Ipamorelin peptide

The ipamorelin peptide, residue by residue

Five residues, written Aib-His-D-2-Nal-D-Phe-Lys-NH2: aminoisobutyric acid, histidine, D-2-naphthylalanine, D-phenylalanine and lysine, with the C-terminus carried as an amide rather than a free acid. The molecular formula is C38H49N9O5 and the molecular weight 711.85 g/mol. It is registered under CAS 170851-70-4.

Aminoisobutyric acid, D-2-naphthylalanine and D-phenylalanine would never appear in a protein. That is the single most useful thing to know about the ipamorelin peptide, and it is legible in the sequence before any pharmacology is discussed. Aminoisobutyric acid is not one of the residues the genetic code specifies. D-2-naphthylalanine and D-phenylalanine are mirror images of the L-forms every ribosome builds with. A chain containing them cannot have been cut out of a larger natural protein.

That separates it from most of the compounds it is listed beside. BPC-157 corresponds to a stretch of a protein found in gastric juice. TB-500 corresponds to a region of thymosin beta-4. The GHK-Cu copper peptide corresponds to three residues of collagen, carrying a copper(II) ion. Sermorelin is the first 29 residues of growth-hormone-releasing hormone. The ipamorelin peptide corresponds to nothing. It is a pentapeptide assembled from building blocks chosen for what they do to the molecule's shape and stability, which is the distinction the tesamorelin vs sermorelin vs ipamorelin comparison turns on.

Ipamorelin peptide registry identifiers, and which figures a supplier can vary

A name is not an identifier. The ipamorelin peptide is spelled several ways in circulation, appears under at least two supplier code numbers, and is grouped by name with molecules it has no structural relationship to. CAS 170851-70-4 is none of those things. When a certificate, a catalogue entry and a literature citation have to be matched up as describing one substance, the registry numbers are what does the matching.

The table below is the whole identity block in one object. The distinction worth holding onto while reading it is which figures a supplier can vary and which it cannot. Sequence, formula, mass, CAS number and the registry identifiers are properties of the molecule and are identical wherever it is bought. Purity, net peptide content and lot number are properties of one batch, and differ from vial to vial.

The InChIKey is given as its first block only. That block is a hash of the molecular skeleton, connectivity without stereochemistry, so on its own it matches any stereoisomer of the same constitution, including the all-L version that does not exist. The full 27-character key, which encodes the D-configurations too, is on the PubChem record.

Why a designed peptide is built this way

Proteases are stereospecific. The enzymes that cut peptide bonds evolved against substrates made of L-amino acids, and their active sites read the geometry around the alpha carbon as part of recognising where to cut. Substitute a D residue and that geometry is inverted. The bond is chemically the same bond, but the enzyme no longer fits it, and D residues inside a five-residue chain leave very little for a standard protease to recognise.

Aib works by a different route. Its alpha carbon is quaternary: fully substituted, where a normal residue has one substituent and a hydrogen. That makes it both sterically obstructive and conformationally restrictive. It narrows the range of backbone angles the chain can adopt at that position and presents an awkward shape to anything trying to bind the backbone there. Placing it first puts that obstruction exactly where an aminopeptidase would begin.

The amide at the other end closes the same argument from the opposite direction. A free C-terminal carboxylate is ionised at physiological pH and is part of what carboxypeptidases recognise. Capping it as -NH2 removes the charge and the recognition feature together. Between the N-terminal Aib, the D residues in the middle and the amide at the tail, the chain offers no conventional point of attack along its length.

None of that is incidental. A short chain of ordinary L-residues with free termini is a fragile object in any biological matrix, and the three modifications in this sequence are the standard toolkit for making a short peptide durable enough to study. They are also, taken together, the reason its structure looks nothing like a natural fragment.

Where the sequence came from: GHRP-1 and the secretagogue series

It did not appear from nowhere. The ipamorelin peptide was characterised at Novo Nordisk and reported in 1998 as the first selective growth hormone secretagogue of its class, and it was built out of a series that already existed. A supplier page currently ranking for this term describes it as derived from GHRP-1, and the two sequences read as a deliberate edit rather than a coincidence.

As those sequences are conventionally written, GHRP-1 is Ala-His-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2 and ipamorelin is Aib-His-D-2-Nal-D-Phe-Lys-NH2. Line them up and three changes account for the whole difference: the N-terminal alanine becomes aminoisobutyric acid, the central Ala-Trp pair is deleted, and everything else carries over unchanged, meaning His, D-2-Nal, D-Phe and the amidated lysine.

What carries over is the part worth noticing. The -D-Phe-Lys-NH2 tail appears in compound after compound in this series. GHRP-2, also called pralmorelin, is D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2. GHRP-6 is His-D-Trp-Ala-Trp-D-Phe-Lys-NH2. Hexarelin is His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2. All six or seven residues, all ending the same way. The class is a set of variations on one recognition motif, shortened and substituted in different directions, and the ipamorelin peptide is the shortest member of it.

Two of the three edits are the durability modifications described above. The third, the deletion, is the interesting one: dropping Ala-Trp takes the chain from seven residues to five without touching the motif at the C-terminal end.

How the ipamorelin peptide is assembled

By solid-phase synthesis, in the same deprotect-couple-wash cycle used for any short peptide, but with two decisions taken at the start. The first is the resin. A C-terminal amide is not added afterwards; it is built in by anchoring the first residue to a resin whose linker releases the finished chain as a carboxamide rather than as a free acid. The -NH2 in Aib-His-D-2-Nal-D-Phe-Lys-NH2 is a property of the support the chain grew on.

The second is the non-standard residues, which are bought as protected building blocks like any other and coupled the same way. The D-amino acids present no particular difficulty, because the chemistry is indifferent to handedness. Aib is harder. Coupling onto a hindered quaternary alpha carbon is slower and less complete than coupling onto a normal residue, and that step is the one most likely to leave a deletion sequence behind if it is rushed.

At five residues this is still a short synthesis, and short syntheses are forgiving, which is why purity figures at this end of the category sit so consistently high. The chain is then cleaved from the resin, purified by preparative HPLC, which is where the trifluoroacetate counter-ion usually enters, and freeze-dried to the white cake of lyophilized powder that goes into the vial.

The counter-ion deserves a sentence of its own, because it is the quiet reason two correctly labelled vials can hold different amounts of peptide. Preparative HPLC is normally run with trifluoroacetic acid in the mobile phase, and the basic side chains in this molecule, the lysine and the histidine, come off the column paired with trifluoroacetate. What is freeze-dried is a trifluoroacetate salt rather than the free peptide, and that counter-ion is part of the mass in the vial.

How much of it depends on the batch. A salt exchange to acetate can be run afterwards where a study needs it, and some material is supplied as an acetate salt for that reason. Either way the label mass, 5mg or 10mg, is a fill weight, and the ipamorelin peptide itself is a fraction of it. That fraction is the net peptide content, and it is the figure most certificates for this compound do not report at all.

A secretagogue, not a GHRH analogue, and where CJC-1295 sits

Ipamorelin acts at GHS-R1a, the ghrelin receptor. Tesamorelin and sermorelin act at the growth-hormone-releasing hormone receptor. Those are two different receptors, and that is the whole reason the ipamorelin peptide is classed as a growth-hormone secretagogue while the other two are classed as GHRH analogues.

The names hide it. Three compounds ending in -relin, all associated with the growth-hormone axis, read as three versions of one idea, and they appear together constantly. The sequences do not support the reading. Sermorelin is GRF(1-29)NH2, the first 29 residues of a natural hormone, roughly 3358 g/mol, included here as the reference point and not stocked. The ipamorelin peptide is five residues and 711.85 g/mol, and includes residues no hormone could supply.

The compound that belongs in this comparison and is usually missing from ours is CJC-1295. It is the term most often searched alongside this one, and it sits squarely on the GHRH side of the line. CJC-1295 is built on the same 29-residue GHRH backbone sermorelin uses, with four substitutions that slow enzymatic cleavage and, in the DAC form, a C-terminal lysine carrying a maleimide linker. The linker is the point of that molecule: it forms a covalent bond to serum albumin, and published figures put the circulating half-life of the DAC form in days where the unmodified fragment is measured in minutes.

Structurally the two have nothing in common. One is a chain derived from a human hormone and modified to survive; the other is five residues of which three could not occur in a hormone at all, and they bind different receptors. That is the comparison this page makes, and the only one it makes: nothing here describes combining them, or using either.

Structure and classification agree, which is the point. A truncated natural hormone binds the natural hormone's receptor. A designed pentapeptide built around a bulky aromatic D residue binds a different one. Where these names appear in the same sentence, it is the receptor and not the suffix that decides which column each belongs in. Tesamorelin is stocked here and sits in the other column from the ipamorelin peptide for exactly that reason; the tesamorelin peptide profile sets out its 44-residue sequence in the same form as this page sets out five.

The published half-life, and what it measures

One figure recurs in every reference summary of this molecule: an elimination half-life of about two hours. It comes from Gobburu, Agerso, Jusko and Ynddal, "Pharmacokinetic-pharmacodynamic modeling of ipamorelin", Pharmaceutical Research 1999, volume 16 issue 9, pages 1412 to 1416, PMID 10496658.

It is worth being precise about what that figure is. A half-life is the time a concentration takes to fall by half in a compartment, fitted from a concentration-time curve. It is a parameter of a model, not a property of a vial, and it describes persistence rather than activity. It is reported here because after the molecular weight it is the best-established published number about this compound, and because a page that omits it is less informative than the encyclopaedia entry ranking above it on 389 words.

Against its own class it is a long figure, and the reason is already on this page. The hexapeptides in the GHRP series are short-lived. The DAC form of CJC-1295 is very long-lived, deliberately so. The ipamorelin peptide sits between them without any albumin-binding machinery, on the strength of three structural modifications: Aib at the N-terminus, D-residues in the middle, an amide at the tail.

What the preclinical literature studies

The study points that recur are few, and each of them is a property of a model system rather than a statement about people.

The first is selective agonism at GHS-R1a itself, and the growth-hormone-release signalling that follows from it in preclinical models. Blocking experiments in the 1998 characterisation placed the effect at that specific receptor rather than a general one, which is what licenses the receptor assignment in the table above. The second is the shape of that signalling over time: pulsatile GH-release patterns in rodent models, studied as a pattern rather than a quantity.

The third is selectivity, and it is usually stated too narrowly. The 1998 work reported growth hormone rising without a meaningful rise in cortisol, ACTH or prolactin, which is three endpoints rather than one, and supplier characterisations of the same compound extend the panel to FSH, LH and TSH. The comparison that gives any of it meaning is against the earlier hexapeptides in the same series, which do raise ACTH and cortisol in the same assays. Selectivity here is a statement about measured endpoints in a defined panel, and it is comparative: the sentence is always "relative to GHRP-2 and GHRP-6", and it means nothing without them.

All of that is preclinical, and all of it is described as model systems because that is what it is. The ipamorelin peptide is supplied for in-vitro laboratory research only, and nothing on this page describes what it does in a person.

Regulatory status, stated plainly

Six of the eight measurable pages ranking for this term mention the FDA. Stating the position is worth doing, because it is the fact that explains why this page is written the way it is.

In October 2023 the FDA placed ipamorelin, along with CJC-1295, in Category 2 of its evaluation of bulk drug substances nominated for use in compounding under section 503A of the Federal Food, Drug and Cosmetic Act. Category 2 is the category for substances the agency identified significant safety risks with, or for which it found the supporting information insufficient. A Category 2 substance is one the agency has declined to put on the list compounders may use.

The second point is about how pages in this category are read. Enforcement turns on the site as a whole rather than on any single sentence: outcome claims, dosing guidance, references to named conditions and anything amounting to instructions for preparing a dose are read together as evidence of intended use, and a research-use disclaimer at the foot of the page does not offset them.

That is the reason for the shape of this article. Everything on this ipamorelin peptide page is a property of the molecule, of the synthesis, of the container or of the certificate. Ipamorelin is supplied for in-vitro laboratory research only, and there is nothing here addressed to a reader who is taking it, because there is no such reader. How to vet a research peptide supplier sets out what a supplier in this category should be publishing instead.

How the ipamorelin peptide is supplied, stored and handled

A white lyophilised cake, also spelled lyophilized, soluble in bacteriostatic water, stored at −20°C for the long term and protected from light. The ipamorelin peptide is stocked in 5mg and 10mg vials, released at 99.90% purity by HPLC.

That is the specification in one line. The table below sets it out per state, with the figures published specifications for the same compound add, marked as theirs rather than ours.

Two rows deserve drawing out. The first is the room-temperature tolerance. A published supplier specification gives three weeks at ambient temperature for the lyophilised powder, which is a shipping tolerance rather than a storage instruction; it is the reason a vial that has spent four days in transit is not compromised, and the reason cold-chain shipping is not the differentiator it is sometimes presented as. The second is the carrier protein. For material held in solution over a long period, 0.1% human or bovine serum albumin is a conventional addition to a research preparation, because a peptide at low concentration adsorbs onto glass and plastic and disappears from solution without ever degrading. The same specifications give not less than 100 micrograms per millilitre as the concentration to reconstitute to, for the same reason.

Freeze-thaw is the failure mode worth the most attention, because it is the one that leaves no trace. Each cycle concentrates solutes at the advancing ice front and drags the ipamorelin peptide across a moving interface, the damage accumulates, and the solution looks identical afterwards. Aliquot once, at the point of reconstitution, rather than returning a single vial to the freezer repeatedly. How to store peptides covers the reasoning in more detail.

Errors in circulation about the ipamorelin peptide

The ipamorelin peptide is mis-described unusually often, and the errors sit in checkable fields rather than in the prose around them. Three of the ones below are on pages currently ranking for this term.

The residue count is wrong in both directions. A supplier product page in the current top five states four amino acids in the same paragraph as the correct formula and the correct mass. Other published summaries state nine. The written sequence has five residues in it, and C38H49N9O5 at 711.85 g/mol is what those five weigh; neither four nor nine is consistent with the formula those same pages print. Count the sequence, not the summary field.

The classification error matters more, because it puts the molecule at the wrong receptor and therefore in the wrong half of every comparison it appears in. It comes from the names: a page that groups the -relin compounds together by suffix has already made it before writing a word about structure.

Lot by lot: what each certificate reports

For a peptide this short, purity is the weaker number on a certificate. Identity is stronger, and net peptide content is the figure most often absent altogether.

Three lots of the ipamorelin peptide have been released and all three certificates are published. Their purity figures run from 99.657% to 99.984%, which is a narrow band and about what a five-residue synthesis should deliver. Their net peptide contents run from 9.36mg to 13.12mg on a 10mg fill, which is not a narrow band at all.

Both statements describe the same three vials, and the second is the more informative one. Net peptide content is the mass of peptide itself once trifluoroacetate and residual water are set aside. A 10mg fill at 9.36mg net and a 10mg fill at 13.12mg net are both within specification and both correctly labelled; they carry different amounts of salt and water, which is a property of the batch and not of the label. Purity says what fraction of the material is the right molecule. Net peptide content says how much of it there is. A certificate reporting one without the other has answered half the question.

Set that against what else is published for this compound. One supplier states greater than 97.0% by RP-HPLC; another states 99% or better by HPLC and mass spectrometry. Both are claims about a product line. Neither publishes a figure against a lot number, and neither reports net peptide content at all. Peptide purity testing covers why a percentage without a method and a lot number is not a measurement, and peptide purity sets out what the percentage measures in the first place.

That is the argument for assaying every batch instead of publishing one certificate and reusing it. A certificate that does not name the lot printed on the vial describes somebody else's batch, which is why each one here is published against its lot number in the certificate of analysis library.