GPCR Specific Neutra™ Antibody Products

Are you facing prolonged drug development cycles or challenges in targeting GPCRs with high specificity? Creative Biolabs' GPCR-specific Neutra™ antibody products leverage advanced protein engineering and computational modeling to accelerate the identification of therapeutic candidates with superior binding affinity and functional precision.

Introduction to GPCR

G protein-coupled receptors (GPCRs) comprise the largest family of membrane-bound receptors in the human genome, with over 800 members regulating a variety of physiological functions, including neurotransmission, immune response, and hormone signaling. These receptors translate extracellular signals into intracellular responses via G proteins or β-arrestin pathways, making them prime targets for therapeutic intervention in diseases ranging from neurological disorders to cancer.

• Structural Complexity

GPCRs are characterized by a conserved seven-transmembrane α-helical architecture. The extracellular domain, including three extracellular loops (ECLs) and an N-terminus, mediates ligand binding, while intracellular regions interact with downstream signaling effectors. Structural flexibility allows GPCRs to adopt multiple conformational states (active, inactive, and intermediate), which dictate ligand efficacy and signaling bias.

• Signaling Pathways

GPCRs activate canonical Gαs, Gαi/o, and Gαq/11 pathways, modulating cAMP levels, calcium flux, and kinase cascades. Non-canonical β-arrestin-mediated signaling further regulates receptor internalization and gene expression. Dysregulation of these pathways contributes to pathologies such as hypertension, inflammation, and metabolic disorders. For example, overactive β-adrenergic receptors drive heart failure, while aberrant chemokine receptor signaling promotes cancer metastasis.

Fig.1 GPCRs signal through heterotrimeric G proteins.^1,3

• Disease Relevance

GPCRs are implicated in 30-40% of approved drugs, underscoring their therapeutic value. Neurological disorders (e.g., Alzheimer's, Parkinson's), cardiovascular diseases, and cancer frequently involve GPCR mutations or overexpression. In oncology, orphan GPCRs like GPR87 are overexpressed in lung and pancreatic cancers, driving tumor proliferation and chemoresistance. Targeting these receptors with neutralizing antibodies offers a path to disrupt pathogenic signaling without off-target effects.

Fig.2 Roles of GPCRs in tumorigenesis and therapeutic response.^2,3

Applications of GPCR Neutralizing Antibodies

• Precision Oncology

GPCR-neutralizing antibodies inhibit tumor growth by blocking pro-survival signaling. Anti-GPR87 antibodies, for example, reduce proliferation in lung squamous cell carcinoma models by interfering with lysophosphatidic acid (LPA)-mediated pathways.

• Neurological Disease Management

Antibodies targeting dopamine or serotonin receptors restore synaptic plasticity in neurodegenerative diseases. Preclinical studies demonstrate that anti-D2 receptor antibodies mitigate dyskinesia in Parkinson's models without systemic side effects.

• Metabolic Disorder Therapeutics

Glucagon-like peptide-1 receptor (GLP-1R)-specific antibodies enhance insulin secretion in type 2 diabetes, offering an alternative to peptide analogs with improved stability and dosing intervals.

• Infection and Inflammation Control

Antibodies against chemokine receptors (e.g., CCR5) prevent viral entry in HIV and suppress cytokine storms in autoimmune diseases.

• Diagnostic Development

GPCR antibodies enable biomarker detection in patient sera or tissue samples, aiding early diagnosis and personalized treatment strategies.

Our Anti-GPCR Antibody Products

Neutralizing GPCR antibodies require epitope specificity to extracellular domains (ECLs or N-terminus) to block ligand binding or receptor activation. Key attributes include:

- High Affinity: Nanomolar binding to overcome low receptor density on cell surfaces.

- Conformational Selectivity: Discrimination between active and inactive states to achieve signaling bias.

- Species Cross-Reactivity: Support translational studies in preclinical models.

Our antibodies are validated using cryo-EM and live-cell imaging to ensure target engagement and functional inhibition. For example, antibodies targeting ACKR3, a chemokine receptor, use longer CDR3 loops to trap the receptor in an inactive state, effectively inhibiting metastasis in vitro and in vivo.

Creative Biolabs' GPCR-specific Neutra™ antibody products combine structural precision and functional validation and are optimized for ELISA, flow cytometry, and in vivo models to advance your research programs.

Contact us to discuss your project requirements and receive customized solutions tailored to your objectives.

REFERENCES

1. Lynch, Jennifer R., and Jenny Yingzi Wang. "G protein-coupled receptor signaling in stem cells and cancer." International journal of molecular sciences 17.5 (2016): 707. https://doi.org/10.3390/ijms17050707
2. Zeng, Zhen, et al. "Roles of G protein-coupled receptors (GPCRs) in gastrointestinal cancers: focus on sphingosine 1-shosphate receptors, angiotensin ii receptors, and estrogen-related GPCRs." Cells 10.11 (2021): 2988. https://doi.org/10.3390/cells10112988
3. Distributed under Open Access license CC BY 4.0, without modification.