CRHR2/CRF2R ECD and Nanodisc Proteins

Corticotropin-releasing factor receptor 2, also known as CRFR2 or CRHR2, is a class B G protein-coupled receptor activated by corticotropin-releasing factor family peptides, particularly urocortins. Multiple receptor isoforms are generated through alternative splicing and show distinct tissue distributions. CRHR2 signaling contributes to the regulation of stress adaptation, cardiovascular function, energy balance, gastrointestinal activity, immune responses and autonomic physiology. Depending on the ligand, tissue and disease state, receptor activation can influence vascular tone, cardiac performance, feeding behavior, anxiety-related responses and inflammatory signaling. This broad physiology makes CRHR2 an attractive target for cardiovascular, metabolic, gastrointestinal and neuropsychiatric research, but it also creates challenges in separating beneficial tissue-specific effects from systemic endocrine or hemodynamic consequences.

Therapeutic development around CRHR2 remains largely preclinical. Investigated modalities include peptide agonists designed to enhance protective cardiovascular or metabolic signaling, small-molecule antagonists intended to suppress maladaptive stress pathways, and allosteric modulators that may provide greater signaling or tissue selectivity. Most work has focused on pharmacology, disease models and optimization of receptor-selective ligands rather than late-stage clinical development. Peptide stability, short systemic half-life, receptor-subtype selectivity and differences among CRHR2 isoforms have slowed translation. Published assessments indicate that no broadly established systemic CRHR2-specific therapy has yet emerged, although the receptor continues to be studied in heart failure, pulmonary and vascular disease, gastrointestinal disorders, stress biology and metabolic regulation. Better full-length antigens and binding assays are needed to support antibody discovery and clarify ligand–receptor pharmacology.

DIMA BIOTECH provides two complementary human CRHR2/CRFR2 protein formats for GPCR research and drug discovery. The portfolio includes a recombinant Human CRHR2 ECD Protein with a C-terminal human Fc tag, expressed in HEK293 cells, and a Human CRHR2-Strep Full-Length Protein presented in a synthetic Nanodisc, carrying C-terminal Flag and Strep tags. The Fc-tagged ECD protein provides a convenient format for antigen-based antibody screening, ligand–receptor interaction studies, ELISA, SPR, BLI, assay calibration and affinity analysis. The full-length Nanodisc protein preserves the intact seven-transmembrane architecture in a membrane-mimetic environment, making it particularly suitable for conformational antibody discovery, full-length receptor binding studies and GPCR-target validation. Its Flag and Strep tags also provide flexible options for protein capture, immobilization and detection. Together, the ECD and full-length Nanodisc formats allow researchers to compare extracellular-domain recognition with binding to the intact receptor, supporting antibody screening, ligand competition, assay development and early CRHR2-targeted therapeutic research.