MOD GRF 1-29 (CJC-1295 W/O DAC)

Description:

Mod GRF 1-29 is a synthetic growth hormone secretagogue from the growth hormone releasing hormone family. These compounds are based on GHRH, a natural peptide hormone that signals the release of GH from the pituitary gland. GHRH is one of two primary positive regulators of GH secretion in humans, acting together with ghrelin. Both hormones are the subjects of extensive drug development. With GHRH, though it can be synthesized as a drug product, it is not really adequate as a therapeutic agent. It is too short acting. Mod GRF 1-29 is potentially more viable. It is a shortened, modified form of GHRH that is more resistant to enzymatic cleavage. It has a longer half-life, and is a more potent agent for increasing serum GH and IGF-1 levels.

Mod GRF 1-29 is almost identical to CJC-1295 in structure. It differs only by the lack of an attached maleimidoproprionic acid group, also known as Drug Affinity Complex (DAC). DAC temporarily binds CJC-1295 to serum albumin, greatly extending its half-life. This is why Mod GRF 1-29 is also commonly called ‘CJC-1295 without DAC.’It simply lacks this complex. Because of this, Mod GRF 1-29 is much shorter acting. It has a half-life measured in minutes or hours instead of days. Whereas CJC-1295 can be injected weekly, Mod GRF 1-29 is usually injected several times daily. Otherwise, these two are the same drug… the same active peptide. In the fitness community, Mod GRF 129 is used for the support of muscle growth and fat loss, as well as its potential anti-aging properties.

Much of what else can be said of CJC-1295 should hold true for Mod GRF 1-29. Most basically, this is to be considered a ‘selective’ GH secretagogue. It displays a great deal of specificity for growth hormone release, and is unlikely to significantly alter levels of cortisol, prolactin, LH (luteinizing hormone), or TSH (thyroid stimulating hormone). Likewise, significant spillover side effects pertaining to these hormones, which are common to many drugs of the GHRP class that mimic ghrelin, are unlikely with Mod GRF 129. That isn’t to say the Mod GRF 1-29 and CJC-1295 are interchangeable. The short acting nature of Mod GRF 1-29 might make it more useful for fostering acute spikes in GH/IGF-1, when used alongside a similarly short acting GHRP (see: Combination Therapy)

Review of GHRH-Related Compounds:

GHRH: Natural 44-amino-acid peptide hormone that stimulates GH secretion in humans. All GHRH family drugs are based on this.

GRF 1-29: Better known as sermorelin. This is a spliced form of GHRH, consisting of its active 29-amino-acid sequence.

Mod GRE 1-29: This is GRE 1-29 (sermorelin) with four amino acid substitutions. It is also known as a tetrasubstituted GRF 1-29.

CJC-1295: This is Mod GRF 1-29 (tetrasubstituted GRF 1-29) with an added Drug Affinity Complex (DAC) to extend its half-life.

Key Points:

• Very Short Acting.

• Moderate Effect on GH

• No Effect on Cortisol, Prolactin

History:

Mod GRF 1-29 was first described in 2005 by Jette et al.1 This drug is ultimately based on a much earlier discovery about growth hormone releasing hormone (GHRH), namely that its full pharmacological activity is retained in its terminal segment of 29 amino acids.2 This led to the development of numerous truncated analogs. First, the active 29 amino acids of GHRH were synthesized in a compound called GRF 1-29. Today we know it as sermorelin, an approved drug product. Though viable, scientists still struggled with its short halflife, and continued to seek out alternatives.

Jette et al sought to further modify the 29 amino acids that make up sermorelin in ways that might reduce its tendency for cleavage, yet still retain biological activity as a GH secretagogue. A tetrasubstituted derivative called CJC1295 was one of the most promising compounds to result from their work. This is the same peptide Mod GRF 1-29 that is described here, but with an additional Drug Affinity Complex to slow its distribution. Subsequent work on this substance continued as CJC-1295. Documentation on actual Mod GRF 1-29 is hard to come by. Neither form of this peptide is presently an approved drug product, in spite of some favorable early human studies. Its potential future as a pharmaceutical agent, likewise, remains unclear.

Mod GRF 1-29 is on the World Anti-Doping Agency’s (WADA) list of prohibited substances. Methods for detecting the misuse of this compound are available.3

Structural Characteristics:

Mod GRF 1-29 is a tetrasubstituted analog of growth hormone releasing fragment 1-29 (GRF 1-29, sermorelin). Its full structural sequence is: Tyr-D-Ala-Asp-Ala-lle-PheThr-Gln-Ser-Tyr-Arg-LysVal-Leu-Ala-Gln-Leu-Ser-Ala-ArgLys-Leu-Leu-Gln-Asp-lle-Leu-SerArg-NH2. Four substitutions to GRF 1-29 create this new peptide: D-Ala at the 2-position, Gln at the 8-position, Ala at position 15, and Leu at position 27. These modifications reduce this compound’s susceptibility to enzymatic breakdown, and increase its bioactivity.4 5 Still, Mod GRF 1-29 has a short half-life, which usually necessitates administering the drug several times per day for optimal effect.

Warnings:

Mod GRF 1-29 is an unapproved new drug. A thorough understanding of its safety and propensity for side effects in humans is lacking at this time.

Obesity, uncontrolled hypothyroidism, hyperglycemia, or elevated plasma fatty acids may impair the effectiveness of Mod GRF 1-29. This drug should never be used during pregnancy, with cancer, a history of cancer, diabetic retinopathy, sclerosing diseases of the liver or lungs, intracranial hypertension, or uncontrolled diabetes

How Supplied:

This drug is not available as a pharmaceutical product. Standard dosage information is unavailable.

Mod GRF 1-29 can be purchased as a research compound or gray market supplement only. It is typically supplied in multi-dose vials containing 2 mg of dry lyophilized powder. This must be reconstituted with saline or bacteriostatic water before use. All unused portions of this drug should be kept under refrigeration.

Side Effects (General):

Common side effects to Mod GRF 1-29 include flushing, warmth, dizziness, and transient hypotension following injection. Other common side effects include sleepiness, headache, diarrhea, nausea, and abdominal pain. Also frequently reported are adverse effects typically associated with other types of growth hormone therapy, such as water retention (edema), joint pain (arthralgias), carpal tunnel syndrome, and numbness or tingling in the extremities. Note that the incidence of GH-related side effects tends to be lower with GHRP therapy as compared to traditional hGH. This is because GH/IGF-1 release is subject to the limits of endogenous synthesis, and as such the drug is less amenable to overdosing.

Side Effects (Injection site):

The subcutaneous administration of this drug may cause redness, itching, pain, or lumps at the site of injection.

Administration:

Mod GRF 1-29 may be given by subcutaneous injection, intramuscular injection, or IV infusion. The subcutaneous route is most often applied.

This drug has not been approved for use in humans. Prescribing guidelines are unavailable.

Availability:

When used for physique- or performance-enhancing purposes, Mod GRF 1-29 is generally administered at a dosage of 50-100 mcg. This is given 1-3 times per day. If single episode dosing is preferred, this is taken before sleep. Day dose(s) are taken on an empty stomach, 3060 minutes before feeding. This is to preserve optimal GH release, as elevated plasma fatty acids and/or glucose may blunt the GH elevating effects of Mod GRF 1-29. Total daily dosage generally does not exceed 300 mcg.

Cycles of Mod GRF 1-29 usually last 3-4 months, though programs of 6 months or longer are not uncommon.

Combination Therapy:

Mod GRF 1-29 (a GHRH family drug) is usually combined with a drug from the GHRP (Growth Hormone Releasing Peptides) class, such as such as GHRP-2, GHRP-6, hexarelin, ipamorelin, or MK-677. These two drug types alter GH release through distinct and complimentary mechanisms. Such combination therapy tends to produce substantial synergy with regard to GH release. When another short acting GHRP peptide is used with Mod GRF 1-29, the two are generally administered at the same time to maximize the resulting GH peak.

Mod GRF 1-29 is not available as a prescription drug product. It is sold exclusively as a ‘research compound’ or gray market supplement. Note that the quality of gray market products can be difficult to assure.

1 Human Growth Hormone-Releasing Factor (hGRF)1-29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog. Lucie Jette et al. Endocrinology 146: 3052–3058, 2005

2 Differential effects of N-terminal modifications on the biological potencies of growth hormone releasing factor analogues with varying chain lengths. Coy, D. H., W.A. Murphy, V. A. Lance and M. L. Heiman. J Med Chem 30:2122, 1987

3 Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions. Thevis M et al. Expert Rev Proteomics. 2014 Dec;11(6):663-73

4 Pharmacokinetic Evaluation of Superactive Analogues of Growth Hormone Releasing Factor (1-29)-Amide. B Rafferty et al. Peptides. Vol. 9. pp 207209.1988

5 Human Growth Hormone-Releasing Factor (hGRF)1-29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog. Lucie Jette? et al. Endocrinology (2005) 146 (7): 3052-3058.