MGF (Mechano Growth Factor) Research, Specifications & Scientific Information

MGF, or mechano growth factor, is a 24-residue synthetic peptide corresponding to the C-terminal E domain of IGF-1Ec, an alternatively spliced transcript of the insulin-like growth factor 1 gene. It has never been studied in a clinical trial, its receptor has never been identified, and its central in vitro findings failed to replicate at two pharmaceutical companies in 2014. It is not approved by the FDA for any indication.

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Category: IGF and growth-factor peptides

Introduction

MGF is the most contested compound in this library, and the contest is worth setting out before anything else.

In 1996 a group at the Royal Free in London cloned an insulin-like growth factor 1 transcript that appeared in rabbit tissue subjected to stretch and was essentially absent from resting tissue. A 52-base-pair insert shifted the reading frame and produced a different C-terminal E domain, giving an isoform they named IGF-1Eb in rodents and IGF-1Ec in humans [1]. Because the transcript responded to mechanical loading, the isoform acquired the name mechano growth factor.

From there the story splits in two. One branch concerns the transcript, and it is well supported: the splice variant rises sharply after local tissue damage in rats and declines within days, in a sequence that tracks satellite cell activation markers [4]. The other branch concerns a 24-residue synthetic peptide corresponding to the end of that E domain, sold under the same name. That branch is where the disagreement lives. The peptide's reported activities were published between 2002 and 2011; in 2014 a team drawn from two pharmaceutical companies tested the same endpoints and found nothing [9].

This page describes research, and it reports both branches. It does not describe use in people or animals, and it contains no guidance of any kind on handling the material.

What Is MGF?

Two different things are called MGF, and conflating them is the commonest error in writing about this compound.

The splice variant. IGF-1Ec in humans, IGF-1Eb in rodents: an alternatively spliced transcript of the IGF1 gene across exons 4, 5 and 6, carrying a 49-base-pair insert in humans and 52 in rodents that shifts the reading frame of the derived carboxyl terminus [1, 8]. This is a real, measurable transcript whose expression has been quantified in rabbits, rats and humans.

The synthetic peptide. A 24-residue chain, YQPPSTNKNTKSQRRKGSTFEERK, corresponding to the C-terminal residues of that alternative E domain. This is what is supplied as MGF and it is what the FDA/NCATS register carries under UNII Q86M4KXC2P.

The relationship between the two is exactly the question. A 2010 review in Endocrinology stated the position without hedging: no analogous peptide product of the IGF1 gene has been identified in or isolated from cultured cells, their conditioned medium, or in vivo animal tissues or biological fluids [6]. The transcript is observed; the free peptide it would have to be cleaved from has not been.

It is not an approved medicine anywhere, it has not been the subject of any clinical trial, and it has never been developed as a candidate for one.

MGF Specifications

Compound name
MGF (mechano growth factor)
Full chemical name
Insulin-like growth factor 1-Ec peptide, C-terminal 24-residue E domain
Aliases
mechano growth factor, IGF-1Ec, IGF-1 Ec peptide, MGF-24aa-E peptide, MGF-Ct24E, IGF-1Eb (rodent orthologue)
Development code
Not publicly characterised
CAS number
Not publicly characterised
PubChem CID
Not publicly characterised
UNII
Q86M4KXC2P
Compound type
Synthetic peptide corresponding to a splice-variant-derived E domain
Peptide family
Insulin-like growth factor family, E-domain peptides
Amino acid sequence
YQPPSTNKNTKSQRRKGSTFEERK
Sequence length
24 residues
Molecular formula
Not publicly characterised
Molecular weight
2868.17 g/mol (register calculated value)
Primary target
Not established. The original reports concluded the peptide acts through a receptor other than the type 1 IGF receptor, and no receptor has been identified.
Secondary targets
Not publicly characterised
Receptor family
Not publicly characterised
Agonist / antagonist status
Not established

The 24-residue chain above is the sequence recorded in the FDA/NCATS Global Substance Registration System under UNII Q86M4KXC2P, where the substance is named mechano growth factor, MGF, IGF-1-EC and insulin-like growth factor 1-Ec peptide. The register publishes a calculated average mass of 2868.17 g/mol, carries no CAS registry number for the substance, and publishes no molecular formula; no PubChem compound identifier resolves for the name, so those three fields are shown as unknown rather than estimated. A second register record, UNII Y65LH7J9BL, carries the same 24-residue chain with a C-terminal amide and is a distinct substance from the free-acid form above. What the register does not settle, and what the literature disputes, is whether this peptide is ever produced as a free species in living tissue: it corresponds to the C-terminal portion of an alternatively spliced pro-insulin-like growth factor 1 precursor, and a 2010 review in Endocrinology recorded that no analogous peptide product of the IGF1 gene had been identified in or isolated from cultured cells, their conditioned medium, or animal tissues or biological fluids.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does MGF Work?

The honest answer is that nobody has established how, or whether, it works.

The original proposal was specific and testable. The E domain of the splice variant was reported to act differently from mature insulin-like growth factor 1 — increasing proliferation of myoblasts while delaying their terminal differentiation, where the mature growth factor promotes differentiation. Blocking the type 1 IGF receptor with a specific antibody did not abolish the E domain's activity, which led the authors to conclude that it signals through a different receptor [3].

That conclusion has a consequence that is easy to skip past: a compound whose activity is defined by not using the obvious receptor has, by construction, no identified receptor at all. Three decades after the transcript was cloned, none has been reported. The specification table on this page shows the primary target as not established, and that is a statement about the literature rather than about the completeness of this page.

The transcript-level account is better supported and is a separate claim. After mechanical damage in rat tibialis anterior, the splice variant was rapidly expressed and declined within a few days, while the systemic IGF-1Ea variant rose more slowly, its increase matching the decline of the first. Satellite cell activation markers — M-cadherin and MyoD — peaked before the IGF-1Ea transcript, which led the authors to propose that the initial pulse of the splice variant is what activates satellite cells, with the later switch toward IGF-1Ea supplying mature growth factor for protein synthesis [4]. That is a model about transcript timing. It is not evidence that an administered 24-residue peptide does anything.

MGF Mechanism of Action

In vitro research

The cell-culture record divides cleanly into two sets of results that do not agree.

What the original reports found

In C2C12 myoblasts, the distinct E domain of the splice variant inhibited terminal differentiation while increasing proliferation, unlike mature insulin-like growth factor 1. Antibody blockade of the type 1 IGF receptor indicated to the authors that the E domain's function is mediated by a different receptor [3].

A separate group reported a pro-migratory activity for the same synthetic 24-residue peptide on human myogenic precursor cells, both in culture and after transplantation. The peptide enhanced expression of urokinase plasminogen activator, its receptor and matrix metalloproteinase 7 while reducing plasminogen activator inhibitor 1 activity, and had no effect on gelatinases MMP-2 and MMP-9. Those authors also reported results suggesting the responses did not involve the type 1 IGF receptor [5].

Work on primary human satellite cells from donors of different ages reported that the 24-residue peptide increased proliferative lifespan and delayed senescence in cells from neonatal and young adult donors, but not in cells from old adult donors [8]. Structure-function work in C2C12 cells has continued in the same tradition [11].

What the replication attempt found

In 2014, investigators at two pharmaceutical companies set out to reproduce the central claims. Concentrations of the peptide up to 500 ng/mL failed to increase proliferation of C2C12 cells or of primary human skeletal myoblasts. The peptide failed to inhibit differentiation of myoblasts into myotubes. Primary mouse skeletal stem cells, used to test whether responsiveness had been lost in immortalised lines, showed no significant effect either. A documented signalling readout — activation of phosphorylated ERK but not phosphorylated Akt in cardiac myocytes — produced no activating response from either the native or a stabilised version of the peptide. In every one of those experiments, mature insulin-like growth factor 1 or full-length IGF-1Eb produced a robust response, which is what establishes that the assays were working [9].

The authors' closing sentence is that these results call into question whether there is a physiological role for MGF at all.

How this page treats that

It reports both, and it does not adjudicate between them. What it will not do is present the 2002–2011 findings as settled, because a well-powered negative replication with working positive controls is not a minor footnote to a literature — it is part of it.

What Is MGF Being Researched For?

Four lines are identifiable in the published record, and they are unequal in weight.

  • Splice-variant biology. The best-supported line. Expression of IGF-1Ec and IGF-1Ea transcripts after mechanical loading, damage and exercise, in rabbits, rats and humans [1, 2, 4, 10, 7].
  • Satellite cell activation. Whether the transcript pulse is what activates satellite cells, studied at the level of transcript timing in rodents rather than by administering a peptide [4].
  • In vitro activity of the 24-residue peptide. Proliferation, differentiation and migration endpoints, with the contradictory record described above [3, 5, 8, 9].
  • Neural progenitor biology in rodents. Genetic overexpression of the splice variant in mice, not administration of the peptide [12].

There is no clinical trial of MGF in any indication, no registered programme, and no approval. Where the word "human" appears in this literature it almost always refers either to human cells in culture or to transcript measurements in biopsy samples.

Human Expression Data on MGF

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

The human data in this literature are observational measurements of endogenous transcripts, not studies of an administered compound, and that distinction is the reason this section is short.

The original cloning paper already included a human component: oligonucleotide primers were designed to amplify both isoform cDNAs in humans as well as rabbits, and appreciable levels of the IGF-1Ec isoform were detected in skeletal musculature following altered physical activity lasting from two hours to six days, where very little was detectable in unstretched control tissue [1].

Later work extended that to age comparisons. Transcript expression patterns for the insulin-like growth factor 1 splice variants were profiled in young and old adults before and after sequential bouts of exercise [7], and the effects of a resistance training programme on splice-variant expression were compared between younger and older men [10].

What none of this establishes is anything about the synthetic peptide. These studies measure how a gene is spliced in living tissue under load. They do not administer MGF, they do not measure a free E-domain peptide, and they cannot speak to what happens when a 24-residue chain is introduced from outside.

Preclinical Research on MGF

Animal research

The animal literature is likewise mostly about the transcript rather than the peptide.

The founding experiment was in rabbits. Total RNA from tissue induced to undergo rapid hypertrophy by active stretch was compared with control tissue by Northern hybridisation and by reverse transcription polymerase chain reaction. Resting tissue yielded a single isoform, IGF-1Ea. Stretched tissue yielded an additional isoform whose E-domain sequence differed by a 52-base-pair insert, changing the reading frame of the derived carboxyl terminus [1]. Related work characterised the accompanying changes in mass, phenotype and autocrine and systemic growth factor expression under stretch and overload [2].

The rat time-course study is the most informative single animal experiment in this literature. Transcripts were measured by real-time reverse transcription polymerase chain reaction in tibialis anterior at intervals after two different kinds of local damage — mechanical damage from electrical stimulation of stretched tissue, and chemical damage from bupivacaine injection. Both produced the same pattern: rapid expression of the splice variant followed by decline within days, with the slower IGF-1Ea rise matching that decline. Satellite cell activation markers peaked between the two [4].

Two features of that design are worth naming. It used two mechanistically unrelated forms of damage and obtained the same transcript sequence, which is a genuine internal control. And it measured markers of the process it wanted to explain rather than assuming them.

Findings described in this section were observed in animals, and nothing in them establishes anything about humans.

Other Areas of MGF Research

Animal research

A line of work outside the musculoskeletal field concerns the brain, and it is instructive about what the evidence actually covers.

In control mice, endogenous expression of the splice variant was found in neurogenic areas of the brain and declined with age. Transgenic mice constitutively overexpressing it from birth showed significantly increased numbers of proliferating cells in the dentate gyrus and the subventricular zone, though the distribution of neurons at post-mitotic maturation stages was unchanged. Using a conditional system, overexpression begun at one and three months of age produced increases in proliferating and differentiated mature neurons in the olfactory bulbs at twenty-four months, with preserved olfactory function; overexpression begun at twelve months did not. In culture, neurospheres from subventricular-zone-derived neural stem cells increased in size and number [12].

The method there is genetic overexpression of a splice variant, not administration of a 24-residue peptide. That is a different intervention testing a different claim, and it should not be cited as evidence for what the peptide does.

Findings described in this section were observed in animals.

Current Research Status

Regulatory status (United States)
Not approved. This peptide has not been approved by the U.S. Food and Drug Administration for any indication, and no product containing it is known to have been submitted for approval.
Investigational status
No clinical trial of the synthetic peptide has been identified in public trial registers or in the peer-reviewed literature. Human data concern endogenous expression of the corresponding splice transcript measured in biopsy samples, not administration of the peptide. The cell-culture literature is divided: the original reports of proliferative and pro-migratory activity were followed in 2014 by a multi-laboratory attempt at replication, conducted at two pharmaceutical companies, that found no effect.
Highest research phase reached
No clinical study of the peptide identified; in vitro and animal research only, with published failure to replicate the central in vitro findings
Approved uses
None
Approval is compound-specific
No

Status as of . This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Chemical & Molecular Characteristics

The sequence is a register record. YQPPSTNKNTKSQRRKGSTFEERK is the 24-residue chain carried under UNII Q86M4KXC2P, where the substance is named mechano growth factor, MGF, IGF-1-EC and insulin-like growth factor 1-Ec peptide. The register publishes a calculated average mass of 2868.17 g/mol.

There are two register entries, not one. UNII Y65LH7J9BL carries the same chain with a C-terminal amide, recorded as a structural modification at the terminal lysine. An amidated peptide and a free-acid peptide are different substances with different masses, and material supplied under the bare name MGF may be either. The certificate of analysis for a given lot is the record for that lot.

Three fields are blank on purpose. The register carries no CAS registry number and no molecular formula for this substance, and no PubChem compound identifier resolves for the name. All three are shown as unknown rather than estimated.

The sequence is predicted, not purified. This is the point that distinguishes MGF from most entries in this library. The 24 residues correspond to the C-terminal portion of a translated open reading frame inferred from a splice variant. The peptide itself has not been isolated from tissue, conditioned medium or biological fluid [6]. A register record establishes what the substance supplied is; it does not establish that the same species occurs in an organism.

Frequently Asked Questions

What is MGF?
MGF, short for mechano growth factor, is a 24-residue synthetic peptide with the sequence YQPPSTNKNTKSQRRKGSTFEERK. It corresponds to the C-terminal portion of the E domain of IGF-1Ec, an alternatively spliced transcript of the insulin-like growth factor 1 gene that was cloned in 1996 from stretched rabbit tissue [1]. The FDA/NCATS register carries it under UNII Q86M4KXC2P.
How is MGF related to IGF-1?
They come from the same gene and are not the same molecule. The IGF1 gene can be spliced across exons 4, 5 and 6 in more than one way. One product, IGF-1Ea, yields the familiar mature insulin-like growth factor 1. Another, named IGF-1Eb in rodents and IGF-1Ec in humans, carries an insert that shifts the reading frame and produces a different C-terminal E domain [1]. The synthetic peptide sold as MGF is the last 24 residues of that alternative E domain, not the mature growth factor and not a fragment of it [6].
How does MGF work?
That is genuinely unsettled. The original in vitro report found that the E domain increased myoblast proliferation and delayed terminal differentiation, and that blocking the type 1 IGF receptor with a specific antibody did not abolish the effect, from which the authors inferred a different and unidentified receptor [3]. No such receptor has since been identified. A 2014 study at two pharmaceutical companies failed to reproduce those effects at concentrations up to 500 ng/mL in several cell systems [9]. This page states the mechanism as not established, because that is what the literature supports.
Is MGF FDA approved?
No. This peptide has not been approved by the U.S. Food and Drug Administration for any indication, and no product containing it is known to have been submitted for approval.
Has MGF been studied in humans?
The peptide has not. No clinical trial of administered MGF has been identified in public trial registers or in the peer-reviewed literature. What human data exist are observational measurements of the endogenous IGF-1Ec transcript in biopsy samples, for example across age groups and after bouts of exercise [10, 7]. Measuring a transcript in tissue is a different kind of evidence from administering a peptide, and the two should not be conflated.
Does MGF exist naturally as a free peptide?
The transcript certainly exists; the free peptide is unproven. A 2010 review in Endocrinology set this out directly: no peptide product of the IGF1 gene corresponding to the synthetic MGF sequence has been identified in or isolated from cultured cells, their conditioned medium, or animal tissues or biological fluids [6]. The synthetic peptide is therefore best described as corresponding to a predicted sequence rather than as a purified natural product.
Why do sources disagree about what MGF does?
Because the primary literature itself disagrees. Between 2002 and 2011 several groups reported that the 24-residue peptide increased myoblast proliferation, delayed differentiation, promoted migration of human myogenic precursor cells and extended the proliferative lifespan of satellite cells from younger donors [3, 5, 8]. In 2014 a team drawn from two pharmaceutical companies tested the same endpoints in C2C12 cells, primary human myoblasts, primary mouse stem cells and cardiac myocytes and found no effect on any of them, while mature insulin-like growth factor 1 produced a robust response in the same experiments [9]. Both bodies of work are in the peer-reviewed record and this page reports both.
What identifiers are published for MGF?
The FDA/NCATS Global Substance Registration System carries the substance under UNII Q86M4KXC2P with the 24-residue sequence and a calculated average mass of 2868.17 g/mol. It carries no CAS registry number and no molecular formula, and no PubChem compound identifier resolves for the name, so those fields are shown as unknown. A separate register entry, UNII Y65LH7J9BL, covers the C-terminally amidated form, which is a different substance.

Scientific References

  1. Yang S, Alnaqeeb M, Simpson H, et al.. Cloning and characterization of an IGF-1 isoform expressed in skeletal muscle subjected to stretch Journal of muscle research and cell motility; 1996. PMID 8884603 doi:10.1007/BF00123364
  2. Goldspink G. Changes in muscle mass and phenotype and the expression of autocrine and systemic growth factors by muscle in response to stretch and overload Journal of anatomy; 1999. PMID 10386770 doi:10.1046/j.1469-7580.1999.19430323.x
  3. Yang SY, Goldspink G. Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation FEBS letters; 2002. PMID 12095637 doi:10.1016/s0014-5793(02)02918-6
  4. Hill M, Goldspink G. Expression and splicing of the insulin-like growth factor gene in rodent muscle is associated with muscle satellite (stem) cell activation following local tissue damage The Journal of physiology; 2003. PMID 12692175 doi:10.1113/jphysiol.2002.035832
  5. Mills P, Lafrenière JF, Benabdallah BF, et al.. A new pro-migratory activity on human myogenic precursor cells for a synthetic peptide within the E domain of the mechano growth factor Experimental cell research; 2007. PMID 17156777 doi:10.1016/j.yexcr.2006.10.032
  6. Matheny RW Jr, Nindl BC, Adamo ML. Minireview: Mechano-growth factor: a putative product of IGF-I gene expression involved in tissue repair and regeneration Endocrinology; 2010. PMID 20130113 doi:10.1210/en.2009-1217
  7. Roberts MD, Dalbo VJ, Sunderland KL, et al.. IGF-1 splice variant and IGF-1 peptide expression patterns in young and old human skeletal muscle prior to and following sequential exercise bouts European journal of applied physiology; 2010. PMID 20668872 doi:10.1007/s00421-010-1588-2
  8. Kandalla PK, Goldspink G, Butler-Browne G, et al.. Mechano Growth Factor E peptide (MGF-E), derived from an isoform of IGF-1, activates human muscle progenitor cells and induces an increase in their fusion potential at different ages Mechanisms of ageing and development; 2011. PMID 21354439 doi:10.1016/j.mad.2011.02.007
  9. Fornaro M, Hinken AC, Needle S, et al.. Mechano-growth factor peptide, the COOH terminus of unprocessed insulin-like growth factor 1, has no apparent effect on myoblasts or primary muscle stem cells American journal of physiology. Endocrinology and metabolism; 2014. PMID 24253050 doi:10.1152/ajpendo.00408.2013
  10. Ahtiainen JP, Hulmi JJ, Lehti M, et al.. Effects of resistance training on expression of IGF-I splice variants in younger and older men European journal of sport science; 2016. PMID 27231807 doi:10.1080/17461391.2016.1185164
  11. Yi Q, Feng J, He L, et al.. The structure-function relationships of insulin-like growth factor 1 Ec in C2C12 cells Cell adhesion & migration; 2018. PMID 28471324 doi:10.1080/19336918.2017.1318240
  12. Tang JJ, Podratz JL, Lange M, et al.. Mechano growth factor, a splice variant of IGF-1, promotes neurogenesis in the aging mouse brain Molecular brain; 2017. PMID 28683812 doi:10.1186/s13041-017-0304-0

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.