Cagrilintide

Storage. Store dry solid desiccated at -20^°C to -80^°C, protected from atmospheric moisture and direct light.

Solubility. Soluble in sterile laboratory-grade deionized water (≥ 10 mg/mL), sterile Phosphate-Buffered Saline (PBS, pH 7.4), or slightly alkaline aqueous buffers (pH 7.5–8.0) for in vitro assay stock delivery.

• Handling & Disulfide Preservation: Contains an intramolecular cyclic disulfide bridge (Cys²–Cys⁷) and a lipophilic acylated diacid chain; exclude reducing agents (e.g., DTT, TCEP) from assay diluents to preserve tertiary loop structure, avoid vigorous mechanical agitation, and store single-use aliquots at -20^°C to eliminate freeze-thaw cycles.

Non-selective, potent dual agonist of the Calcitonin Receptor (CTR) and Amylin Receptor subtypes (AMY₁, AMY₂, and AMY₃), which consist of the CTR core complexed with Receptor Activity-Modifying Proteins 1, 2, or 3 (RAMP1/2/3).

Structural Engineering & Fibril Resistance: Engineered to address native human amylin's high propensity for spontaneous β-sheet amyloid fibril aggregation in solution. Incorporates specific proline substitutions at positions 25, 28, and 29 to disrupt β-sheet stacking, while an engineered salt bridge (Glu¹⁴–Arg¹⁷) stabilizes the α-helical domain. The conjugated C20 diacid tail promotes high-affinity reversible binding to albumin in biochemical assay media.

Cellular Pathways Investigated: Evaluated in preclinical receptor-transfected cell lines (e.g., CHO or HEK293 expressing human CTR/RAMP complexes) to quantify intracellular cAMP accumulation, pERK1/2 phosphorylation, and downstream signal transduction kinetics.