How does Cagriniltide work? What is its mechanism of action?

Mecanismo de Acao Cagriniltide functions como um(a) non-selective dual agonist of ambos(as) calcitonin receptors (CTR) and amylin receptors (AMY1R, AMY2R, AMY3R) — heterodimers of CTR with RAMPs 1, 2, or 3.[3][12] Receptor Targets & Binding TargetInteractionEvidence Calcitonin Receptor (CTR)Non-selective agonist; class B1 GPCR; EC50 62 pMKruse et al. (2021); Cao et al. (2025) cryo-EM[3][9] AMY1R (CTR+RAMP1)Potent agonist; "bypass" conformation bindingRAMP1/3 KO abolishes the anorectic response (

What are the research applications of Cagriniltide?

Aplicacoes de Pesquisa Published literature (clinical trials used the pharmaceutical formulation; see References) covers: Receptor Pharmacology — Cryo-EM structural biology of dual AMYR/CTR agonism; RAMP-dependent signaling; "bypass" vs "CT-like" receptor conformations; rapid-dissociation kinetics preventing dessensibilizacao.[9][10]

What does the research summary say about Cagriniltide?

Resumo da Pesquisa Pre-clinica Key Preclinical Studies EstudoModeloPrincipais AchadosRef Carvas et al. (2025)129S2/SvEv mice — WT vs RAMP1/3 KO; 3–300 nmol/kg30 nmol/kg: 24h food intake ↓51%; 57% fewer AP neurons ativou in KO[8] Kruse et al. (2021)Male SD rats — 0.1–30 nmol/kg; PK: 10 nmol/kgFood intake reduziu for varios(as) days at 1–10 nmol/kg; T½ 20–27h[3] Dahl et al. (2024)Rats — 30 nmol/kg single administrationFood intake reduziu 85% at 0–24h and 84% at 24–48h; EC50: hAMY3R 49 pM, hCTR 62

How should Cagriniltide be stored?

Liofilizado: -80°C (2 anos) ou -20°C (1 ano), vedado e protegido da luz e da umidade.

Cagriniltide: Mechanism of Action

Q: What is Cagriniltide?

Visao Geral da Pesquisa Cagriniltide (AM833/NN1213) is a long-acting acylated analogue of human amylin — a 37-aminoacido pancreatic hormone co-secreted with insulin que regula satiety and glucose homeostasis. Native human amylin is unstable, prone to amyloid fibril formation, and has a muito short meia-vida. The first-generation analogue, pramlintide, requer multiplas administracoes diarias.[2] Cagriniltide overcomes these limitations through C20 fatty diacid acylation (via γ-glutamic acid space

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19 Citacoes PubMedRevisado por EspecialistasUltima Revisao: fevereiro de 2026

Mecanismo de Acao

Cagriniltide functions como um(a) non-selective dual agonist of ambos(as) calcitonin receptors (CTR) and amylin receptors (AMY1R, AMY2R, AMY3R) — heterodimers of CTR with RAMPs 1, 2, or 3.[3][12]

Receptor Targets & Binding

Target	Interaction	Evidence
Calcitonin Receptor (CTR)	Non-selective agonist; class B1 GPCR; EC50 62 pM	Kruse et al. (2021); Cao et al. (2025) cryo-EM[3][9]
AMY1R (CTR+RAMP1)	Potent agonist; "bypass" conformation binding	RAMP1/3 KO abolishes the anorectic response (mice)[8]
AMY3R (CTR+RAMP3)	Potent agonist; EC50 49 pM (hAMY3R)	Carvas et al. (2025): required for the response in mice[8][13]
CGRPR / AM1R / AM2R	No or muito baixo(a) activity — selective for amylin/calcitonin axis	Fletcher et al. (2021)[12]

Sinalizacao a Jusante

Pathway	Effect	Consequence
Gs / Adenylyl Cyclase / cAMP	Gs-protein ativacao → adenylyl cyclase → intracellular cAMP accumulation	Primary cascata de sinalizacao for satiety[9]
Neuronal cFos (AP/NTS/LPBN)	Induces cFos expression in area postrema, nucleus of solitary tract, lateral parabrachial nucleus	Satiety signaling; 57% fewer AP neurons in RAMP1/3 KO[8]
Gastric Emptying	Delays gastric emptying	Gastric-emptying endpoints
Glucagon Suppression	Suppresses postprandial glucagon from pancreatic α-cells	Pancreatic signaling endpoints[6]

Unique Binding Characteristics

Property	Cagriniltide	Salmon Calcitonin
Receptor Conformation	"Bypass" (stabilized by ionic lock N14E–V17R)	"CT-like" conformation
Residence Time	3–6 minutes (rapid dissociation)	45–60 minutes (slow dissociation)
Desensibilizacao	Less receptor downregulacao reported	Receptor downregulacao reported

RAMP Dependence: Carvas et al. (2025) demonstrated que the food-intake responses to cagriniltide in mice are strictly dependent on AMY1R and AMY3R — knockout of RAMP1 and RAMP3 abolished the response, with 57% fewer neurons ativou no(a) area postrema.[8]

Editorial Research Note

“Resumo da Pesquisa Pre-clinica Key Preclinical Studies EstudoModeloPrincipais AchadosRef Carvas et al.”

Pure U.S. Peptides Research Standards TeamInternal editorial group summarising published peptide research for an audience of qualified independent investigators.

Referencias

Perguntas de Pesquisa Relacionadas

→ What Is Cagriniltide?→ Cagriniltide: Research Applications → Cagriniltide: Safety Profile & Research Summary → Cagriniltide: Chemical Properties → Storing Cagriniltide: Best Practices

Related research

GLP2-T — Mechanism of action GLP3-R — Mechanism of action

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