CJC-1295 (No DAC) + Ipamorelin Blend 10mg (5mg/5mg)

This pre-mixed lyophilized blend combines CJC-1295 without DAC (Modified GRF 1-29, MW 3,367.97 Da) at 5mg and Ipamorelin (MW 711.85 Da) at 5mg in a single vial, providing two structurally distinct peptides that target independent G-protein-coupled receptor (GPCR) signaling cascades. Both components are co-lyophilized and freely soluble in aqueous buffers upon reconstitution.

CJC-1295 without DAC (Mod GRF 1-29) component: A tetrasubstituted 29-amino acid analog of human growth hormone-releasing hormone (GHRH) fragment 1-29. Four targeted substitutions enhance stability while preserving full GHRH receptor activity: Position 2: D-Ala (prevents DPP-4 N-terminal cleavage); Position 8: Gln (reduces asparagine rearrangement and amide hydrolysis); Position 15: Ala (enhances receptor bioactivity); Position 27: Leu (prevents methionine oxidation). CJC-1295 binds the GHRH receptor (GHRHR), a G_s-protein-coupled receptor on pituitary somatotroph cells, activating adenylate cyclase and increasing intracellular cAMP, which activates PKA and subsequently CREB for target gene transcription.

Ipamorelin component: A synthetic pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) with a molecular weight of 711.85 Da, first characterized by Raun et al. (1998). It selectively binds and activates the growth hormone secretagogue receptor type 1a (GHS-R1a, also known as the ghrelin receptor), a G_q-protein-coupled receptor. Activation triggers the IP₃/DAG signaling cascade: phospholipase C (PLC) hydrolyzes PIP₂ into inositol trisphosphate (IP₃) and diacylglycerol (DAG), leading to protein kinase C (PKC) activation and calcium mobilization from intracellular stores. Ipamorelin is distinguished from earlier ghrelin mimetics (GHRP-6, GHRP-2) by its high receptor selectivity.

The two receptor pathways are biochemically independent and converge at the somatotroph cell level: the GHRHR/cAMP/PKA pathway primarily drives gene transcription and vesicle priming, while the GHS-R1a/PLC/Ca²⁺/PKC pathway drives calcium-dependent exocytosis. Simultaneous activation of both cascades has been reported to produce supra-additive signaling responses in pituitary cell culture models.

Supplied as a lyophilized powder for in vitro research applications only. Not for human or veterinary use.

In Vitro Research Applications: This blend is designed for dual-pathway GPCR signaling research using pituitary-derived cell lines and primary somatotroph cultures. Applicable assay formats include cAMP accumulation assays for GHRHR-mediated G_s signaling (HTRF, LANCE, or FRET-based detection), intracellular calcium flux assays for GHS-R1a-mediated G_q signaling (Fura-2 AM or Fluo-4 calcium indicators), and combined endpoint measurement to characterize pathway convergence. Cell models include GH3 and GH4C1 rat pituitary tumor cell lines, as well as primary dispersed anterior pituitary cultures.

Signaling Pathway Studies: The blend enables comparative analysis of two independent GPCR signaling cascades converging on the same cellular endpoint. Research applications include quantification of PKA substrate phosphorylation (phospho-CREB) via Western blot for the CJC-1295/GHRHR arm, PKC activation and calcium store release kinetics for the Ipamorelin/GHS-R1a arm, and combined pathway output measurements. The GHS-R1a selectivity of Ipamorelin (no significant cross-activation of ACTH, cortisol, or prolactin pathways) makes it a preferred reference compound for clean receptor pharmacology studies versus earlier-generation ghrelin mimetics.

Molecular Characterization: Both components can be identified simultaneously by ESI-MS with distinct mass peaks at 3,367.97 Da and 711.85 Da. Purity of the blend is assessed by reversed-phase HPLC with dual-peak resolution. CJC-1295 DPP-4 resistance can be evaluated by incubation with recombinant enzyme and time-course HPLC monitoring. Ipamorelin receptor selectivity is confirmable by parallel cAMP and calcium flux assays across GHS-R1a, GHRHR, and control receptor-expressing cell lines.

References

1. Raun K, et al. (1998) Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol, 139(5):552-561. PMID: 9849822
2. Teichman SL, et al. (2006) Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab, 91(3):799-805. PMID: 16352683
3. Jimenez-Reina L, et al. (2002) Ipamorelin, a new growth-hormone-releasing peptide, induces GH secretion in vitro from cultured rat pituitary cells. J Endocrinol Invest, 25(6):542-548.