino acid modifications. They are a glutamine (Gln or Q) at the 8-position, alanine (Ala or A) at the 15-position, and a leucine (Leu or L) at the 27-position.

The alanine at the 8th position enhances bioavailability but the other two amino substitutions are made to enhance the manufacturing process (i.e. create manufacturing stability).

For use in vivo, in humans, the GHRH analog known as CJC w/o the DAC or tetra (4) substituted GRF(1-29) or modified GRF(1-29) is a very effective peptide with a half-life probably 30+ minutes.

That is long enough to be completely effective.

The saturation dose is also defined as 100mcg.

Problem w/ Using any GHRH alone 

The problem with using a GHRH even the stronger analogs is that they are only highly effective when somatostatin is low (the GH inhibiting hormone). So if you unluckily administer in a trough (or when a GH pulse is not naturally occurring) you will add very little GH release. If however you luckily administer during a rising wave or GH pulse (somatostatin will not be active at this point) you will add to GH release.


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## gymrat827 (Dec 17, 2011)

GHRH difference summary 


I should have said GHRH and its different analogs. Sorry. Proudly stolen from you know who:

GHRH - Growth Hormone Releasing Hormone - 44 amino acid chain as produced in the body (hypothalamus). Half life of minutes.

GRF (1-29) - Growth hormone Releasing Factor created by removing 15 useless (not necessary for GH release) amino acids from GHRH (44 -15 == 29). Still has half life of minutes. Commerically available as Sermorelin.
The analog is GRF (1-29) + DAC == CJC-1288 - still degrades within minutes. 

CJC-1293 w/o DAC - single amino substituted GRF (1 -29). Half life of between 5-10 minutes.
The analog is CJC-1293 with DAC attached extending the half life but causing GH bleed. 

modGRF (1-29) & CJC-1295 w/o DAC - Tetrasub GRF (1-29) with 4 amino acid subs - half life of 30 minutes. 
The analog is CJC-1295 with DAC attached extending the half life to days but causing GH bleed.

Analog - Created by swapping an amino acid(or acids) but still have the same effects as the original compound.
GH Bleed - GHRH Receptors in the pituitary constantly leaking GH due to the presence of GHRH (real or analog), without being inhibited.
DAC - Drug Affinity Complex originally created and patented by Conjuchem. Attaches to a peptide via Lysine to extend half life by binding to albumin. Albumin lasts long in the human body (t 1/2 = 19 days), so anything bound to it will stick around as well. . Attaching DAC via Lysine is the tricky part, and the yield tends to be low, thus the additional cost.


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