G-protein-coupled receptors (GPCRs) play a vital role in biology and medicine, but only a small number of them have drugs that target them. Tanso Biosciences has developed a versatile and sensitive assay method to overcome the challenges in GPCR research and promote drug development (Patent Publication Number WO/2020/026979). This innovative platform enables the company to engage in drug discovery for orphan GPCRs and offer contract assay services.

Comprehensive Orphan GPCR Drug Discovery Project

Research on GPCRs, especially orphan GPCRs, has been hindered by a lack of adequate assays. To overcome the barriers of GPCR drug discovery, we have innovated a high-performance functional assay. It works excellently for all receptors coupled with any of the major Gα proteins including Gq, Gs, Gi/o, and G12/13.

We have taken advantage of our proprietary assay and embarked on orphan GPCR drug discovery, broadly targeting ~100 of them. As a first step, compound library screening is ongoing for their agonists, with a priority on disease-associated receptors.

We have identified agonists for six orphan GPCRs, namely, GPR39, GPR55, GPR65, GPR68, GPR132, and P2RY10, and characterized their concentration-dependent potency.

Agonists identified in the previous step will be further characterized. They will also play crucial roles in screening for orphan GPCR antagonists.

Tanso Biosciences provides super-sensitive and reliable functional assays for more than 550 human and mouse G-protein-coupled receptors (GPCRs) to expand frontiers, accelerate drug discovery, and reduce R&D risks.

Assay Line-Up

Besides assays illustrated here, we can arrange various tests, such as allosteric modulation and GPCR homologs in other species than human.

Large-Scale Comprehensive Panels

Our large-scale panel assays allow comprehensive screening for up to 294 human GPCRs and >250 mouse GPCRs.

Example

Safety Panels

GPCR Safety Panels are designed to help evaluate the off-target potency of candidate compounds in drug discovery and preclinical research. These panels include GPCRs often linked with common adverse reactions, making them a practical resource for pharmaceutical R&D. 

• Standard GPCR Safety Panel: Features a minimal set of 24 representative GPCRs, allowing for testing compounds in both agonistic and antagonistic modes.
• GPCR Safety Panel Premium: Includes 31 additional GPCRs from the same receptor families for broader coverage.

See the panel assay page for details.

FlexPanel48

FlexPanel48 is reasonable small-scale panels with 48 receptors and consists of custom panels and therapeutic area panels.

Custom Panels

One can choose any 48 receptors from >550 human/mouse GPCRs.

Therapeutic Area Panels

Panels of 48 GPCRs associated with one of 13 therapeutic areas.

Example

TAK-875, a Phase 3 antidiabetic, was screened in the agonist mode in the FlexPanel48 Endocrinology/Metabolism Panel. The agent selectively activated free fatty acid receptor 1 (FFAR1).

Concentration Dependence

We analyze concentration dependence n various assay modes (agonist, inverse agonist, antagonist, PAM, NAM) and are flexible in study design, such as the numbers of replicates and concentrations.

Examples

TAK-875, a Phase 3 antidiabetic, was shown to activate FFAR1 in a concentration-dependent manner.

Inter-Species Analysis

Some GPCRs demonstrate remarkable inter-species differences in their activities and sensitivity to ligands.

Examples

We investigated the sensitivity of human and mouse GPCRs to various agonists and antagonists. We found that WKYMVM had similar agonistic effects on both human and mouse FPR1. However, the agonist fMLP exhibited significantly greater potency against human FPR1 compared to the mouse ortholog (first two panels). Additionally, human and mouse C5AR1 responded differently to the ligands C5a and avacopan (last two panels).

Proton-Sensing GPCRs

Examples