CAGRI Long-Acting Dual Amylin & Calcitonin Receptor Agonist (DACRA)

TECHNICAL SPECIFICATIONS

• Product Reference : CAGRI — Long-Acting DACRA Research Compound
• Chemical Class : Lipidated synthetic amylin analogue (DACRA)
• Physical Format : Lyophilised powder — hermetically sealed research container
• Analytical Purity (recommended) : ≥98% by RP-HPLC
• Identity Confirmation : LC-MS — molecular weight and sequence confirmation per batch COA
• Solubilization System : Aqueous buffer pH 4.5–6.0 for laboratory stability studies
• Storage — Lyophilised : −20°C or below, desiccated, light-protected, hermetically sealed
• Storage — In Solution : −80°C; single-use research aliquots; avoid repeated freeze-thaw
• Regulatory Class : Research Use Only (RUO) — Not for administration to living organisms
• Endotoxin Screening : <1.0 EU/mg (LAL assay) — required for laboratory assay quality
• COA Requirement : Batch-specific: HPLC purity + LC-MS identity + lot number + stability data

Disclaimer : For Research Use Only (RUO). Not for human use.

Structural & Chemistry Details

Parameter	Detail
IUPAC / Chemical Class	Synthetic acylated 37-amino-acid amylin analogue with C20 fatty diacid N-terminal modification
CAS Registry	1393461-38-5
PubChem CID	167312356
Development Code	AM-833
Molecular Formula	C194H312N54O59S2 (approximate; 39-residue sequence with lipid chain)
Molecular Weight	~4,409 g/mol
Disulfide Bridge	Between residues 3 and 8 (conserved amylin scaffold)
Lipidation	N-terminal C20 fatty diacid chain — albumin binding; extended circulating half-life
Half-Life (PK research)	~159–195 hours (~7 days) — Phase 1 pharmacokinetic study (J Med Chem 2021)
Fibril Resistance Mechanism	14E/17R salt-bridge substitutions + 25P/28P/29P proline substitutions
Receptor Profile (cryo-EM)	Non-selective agonist: AMY1R, AMY2R, AMY3R, CTR (DACRA)
Primary CNS Signalling Locus	Area postrema (AP) and nucleus tractus solitarius (NTS) — confirmed by RAMP1/3 KO studies
Key Structural Reference	Bhatt et al., Nature Communications, vol. 16, article 3389 (2025) — cryo-EM; CC BY 4.0

Product Overview

Discovery and Scientific Background :

Amylin is a 37-amino acid peptide hormone co-secreted alongside insulin from pancreatic beta cells in direct response to nutrient intake. Its functions in satiety signalling, gastric motility modulation, and postprandial glucose handling have been studied since the 1980s (Cooper et al., 1987). [R2] Despite this pharmacological interest, clinical translation of native amylin was severely limited by its inherent chemical instability — specifically its propensity to form amyloid fibrils and its half-life of only seconds to minutes under physiological conditions. [R2, R3]

Pramlintide incorporates rat amylin sequence substitutions that reduce fibrillation. Its shorter reported half-life provides a structural and stability research comparison for longer-acting amylin analogues. [R3] Amylin and GLP-1 receptor signalling can be examined through distinct neuronal pathways in mechanistic research. [R11]

Cagrilintide (AM-833) emerged from a Novo Nordisk medicinal chemistry programme as a structurally optimised, lipidated, long-acting DACRA. The design strategy, SAR data, and Phase 1 pharmacokinetic results were published in the Journal of Medicinal Chemistry in 2021 (Enni et al.), establishing the scientific foundation for Phase 2 and Phase 3 research programmes. [R4]

Molecular Architecture

Cagrilintide (AM-833) emerged from a Novo Nordisk medicinal chemistry programme as a structurally optimised, lipidated, long-acting DACRA. The design strategy, SAR data, and Phase 1 pharmacokinetic results were published in the Journal of Medicinal Chemistry in 2021 (Enni et al.), establishing the scientific foundation for Phase 2 and Phase 3 research programmes. [R4]Five targeted structural modifications are incorporated:

• 14E and 17R substitutions — Stabilise the central alpha-helix through a salt bridge interaction.
• 25P, 28P, 29P proline substitutions — Reduce beta-sheet propensity and amyloid fibril formation — the primary instability mechanism of native amylin.
• C-terminal proline — Enhances potency specifically at the calcitonin receptor (CTR), supporting the DACRA pharmacological profile.
• N-terminal C20 fatty diacid lipidation — Albumin binding; half-life extension (~7 days). Does not reduce AMY3R binding potency vs native amylin. [R4]
• Retained AMY3R affinity — Specifically preserved in the SAR design programme alongside all other modifications. [R4]

Research Mechanism -2026 Laboratory Applications

All applications below concern laboratory research assays. For laboratory research use only. Not for use in humans or animals.

1-Amylin Receptor Pharmacology Research (AMY1R, AMY2R, AMY3R)

Amylin receptor subtypes are structurally defined by heterodimerisation of the calcitonin receptor (CTR) with one of three receptor activity-modifying proteins: RAMP1 (AMY1R), RAMP2 (AMY2R), or RAMP3 (AMY3R). [R6] RAMP1/3 double-knockout studies (Folgueira et al., eBioMedicine 2025) confirmed that Cagrilintide’s energy-balance signalling effects are specifically dependent on intact AMY1R and AMY3R function. [R8]

Science Advances research (Weston et al., 2025) further showed that each AMYR subtype exhibits distinct basal subunit equilibria — the ratio of assembled heterodimers to free CTR and RAMP subunits differs between subtypes and determines downstream cAMP signalling amplitude. AMY3R demonstrates the most stable heterodimer assembly due to a stronger RAMP3 transmembrane interaction. [R7]

Research endpoints: AMY1R/AMY2R/AMY3R/CTR binding affinity assays via cAMP reporter systems; RAMP-dependent receptor subtype assembly characterisation; Gs-coupled signalling kinetics via HTRF cAMP quantification; competitive displacement binding studies.

2-Cryo-EM Structural Biology and Receptor-Peptide Interaction Studies

Bhatt et al. (Nature Communications, vol. 16, article 3389, April 2025; DOI:10.1038/s41467-025-58680-y; Open Access CC BY 4.0) resolved cryo-EM structures of Cagrilintide bound to Gs-coupled active AMY1R, AMY2R, AMY3R, and CTR simultaneously — the first full receptor-complement structural dataset for any DACRA compound. The structures confirmed Cagrilintide’s non-selective receptor engagement and identified RAMP-specific extracellular domain positioning in receptor subtype discrimination. [R5]

Research endpoints: cryo-EM sample preparation for CTR/RAMP heterodimer complexes; comparative structural alignment of DACRA vs selective AMYR agonists; structure–activity relationship studies; lipidation effect on receptor engagement biophysics.

3- Hindbrain Neuronal Circuit Research – Area Postrema and NTS

The area postrema (AP) and adjacent nucleus tractus solitarius (NTS) are the neuroanatomical sites with the highest co-localised CTR and RAMP expression density in the CNS. [R6] RAMP1/3 KO research (Folgueira et al. 2025) confirmed these as the primary anatomical loci for Cagrilintide’s central signalling. In published wild-type mouse models, Cagrilintide produced statistically significant cFos-positive neuron increases in AP and NTS (P < 0.005). In RAMP1/3 KO models, both neuronal activation and energy-balance signals were substantially attenuated — confirming receptor-specific, region-specific mechanistic dependence. [R8]

Research endpoints: cFos immunostaining in AP and NTS in published CAGRI research studies; neuronal population mapping for AMY1R/AMY3R co-expression; hindbrain circuit connectivity tracing.

4 – Concentration-Response Characterisation and DACRA Pharmacology

Research endpoints receptor subtype potency profiling across AMY1R/AMY2R/AMY3R/CTR concentration gradients; combination index analyses for DACRA + GLP-1 receptor agonist models; albumin-binding characterisation and displacement kinetics for lipidated DACRA analogues.

5 – Peptide Synthesis and Analytical Chemistry Research

Cagrilintide’s 39-residue sequence, disulfide bridge (residues 3–8), N-terminal C20 fatty diacid, and multi-position substitutions make it a structurally demanding synthesis target. Modern SPPS (Merrifield 1963; Simon et al. 2014; Mijalis et al. 2017; Hartrampf et al. 2020) provides the methodological infrastructure for research-grade synthesis and analytical characterisation. [R14–R17]

Research endpoints: RP-HPLC purity profiling; LC-MS identity confirmation per batch COA; ThT aggregation assay (fibril formation: CAGRI vs native amylin); pH-dependent stability studies in aqueous research buffers (pH 4–7).

Receptor Pharmacology Summary

Sources: Bhatt et al. Nature Commun 2025; Folgueira et al. eBioMedicine 2025; Weston et al. Science Advances 2025

Receptor	Composition	Brain Region	Role in CAGRI Signalling
AMY1R	CTR + RAMP1	Area Postrema, NTS	Required — RAMP1 KO substantially impairs concentration-dependent energy-balance effects in published mouse models
AMY2R	CTR + RAMP2	Limited CNS expression	Structurally engaged (cryo-EM confirmed); metabolic dependency less characterised
AMY3R	CTR + RAMP3	Area Postrema, NTS	Required — RAMP3 KO substantially impairs energy-balance signalling; most stable heterodimer subtype
CTR (free)	CTR only	Multiple peripheral tissues	Co-engaged by CAGRI — basis of DACRA vs AMYR-selective classification

MOLECULAR STRUCTURE

Chemical structure of CAGRI

The 2025 cryo-EM structural data (Bhatt et al., Nature Communications) confirmed that the C20 lipid chain creates no steric interference with receptor binding domain engagement.

CAGRI (CID 167312356) full molecular structure — C194H312N54O59S2 — 39-residue lipidated amylin analogue showing N-terminal C20 fatty diacid chain, disulfide bridge (Cys3–Cys8), and proline substitutions at positions 25, 28, 29. Source: PubChem CID 167312356, NIH/NLM. For scientific research reference only. Not for human use.

Comparative Research Context — 2026 DACRA & Amylin Peptide Landscape

The comparison below summarizes chemical and receptor characteristics for laboratory research reference.

Feature	CAGRI (DACRA)	Pramlintide	GLP-1-Sm	GLP/GIP-Tz
Compound Class	Long-acting acylated amylin analogue + CTR agonist	Short-acting human amylin analogue	GLP-1 receptor agonist	Dual GLP-1/GIP agonist
Primary Receptor	AMY1R, AMY2R, AMY3R, CTR (DACRA)	AMY1R, AMY2R, AMY3R (AMYR-selective)	GLP-1R (hypothalamic)	GLP-1R + GIPR
Signalling Region	Area postrema / NTS (hindbrain)	Area postrema / NTS	Hypothalamic arcuate nucleus	Hypothalamic + peripheral
Half-Life	~159–195 h (~7 days)	~20–48 min	~7 days	~5 days
Fibril Formation	Minimised — 14E/17R + 25P/28P/29P modifications	Reduced (rat amylin scaffold)	N/A (non-amylin class)	N/A
Cryo-EM Structures	Available — all 4 receptor subtypes (Nature Comms 2025)	Limited structural data published	Published GLP-1R structures	Published GLP-1R/GIPR structures

Profound Amiono Supplier Quality Criteria (RUO)

Given CAGRI’s structural complexity — N-terminal lipidation, disulfide bridge, multi-position substitutions — standard HPLC purity alone is insufficient to verify research-grade quality. Three criteria, drawn from the analytical and regulatory guidance across the source documents, define minimum standards for credible RUO CAGRI research supply

1- LC-MS Identity Verification
HPLC purity confirms peptide content but cannot confirm lipidation completeness, disulfide bond formation, or sequence identity. LC-MS confirmation of full molecular weight (~4,409 Da) and sequence identity is required to distinguish intact CAGRI from the de-lipidated apo-peptide or from pramlintide/rat amylin — compounds that would produce different receptor pharmacology. Batch COA must include: HPLC purity (≥98%), LC-MS molecular weight confirmation, lot number, and stability conditions.

2-Cold-Chain and Storage Integrity
Lipidated peptide research compounds are sensitive to thermal degradation, oxidative stress, and hydrolysis of the fatty acid-peptide linkage. Lyophilised storage at −20°C or below under desiccated, light-protected conditions is required. Dissolved research solutions should be divided into single-use laboratory aliquots and stored at −80°C to prevent freeze-thaw degradation. Suppliers should document cold-chain maintenance from manufacture to laboratory delivery.

3-RUO Labelling Consistency — FDA Compliance Alignment
FDA warning letters (Summit Research Peptides Dec 2024; USApeptide.com Feb 2025) confirmed that RUO labels alone do not prevent enforcement when the totality of website and marketing evidence implies intended human use. [R22, R23] For CAGRI specifically, FDA (February 2026) confirmed the compound cannot be used in compounding under federal law. [R21] Suppliers must maintain strict RUO positioning consistently across product descriptions, communications, and all digital content.

REGULATORY & COMPLIANCE STATEMENT (RUO)

FOR RESEARCH USE ONLY. NOT FOR HUMAN OR ANIMAL APPLICATION.

Classification	Detail
Regulatory Status	Research Use Only (RUO) — U.S. Federal Framework
FDA Status	Supplied as a laboratory research compound. Not for use in humans or animals.
RUO Intended Use	Non-clinical laboratory research: receptor-binding studies, signalling pathway characterisation, laboratory metabolic models, SAR studies
Material Classification	Laboratory Reagent for research assays
Not a Supplement	Not a dietary supplement, nutraceutical, or consumer product
Compounding Prohibition	FDA confirmed (Feb 4, 2026) that Cagrilintide cannot be used in compounding under federal law — this remains unchanged as of August 2026. Separately, on April 30, 2026, FDA proposed not to include GLP-1-Sm , GLP/GIP-Tz , and liraglutide on the Section 503B Bulks List. The public comment period was extended to July 30, 2026, and FDA has not yet published a final determination as of this review.
Peptide Committee (PCAC)	Note: On July 23–24, 2026, FDA’s PCAC reviewed seven peptides (unrelated to Cagrilintide) for potential inclusion on the 503A Bulks List, recommending BPC-157, KPV, TB-500, MOTS-c, Epitalon, and Semax, and voting against emideltide. These recommendations are advisory and non- binding — FDA has not taken final action on them, and they do not affect Cagrilintide’s own regulatory status.
Intended Use Doctrine	RUO labels do not prevent FDA enforcement if marketing implies human use (FDA warning letters 2024–2025)
Google Ads Compliance	Product copy describes laboratory materials and assays without human-use claims
Google Search (March 2026)	Spam update targets AI-thin content and misleading health claims. E-E-A-T required
FTC Compliance	Health Products Guidance applies. Claims must be truthful, non-misleading, and scientifically supported
Safe Wording (FDA-aligned)	“Supplied solely for non-clinical laboratory research by qualified professionals. Not intended for use in humans or animals. No medical claims.”
Literature Framing	Published literature is informational and does not describe intended use
PPE / Lab Safety	Handle as bioactive compound. Use appropriate PPE and refer to SDS before use

RESEARCH USE ONLY: For laboratory research use only. Not for use in humans or animals. Refer to the SDS and applicable laboratory handling requirements.

For laboratory research use only. Not for use in humans or animals. Not intended to treat, cure, or prevent any disease.

Frequently Asked Questions

Q1: Is CAGRI intended for human or animal use?

No. Cagrilintide is strictly a Research Use Only (RUO) laboratory research compound. It is not approved, labelled, or intended for human or animal use, research outside laboratory settings, or any diagnostic application. Purchase confirms institutional laboratory research use only. Any human-use promotion violates U.S. federal law. [R21, R22, R23]

Q2: What is the difference between CAGRI and pramlintide?

Pramlintide is a short-acting amylin analogue with a reported half-life of approximately 20–48 minutes. CAGRI differs through N-terminal C20 fatty diacid lipidation, 14E/17R salt-bridge substitutions, and C-terminal proline. These structural features are studied in albumin-binding, stability, and receptor-selectivity assays. Cryo-EM data characterize CAGRI engagement across AMY1R, AMY2R, AMY3R, and CTR. [R3, R4, R5]

Q3: What analytical data is required per batch COA?

Research-grade batch COA for Cagrilintide requires: (1) RP-HPLC purity ≥98%; (2) LC-MS molecular weight (~4,409 Da) and sequence identity confirmation; (3) disulfide bridge formation confirmation; (4) lot number for traceability; (5) storage and stability conditions; (6) endotoxin screening (<1.0 EU/mg by LAL assay). LC-MS is non-optional given the structural complexity of Cagrilintide’s lipidation.

Q4: What solvent and storage conditions are described for laboratory research?

Aqueous buffers at pH 4.5–6.0 are described for laboratory stability studies. Dissolved research solutions are stored as single-use aliquots at −80°C to limit repeated freezing and thawing. Thiol-containing buffers, such as DTT, can affect DACRA redox chemistry, so laboratory studies should include appropriate redox controls.

Q5: How is this CAGRI material classified?

This CAGRI material is supplied as a Laboratory Reagent for receptor-binding, signalling, structural, and analytical research assays. For laboratory research use only. Not for use in humans or animals.

Q6: What cryo-EM structural data is available?

Bhatt et al., Nature Communications, vol. 16, article 3389 (April 2025; DOI:10.1038/s41467-025-58680-y; CC BY 4.0) resolved cryo-EM structures of Cagrilintide bound to Gs-coupled active AMY1R, AMY2R, AMY3R, and CTR simultaneously — the first full-receptor-complement structural dataset for any DACRA compound. Foundational AMYR structural basis: Liang et al., Science (2022), DOI:10.1126/science.abm9609. [R5, R6]

Q7: Does CAGRI’s pharmacology differ from salmon calcitonin (sCT)?

Yes — critically. RAMP1/3 knockout studies (Folgueira et al. 2025) showed Cagrilintide’s energy-balance effects depend on AMY1R and AMY3R, while sCT’s effects were paradoxically improved in RAMP1/3 KO models — indicating sCT operates through primarily CTR-dependent rather than AMYR-dependent mechanisms. These two DACRA compounds cannot be used interchangeably in receptor-specific research models despite both engaging CTR. [R8]

Q8: What is CAGRI’s position in the 2026 USA RUO peptide research market?

Cagrilintide occupies a narrow, high-value niche for amylin receptor pharmacology, DACRA biochemistry, and dual-pathway metabolic signalling research. The USA RUO regulatory environment has tightened substantially since 2024: intended-use doctrine applies regardless of disclaimers (R22, R23), and FDA has specifically named Cagrilintide as prohibited from compounding (R21). Businesses in this space must treat compliance as a primary operational requirement — not an afterthought. [R21–R23, R24, R25]

Q9: What is the intended laboratory research scope for CAGRI?

This material is supplied for laboratory receptor-binding, signalling pathway, structural, and analytical assays. Published animal-model studies provide scientific background and do not describe the intended use of this supplied material. Not for use in humans or animals. Follow applicable institutional laboratory safety requirements.

KEY REFERENCES : PubMed & Authoritative Sources (2024–2026)

All references are from primary peer-reviewed literature or official FDA and Google regulatory sources. No secondary aggregators were used. Regulatory status was reviewed through August 10, 2026.

Ref	Source	Type	Relevance
R12	Novo Nordisk Press Release — Dec 18, 2025 (prnewswire.com)	Corporate / Regulatory	NDA submission for CAGRI; REDEFINE programme; FDA review 2026
R14	Merrifield RB 1963 — J Am Chem Soc	Foundational Study	Solid-phase peptide synthesis (SPPS) — core method for research-grade manufacture
R15	Simon MD et al. 2014 — ChemBioChem (PMC4045704)	Primary Research	Flow-based SPPS enabling rapid coupling and higher-throughput RUO supply
R16	Mijalis AJ et al. 2017 — Nature Chem Biol (DOI:10.1038/nchembio.2318)	Primary Research	Fully automated flow-based SPPS — scalable peptide library production
R17	Hartrampf N et al. 2020 — Science (doi:10.1126/science.abb2491)	Primary Research	Fast-flow synthesis up to 164 amino acids; functional protein generation
R21	FDA — Feb 4, 2026	Regulatory	FDA research-material classification reference
R22	FDA Warning Letter — Dec 2024 (Summit Research Peptides 695607-12102024)	Regulatory Enforcement	RUO labelling does not shield from enforcement if human use is implied
R23	FDA Warning Letter — Feb 2025 (USApeptide.com 696885-02262025)	Regulatory Enforcement	Website content overrides RUO disclaimers — intended-use doctrine
R24	Google Ads Policy — Mar 2026 (Google Ads Help)	Platform Policy	Prohibits unapproved substances implying human outcomes; policy updated Mar 31, 2026
R25	Google Search — Mar 2026 (Search Central)	Platform / SEO	SpamBrain update: penalizes thin AI content, misleading health claims; E-E-A-T required

RESEARCH USE ONLY — NOT FOR HUMAN USE — NOT FOR ANIMAL USE