Source comparison
Receptor Pharmacology: GHRHR vs GHS-R1a and CD36
CJC-1295 is a synthetic GHRH analogue (29-amino acid peptide, MW ~3367 Da non-DAC, ~3647 Da DAC) that acts exclusively at the GHRH receptor (GHRHR). GHRHR is a class B GPCR coupled to Gαs-adenylyl cyclase-cAMP-PKA-CREB, and is expressed predominantly in pituit
This comparison does not assign a generated winner or score.
- CJC-1295 is a synthetic GHRH analogue (29-amino acid peptide, MW ~3367 Da non-DAC, ~3647 Da DAC) that acts exclusively at the GHRH receptor (GHRHR). GHRHR is a class B GPCR coupled to Gαs-adenylyl cyclase-cAMP-PKA-CREB, and is expressed predominantly in pituitary somatotrophs. CJC-1295’s selectivity for GHRHR is essentially absolute — it produces no GHS-R1a activity, no CD36 binding, and no activity at any receptor outside the GHRHR-expressing pituitary compartment. The EC₅₀ at GHRHR is approximately 0.5 nM for non-DAC forms; the DAC modification (via maleimidoproprionic acid linkage to serum albumin Cys-34) extends half-life from 6–8 hours (non-DAC) to 6–8 days, without altering GHRHR affinity.
- Hexarelin (His-D-2-MeTrp-Ala-Trp-D-Phe-Lys-NH₂, MW ~887 Da) occupies a unique position in the GH secretagogue landscape by operating through two distinct receptors. At GHS-R1a, Hexarelin’s Ki is approximately 0.1–0.3 nM — substantially higher affinity than Ipamorelin (~1.0–1.5 nM) or GHRP-6 (~3.4 nM). This high GHS-R1a affinity drives maximal GH secretion but also produces robust ACTH and cortisol secretion (2.8–3.4× above baseline) and significant prolactin release — off-target effects entirely absent in CJC-1295.
- More fundamentally, Hexarelin — unlike all other GHS-R1a agonists — also binds the CD36 scavenger receptor (Kd ~1.8 nM in cardiac membrane preparations). CD36 is expressed on cardiomyocytes, macrophages, smooth muscle cells and adipocytes, and mediates effects including fatty acid transport, oxidised LDL uptake, and — crucially for research — cardioprotective signalling via PI3K-Akt-eNOS in ischaemia-reperfusion (I/R) models. This CD36 activity is GHS-R1a-independent (confirmed in GHS-R1a knockout mice, where Hexarelin retains 38–44% of its cardiac protection) and distinguishes Hexarelin from every other GH secretagogue.