GLP-1 C — Published Research

C is a dual amylin and calcitonin receptor agonist (DACRA) that binds to amylin receptor subtypes AMY1R, AMY2R, and AMY3R, as well as the calcitonin receptor (CTR). Amylin receptors are heterodimeric complexes formed by the calcitonin receptor (CTR) co-expressed with receptor activity-modifying proteins (RAMPs 1-3). C demonstrates nanomolar potency at these receptor complexes in cAMP accumulation assays. The compound’s broad amylin receptor engagement profile — activating all three AMY subtypes — provides a distinct signaling signature compared to native amylin, which shows preferential AMY1R and AMY3R activity. For laboratory research use only.

Citation: Cao C, Yang K, Liu S, et al. “Structural basis for the recognition of C by amylin receptors.” Nat Commun. 2025;16:1234. PubMed

Despite sometimes being categorized alongside GLP-1 compounds, C is pharmacologically distinct. It has no meaningful affinity for the GLP-1 receptor, GIP receptor, or glucagon receptor. C acts exclusively through amylin and calcitonin receptor signaling pathways, which are expressed in different tissue distributions than GLP-1R. While GLP-1 receptor agonists primarily signal through pancreatic and CNS GLP-1R populations, amylin receptors are concentrated in the area postrema and other hindbrain regions. The distinct receptor targets mean C engages non-overlapping signaling cascades compared to the GLP-1 agonist class. For laboratory research use only.

Citation: Cao C, Yang K, Liu S, et al. “Structural basis for the recognition of C by amylin receptors.” Nat Commun. 2025;16:1234. PubMed

Native human amylin (37 amino acids) has a circulating half-life of approximately 13 minutes due to rapid renal clearance and enzymatic degradation. C overcomes this through N-terminal lipidation with a C-18 fatty diacid moiety, enabling high-affinity non-covalent binding to serum albumin. This albumin association creates a circulating reservoir, extending the pharmacokinetic half-life to approximately 7 days. Additional modifications include amino acid substitutions that confer resistance to amidase and protease degradation while preserving receptor binding geometry. Cryo-EM structural studies have elucidated how C maintains receptor engagement despite these modifications. For laboratory research use only.

Citation: Cao C, Yang K, Liu S, et al. “Structural basis for the recognition of C by amylin receptors.” Nat Commun. 2025;16:1234. PubMed

Because C engages amylin/calcitonin receptors — pharmacologically independent from GLP-1 signaling — it has been investigated in combination with GLP-1 receptor agonists in research settings. The non-overlapping receptor targets (AMY1-3R/CTR vs. GLP-1R) engage distinct downstream signaling pathways, providing a rationale for combination investigation. The co-formulation GLP-1 C + GLP-1 S pairs C with GLP-1 S in a single formulation, combining amylin receptor agonism with GLP-1 receptor agonism. Preclinical receptor binding studies confirm no competitive interaction between the two compounds at their respective receptor targets. For laboratory research use only.

Citation: Cao C, Yang K, Liu S, et al. “Structural basis for the recognition of C by amylin receptors.” Nat Commun. 2025;16:1234. PubMed