GPCR-Targeted Therapy

Online Inquiry

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G-protein coupled receptors (GPCRs) are important transmembrane proteins superfamily, accounting for 4% of the human genome. The structure of a GPCR typically consists of an extracellular N-terminus linked to seven α-helical transmembrane domains (TMDs) with an intracellular C-terminus. Within the TMD, several motifs are highly conserved with GPCR subfamilies, but the homology between these subfamilies is very limited.

GPCRs play key roles in tissue and cellular physiology, as well as homeostasis. They are implicated in various diseases, including cancer, immune-mediated inflammatory diseases, cardiovascular diseases, infectious diseases, neurological diseases, and metabolic diseases. Approximately 800 GPCRs are known, about 370 of which reveal drug targeting capabilities.

Anti-GPCR Antibody Therapy

Currently, small-molecule drugs are developed to target only a limited proportion of GPCRs. Thus, receptors may be better targeted by antibody-based therapeutics rather than small molecules when given the size of the ligand-binding pocket. The mechanisms of action afforded by antibody-based therapeutics include antagonism (or blocking), agonism (or activating), receptor modulation, as well as other functional effects specifically mediated by the Fc region (such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cell-mediated phagocytosis (ADCP)).

In the field of drug development that targets GPCRs, antibodies have revealed unique advantages over small molecule drugs:

• Superior selectivity and the potential for different mechanisms of action, such as antibody-drug conjugates (ADC), bispecific or multi-specific targeting;
• Improved pharmacokinetic (PK) & pharmacodynamic (PD) properties due to a more favorable biodistribution, superior half-life with less patient PK variability;
• Higher selectivity, reduced side effects (especially the central nervous system) and dose regimens.

Project Overviews

Drug discovery targeting GPCRs remains challenging. However, there are a number of startups that use innovative technology platforms to develop small molecules and therapeutic antibodies targeting challenging or previously undruggable GPCRs.

At Protheragen, we help out-license and find co-development opportunities for GPCR-targeted therapeutics in the early stages of development. If you are interested in any of these projects, please contact us for further discussion. We look forward to our collaboration.

Collaboration Opportunity

Protheragen is actively seeking partners to develop these GPCR-targeted therapeutics further. Potential collaboration can be a strategic alliance, licensing, or marketing agreement.