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What Is CJC-1295?

CJC-1295 refers to a family of synthetic analogues of human growth hormone-releasing hormone (GHRH) residues 1–29, developed by Conjuchem Biotechnologies (Montréal, Canada). Two primary research variants are used: CJC-1295 No DAC (also called Modified GRF 1-29 or Mod GRF 1-29), and CJC-1295 with DAC (Drug Affinity Complex), which incorporates a reactive maleimidopropionic acid–lysine conjugate enabling covalent binding to serum albumin. Both variants share a modified GHRH(1-29) backbone incorporating four amino acid substitutions designed to prevent DPP-IV cleavage, asparagine deamidation, and methionine oxidation, while preserving full GHRH receptor (GHRHR) agonist activity. The DAC technology extends circulating half-life from approximately 30 minutes (No DAC) to approximately 6–8 days (with DAC).

Chemical Properties

Property	CJC-1295 No DAC (Mod GRF 1-29)	CJC-1295 with DAC
CAS Number	2097819-38-0	863288-34-0
Molecular Weight	~3367.9 g/mol	~3647.3 g/mol
Amino Acid Count	29 residues	29 residues + MPA-Lys conjugate
DAC linker	None	Maleimidopropionic acid (MPA) on Lys
Albumin binding	None	Covalent (Cys34 of serum albumin)
Half-life (research models)	~20–30 min	~6–8 days
Receptor target	GHRHR (Gs-coupled GPCR)	GHRHR (Gs-coupled GPCR)
Also known as	Modified GRF(1-29); Mod GRF 1-29; Sermorelin analogue	CJC-1295; long-acting GHRH analogue

Historical Development and Discovery

CJC-1295 was developed by Conjuchem Biotechnologies as part of their Biocon drug conjugation platform, which explored reactive electrophilic linkers for forming covalent bonds between peptide drugs and endogenous plasma proteins. The target for CJC-1295 was Cys34 of human serum albumin (HSA), the only free thiol in albumin, offering a selective site for Michael addition chemistry via a maleimide-functionalized peptide. By incorporating a maleimidopropionic acid (MPA) group on a C-terminal lysine residue of a modified GHRH(1-29) backbone, Conjuchem created a peptide that rapidly and selectively alkylates HSA Cys34 after subcutaneous administration, producing an albumin–peptide conjugate with HSA’s long circulating half-life (~19 days) while retaining GHRHR agonist activity.

The Modified GRF(1-29) backbone common to both CJC-1295 variants incorporates four amino acid substitutions relative to native GHRH(1-29). These substitutions were selected to address three primary stability liabilities: (1) N-terminal DPP-IV cleavage of the Tyr¹-Ala² bond; (2) asparagine deamidation at Asn⁸; and (3) methionine oxidation at Met²⁷. The resulting modified backbone shows substantially enhanced metabolic stability relative to GHRH(1-29) and the pharmaceutical GHRH analogue sermorelin, while maintaining subnanomolar affinity at GHRHR. Research into the CJC-1295 series expanded through the 2000s with studies examining GH and IGF-1 pharmacodynamics, body composition, and bone biology in animal models and humans.

Chemical Architecture and Structural Features

Structural Feature	Detail
Parent peptide	GHRH(1-29)-NH₂ (first 29 amino acids of human GHRH, C-terminal amide)
Modification 1	DPP-IV resistance: N-terminal substitution blocking Tyr¹-Ala² cleavage site
Modification 2	Asn⁸→Ala: eliminates asparagine deamidation (chemical stability)
Modification 3	Gln¹⁵ stabilization: protects against hydrolytic instability at this position
Modification 4	Met²⁷→Leu (or Ala): eliminates methionine oxidation (storage and plasma stability)
C-terminus	Amidated (-NH₂) in both variants
DAC linker (with DAC only)	Lys at C-terminal extended region carries maleimidopropionic acid (MPA); reacts with HSA Cys34 via Michael addition
Albumin conjugate (with DAC)	CJC-1295–HSA: covalent amide bond; retains GHRHR agonist activity

Research Mechanisms

Published research has characterized the following molecular and physiological mechanisms relevant to the CJC-1295 peptide family:

• GHRHR agonism: Both CJC-1295 variants act as agonists of the GHRH receptor (GHRHR), a Gs-coupled GPCR expressed on pituitary somatotroph cells. Receptor activation stimulates adenylyl cyclase, raises intracellular cAMP, activates PKA, and promotes pulsatile GH secretion in a pattern consistent with physiological GHRH signalling.
• Albumin-mediated half-life extension (with DAC): The MPA-Lys DAC conjugate reacts with Cys34 of serum albumin in vivo via Michael addition chemistry, forming a stable covalent thioether bond. The resulting albumin–CJC-1295 conjugate inherits albumin’s extended half-life (~19 days in humans), resulting in a prolonged, low-amplitude GH secretion pattern distinct from the sharp GH pulses produced by the No DAC variant.
• DPP-IV resistance: The N-terminal substitution at position 2 in the Modified GRF(1-29) backbone sterically prevents DPP-IV from cleaving the N-terminal dipeptide, the primary inactivation mechanism for native GHRH(1-29). This modification is shared by both CJC-1295 variants.
• GH–IGF-1 axis modulation: GH released in response to CJC-1295 GHRHR stimulation drives hepatic IGF-1 synthesis. Research studies have quantified dose-dependent IGF-1 elevation as a pharmacodynamic endpoint and have characterized the distinct temporal profiles of IGF-1 response for the No DAC (pulsatile) versus DAC (sustained) variants.
• Synergy with GHSR-1a agonists: As a GHRHR agonist, CJC-1295 operates on the Gs/cAMP pathway, which is complementary to the Gq/11/calcium pathway activated by GHSR-1a agonists (such as ipamorelin). Research characterizes supraadditive GH pulse amplification when both receptor classes are simultaneously activated.

Research Areas

GH Pulse Pharmacodynamics Research

A key area of CJC-1295 research has been characterizing the distinct GH and IGF-1 pharmacodynamic profiles generated by the No DAC versus DAC variants. Phase 1 and Phase 2 clinical pharmacology studies by Ionescu and Frohman demonstrated that a single administration of CJC-1295 with DAC produced sustained IGF-1 elevation lasting 14 days or more, with mean IGF-1 increases of 1.5- to 3-fold above baseline, reflecting the albumin-mediated prolongation of peptide exposure. The No DAC variant, by contrast, produces short, sharp GH pulses resembling physiological GHRH-stimulated release, with IGF-1 returning to baseline within 24 hours. These contrasting profiles have made the CJC-1295 family a reference system for studying pulse versus continuous GH secretion pattern effects.

Body Composition and Metabolic Research

GH secretion stimulated by GHRHR agonism drives lipolysis in visceral and subcutaneous adipose depots and promotes lean tissue anabolism via IGF-1. Research using CJC-1295 has examined GH-mediated body composition changes including effects on fat mass, lean mass, and body weight in both rodent and human study populations. These studies position CJC-1295 as a pharmacological tool for investigating GH axis contributions to metabolic regulation and adipose biology.

Albumin-Conjugation Drug Delivery Research

The DAC technology platform underlying CJC-1295 with DAC has broader implications for peptide pharmacology research beyond GHRH signalling. The selective, covalent conjugation to albumin Cys34 via maleimide chemistry represents a general strategy for extending the half-life of short-acting bioactive peptides without compromising receptor binding activity. Research into this conjugation approach has examined reaction kinetics, conjugate stability, receptor affinity retention, and pharmacokinetic profiles, contributing to the broader field of albumin-binding prodrug and drug conjugation strategies.

Bone Biology Research

GH and IGF-1 are established regulators of bone mineral density and skeletal architecture. Preclinical research using CJC-1295 and related GHRH analogues has examined GH-axis stimulation effects on bone mineral density, cortical bone geometry, and trabecular microarchitecture in aged or GH-deficient animal models, contributing to understanding of how GH pulse amplitude and duration influence skeletal outcomes.

Frequently Asked Questions

What is the difference between CJC-1295 with DAC and CJC-1295 No DAC?

Both variants share the same Modified GRF(1-29) backbone — a GHRH(1-29) analogue with four stabilizing amino acid substitutions. CJC-1295 No DAC (Modified GRF 1-29) does not carry an albumin-binding linker and has a short circulating half-life (~20–30 min), producing acute GH pulses. CJC-1295 with DAC carries a maleimidopropionic acid–lysine conjugate that covalently binds to Cys34 of serum albumin after administration, extending functional half-life to approximately 6–8 days and producing sustained IGF-1 elevation. The DAC suffix specifies which variant is referenced.

What is the CAS number for CJC-1295?

CJC-1295 with DAC has CAS registry number 863288-34-0 and a molecular weight of approximately 3647.3 g/mol. CJC-1295 No DAC (Modified GRF 1-29) has CAS 2097819-38-0 and a molecular weight of approximately 3367.9 g/mol. The two variants have distinct CAS numbers because the DAC maleimide-lysine conjugate constitutes a chemically distinct molecular entity.

What receptor does CJC-1295 act on?

CJC-1295 (both variants) is an agonist of the growth hormone-releasing hormone receptor (GHRHR), a Gs protein-coupled receptor expressed on anterior pituitary somatotroph cells. GHRHR activation stimulates adenylyl cyclase, raises intracellular cAMP, and triggers pulsatile GH secretion. This is the same receptor targeted by tesamorelin and native GHRH, but distinct from the GHSR-1a (ghrelin receptor) targeted by ipamorelin and GHRP-class peptides.

What does “Modified GRF 1-29” mean?

“Modified GRF(1-29)” designates the Modified Growth Releasing Factor comprising residues 1 through 29 of GHRH — the minimum active fragment of GHRH retaining full GHRHR binding activity — with four amino acid substitutions for stability. “Modified” specifies these substitutions versus the parent GHRH(1-29) sequence (sermorelin). This is the backbone used in both CJC-1295 variants and distinguishes Mod GRF 1-29 from sermorelin, which is the unmodified GHRH(1-29) amide.

What is the DAC technology in CJC-1295?

DAC (Drug Affinity Complex) is Conjuchem’s proprietary albumin-binding technology. A maleimidopropionic acid (MPA) group is covalently attached to a lysine residue on the C-terminal region of the peptide. After administration, the maleimide undergoes a Michael addition reaction with the free thiol of Cys34 on serum albumin — the only free cysteine in human serum albumin — forming a stable thioether bond. The resulting albumin–peptide conjugate inherits albumin’s long circulating half-life while the GHRH peptide moiety remains accessible to GHRHR on pituitary somatotrophs.

Is CJC-1295 the same as sermorelin?

No. Sermorelin is the unmodified GHRH(1-29) amide sequence with no amino acid substitutions. CJC-1295 No DAC (Modified GRF 1-29) is GHRH(1-29) with four stabilizing substitutions that improve metabolic stability relative to sermorelin. CJC-1295 with DAC additionally incorporates the albumin-binding DAC conjugate for extended half-life. All three peptides are GHRHR agonists acting on the same receptor, but with distinct half-lives and stability profiles.

How does CJC-1295 interact with ipamorelin?

CJC-1295 (GHRHR agonist) and ipamorelin (GHSR-1a agonist) stimulate GH secretion through distinct, complementary intracellular signalling pathways — Gs/cAMP and Gq/11/calcium, respectively. Research characterizes the combination as producing supraadditive GH pulse amplification relative to either compound alone, reflecting convergent second messenger signalling on anterior pituitary somatotrophs. This receptor-level synergy has made the CJC-1295 + ipamorelin combination a commonly studied pairing in GH axis pharmacology research.

What is the molecular weight of CJC-1295?

CJC-1295 No DAC (Modified GRF 1-29) has a molecular weight of approximately 3367.9 g/mol. CJC-1295 with DAC has a molecular weight of approximately 3647.3 g/mol, reflecting the additional mass of the maleimidopropionic acid–lysine DAC linker appended to the peptide backbone.

Published Research

The following peer-reviewed studies are representative of the published research literature on CJC-1295 and related Modified GRF(1-29) analogues:

• Ionescu M, Frohman LA. (2006). Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. Journal of Clinical Endocrinology & Metabolism. PMID: 16352683
• Jetté L, et al. (2005). hGRF analogs with improved biological activity through albumin binding. Journal of Endocrinology. PMID: 15845924
• Thorner MO, et al. (1997). Growth hormone-releasing hormone analog: sermorelin. Journal of Clinical Endocrinology & Metabolism. PMID: 9048521
• Bowers CY, et al. (1990). Synergistic release of growth hormone by GHRH and GHRP. Endocrinology. PMID: 2190740
• Walker RF. (2006). Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? Clinical Interventions in Aging. PMID: 18046878
• Alba M, et al. (2006). Once-monthly administration of CJC-1295, a long-acting growth hormone-releasing hormone analog, normalizes growth failure in the growth hormone-deficient Lewis dwarf rat. Endocrinology. PMID: 16439462

Research Use Only Disclaimer

CJC-1295 (both with DAC and No DAC variants) as supplied by ITide Laboratories is intended for laboratory research purposes by qualified professionals only. Not for human, animal, diagnostic, or therapeutic use. This compound has not been evaluated by the FDA for clinical application, is not manufactured to pharmaceutical standards, and all applicable local, state, and federal regulations governing research compounds apply.