What Is CJC-1295 No DAC? Modified GRF 1-29 Research Overview

Introduction to CJC-1295 No DAC

CJC-1295 no DAC, also known as Modified GRF (1-29), is a synthetic analog of the first 29 amino acids of growth hormone-releasing hormone (GHRH). The compound has been the subject of published in-vitro research examining hypothalamic-pituitary signaling pathways. Identified under CAS number 863288-34-0, this peptide represents a structurally modified version of the endogenous GHRH fragment, engineered for enhanced stability in laboratory assay conditions.

The "no DAC" designation distinguishes this compound from the DAC-conjugated variant (CJC-1295 with DAC), which incorporates a Drug Affinity Complex. This distinction is important for researchers, as the two compounds exhibit different pharmacokinetic profiles in published studies and serve different purposes in laboratory investigations. Origin Research Labs provides CJC-1295 no DAC at >99.634% purity, independently verified by Janoshik Analytical.

GHRH and the Endogenous Signaling Framework

Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that has been extensively characterized in published biochemical literature. The endogenous form consists of 44 amino acids, though research conducted in the 1980s established that the first 29 residues (GHRH 1-29) retain full receptor-binding activity in in-vitro receptor binding assays. This truncated form served as the structural starting point for the development of CJC-1295 no DAC.

The GHRH receptor (GHRH-R) is a G-protein-coupled receptor that has been studied extensively in cell-based assay systems. Published literature documents that GHRH-R activation in transfected cell lines triggers intracellular cyclic AMP (cAMP) accumulation, which can be quantified using standard reporter assays. This well-characterized signaling cascade makes GHRH-R an important target in receptor pharmacology research.

In-vitro studies using isolated pituitary cell preparations and GHRH-R-expressing cell lines have provided the foundation for understanding the structure-activity relationships of GHRH and its analogs. These controlled laboratory systems allow researchers to examine receptor binding, signal transduction, and downstream molecular events in a reproducible manner.

Structural Modifications: From GHRH (1-29) to Mod GRF

The native GHRH (1-29) sequence is susceptible to rapid enzymatic degradation in biological media, which presents challenges for laboratory experiments requiring sustained exposure periods. Researchers identified specific residue positions where amino acid substitutions could confer resistance to enzymatic cleavage without disrupting receptor-binding affinity, as measured by in-vitro competition binding assays.

CJC-1295 no DAC incorporates four amino acid substitutions relative to the native GHRH (1-29) sequence:

• Position 2: Alanine replaced with D-Alanine (D-Ala2) -- confers resistance to dipeptidyl peptidase-IV (DPP-IV) cleavage as demonstrated in enzyme inhibition assays
• Position 8: Asparagine replaced with Glutamine (Gln8) -- reduces asparagine deamidation observed during extended incubation in aqueous solutions
• Position 15: Glycine replaced with Alanine (Ala15) -- enhances alpha-helical stability as measured by circular dichroism spectroscopy
• Position 27: Methionine replaced with Leucine (Leu27) -- eliminates methionine oxidation artifacts in assay systems

Each substitution has been independently validated in published structure-activity relationship (SAR) studies. The combined modifications result in a peptide that retains high affinity for the GHRH receptor in binding assays while exhibiting substantially improved chemical stability under standard laboratory storage and assay conditions.

DAC vs. No-DAC: Chemistry Comparison

The distinction between CJC-1295 with DAC and CJC-1295 without DAC (Mod GRF 1-29) is a frequent point of inquiry among researchers. The two compounds share the same core 29 amino acid sequence with the four substitutions described above, but differ in a critical chemical modification.

CJC-1295 with DAC

The DAC (Drug Affinity Complex) version incorporates a reactive moiety -- specifically a maleimidopropionic acid linker -- that forms a covalent bond with albumin via a thiol exchange reaction. This bioconjugation has been characterized in published analytical chemistry studies using mass spectrometry and chromatographic techniques. The albumin conjugation significantly alters the compound's behavior in serum-containing media, which is relevant for researchers designing assays with albumin-containing culture conditions.

CJC-1295 without DAC (Mod GRF 1-29)

The no-DAC variant lacks this reactive linker and therefore does not undergo albumin conjugation. In comparative in-vitro studies, the two forms exhibit different stability profiles in serum-containing versus serum-free media. The no-DAC form is often preferred for acute-exposure experiments and receptor-binding studies where the pharmacokinetic influence of albumin binding is not desired as a variable.

Published literature comparing the two variants has documented distinct profiles in receptor activation kinetics assays. The no-DAC form achieves receptor occupancy more rapidly in cell-based systems, while the DAC form provides more sustained receptor stimulation in assays utilizing serum-supplemented media. Researchers select between the two based on their specific experimental objectives and assay design requirements.

Pituitary Signaling Pathway Research In Vitro

A primary research application of CJC-1295 no DAC involves the study of pituitary signaling pathways using in-vitro model systems. Primary pituitary cell cultures, immortalized pituitary cell lines (such as GH3 and GH4C1 cells), and GHRH-R-transfected cell lines have all been employed in published studies examining the downstream effects of GHRH receptor activation.

In these controlled laboratory systems, researchers have used CJC-1295 no DAC to study:

• cAMP accumulation kinetics following receptor engagement, measured by ELISA and luminescence-based assays
• Protein kinase A (PKA) activation and substrate phosphorylation patterns via Western blot analysis
• CREB (cAMP response element-binding protein) phosphorylation as a downstream transcriptional marker
• Gene expression changes in pituitary cell lines using RT-qPCR and microarray approaches
• Calcium mobilization patterns using fluorometric indicators in live-cell imaging platforms

These in-vitro studies have contributed to the broader understanding of GHRH receptor signal transduction and have been published in journals including Endocrinology, Molecular and Cellular Endocrinology, and Journal of Endocrinology.

Receptor Binding and Selectivity Research

Published radioligand displacement assays have characterized the binding affinity of CJC-1295 no DAC for the GHRH receptor. These studies, performed using membrane preparations from cells expressing recombinant GHRH-R, have established the compound's binding parameters (K_i values) relative to native GHRH and other structural analogs.

Selectivity profiling has been conducted in panels of cell lines expressing different G-protein-coupled receptors. Published data from these screens indicate that the compound's binding activity is specific to the GHRH receptor, with minimal cross-reactivity at other related receptor subtypes tested in vitro. This selectivity profile is an important consideration for researchers using the peptide as a pharmacological tool in signaling studies.

Stability and Handling in Research Settings

The four amino acid substitutions in CJC-1295 no DAC were specifically designed to address stability challenges encountered during laboratory use. Published stability studies have characterized the compound's degradation profile under various conditions, including different pH values, temperatures, and buffer compositions commonly used in research laboratories.

Key findings from published stability assessments include:

• The D-Ala2 substitution confers resistance to DPP-IV, a ubiquitous serum protease that cleaves the native peptide at position 2-3
• Lyophilized material maintains integrity for extended periods when stored at -20°C, as verified by HPLC analysis
• Reconstituted solutions exhibit optimal stability in slightly acidic buffers (pH 5-6) based on published degradation kinetics studies
• The Leu27 substitution eliminates methionine sulfoxide formation, a common oxidative modification that can alter binding affinity

Published Literature Overview

CJC-1295 and its structural variants have been documented in the peer-reviewed literature since the early 2000s. The published research spans several disciplines, including endocrine pharmacology, receptor biology, peptide chemistry, and analytical methodology. Researchers can access this body of literature through PubMed, Google Scholar, and institutional databases.

Areas of active research interest documented in recent publications include the development of improved in-vitro assay systems for GHRH receptor characterization, comparative structure-activity studies among GHRH analogs, and the application of advanced analytical techniques (LC-MS/MS, capillary electrophoresis) for peptide quantification and purity assessment in research materials.

Purity and Quality at Origin Research Labs

Origin Research Labs provides CJC-1295 no DAC at >99.634% purity, verified by independent third-party analysis from Janoshik Analytical. Each batch undergoes HPLC purity assessment, mass spectrometric identity confirmation, and residual solvent analysis. A Certificate of Analysis (COA) is provided with every order, enabling researchers to document the quality of materials used in their experimental work.

Summary

CJC-1295 no DAC (Modified GRF 1-29) is a well-characterized synthetic GHRH analog (CAS 863288-34-0) incorporating four targeted amino acid substitutions to enhance stability in laboratory settings. Its documented receptor binding properties, established role in pituitary signaling pathway research conducted in vitro, and clear differentiation from the DAC-conjugated variant make it a valuable tool for research professionals investigating GHRH receptor biology and related signaling mechanisms.