Professional technology integration to support the entire R&D process

1. TSHR as a Critical Target in Thyroid Cancer Therapy

Over the past decade, the global incidence of thyroid cancer has risen significantly, with Differentiated Thyroid Cancer (DTC) accounting for 96% of cases. While standard treatments include surgical resection, TSH suppression, and radioactive iodine therapy, the Thyroid-Stimulating Hormone Receptor (TSHR) has emerged as a groundbreaking target for innovative DTC therapies.

As a G-protein coupled receptor (GPCR) located on the surface of thyroid cells, TSHR plays a pivotal role in regulating thyroid hormone synthesis and secretion by activating the Gs signaling pathway upon binding with TSH.

2. Understanding TSHR Structure and Signaling Pathways

To facilitate drug mechanism of action (MoA) studies, our models focus on the three key domains of the TSHR protein:

• Extracellular Domain (ECD): Contains 418 hydrophilic amino acids, including leucine-rich repeats (LRR) and a hinge region for TSH binding.
• Transmembrane Domain (TMD): Consists of seven helical segments mediating signal transduction.
•  Intracellular Domain (ICD): Interacts with G-proteins to initiate downstream signaling.

Key Signaling Pathways:

1. Gs Pathway: Increases cAMP levels and activates PKA, regulating thyroid peroxidase (TPO) and the sodium/iodide symporter (NIS).

2. Gq Pathway: Activates phospholipase C (PLC), influencing cell survival, proliferation, and metabolic processes.

3. Landscape of TSHR-Targeted Drug Development

Approved Drugs Several TSHR-targeted therapies have successfully received market approval:

• Recombinant human thyroid stimulating hormone(SmartNuclide)
• Thyrotropin Alfa(Sanofi)

Recombinant human thyrotropin (Suzhou Zelgen Biopharmaceuticals Co., Ltd.)

TSHR Drug Development Pipeline

4.Reqbio TSHR Cell Models: A Reliable Platform for Accelerated Drug R&D

HEK293 Human TSHR CRE-Luc Cell Line (Cat No. RQP71485)

The TSHR CRE-Luc HEK293 cell model developed by Reqbio stably expresses the TSHR receptor and is suitable for:

• High-Throughput Screening (HTS)
• Agonist Dose-Response Profiling
• Signaling Pathway Mechanism Analysis

The model utilizes a luciferase reporter gene system to intuitively detect TSHR signaling pathway activation, providing quantitative data for precise drug activity assessment.

Figure 3. Recombinant TSHR CRE-Luc HEK293 stably expressing TSHR.

Figure 4. Dose Response of Agonists in TSHR CRE-Luc HEK293(C31).

CHO-K1 Human TSHR Cell Line (Cat No. RQP71474)

The CHO-based TSHR model offers the following advantages:

• High Receptor Expression
• Stable Performance
• HTRF cAMP Compatibility

This model directly measures cAMP level fluctuations via HTRF technology, providing direct evidence for TSHR functional studies.

Figure 5. Recombinant TSHR CHO-K1 stably expressing TSHR.

Figure 6.  HTRF cAMP Assay with TSHR CHO-K1(C11).

5. The Critical Role of Reporter Gene Cell Models in Drug R&D

Reporter gene cell models have become indispensable tools in modern drug development due to their unique advantages:

Core Advantages

1.Mechanistic Relevance: Accurately reflects the drug molecule's mechanism of action (MoA).

2.Data Stability: Low coefficient of variation (CV) with high reproducibility.

3.Operational Convenience: Optimized for high-throughput screening (HTS) and automated workflows.

4.High Standardization: Adopted by the National Institutes for Food and Drug Control (NIFDC) and leading pharmaceutical enterprises.

Application Scenarios

• Antibody Bioactivity Assays
• Lead Discovery & Optimization
• Quality Control (QC)
• Batch Release Testing

6. Reqbio Technology Platforms & Services

As a professional provider of drug screening cell models, Renkuan Biotech possesses:

Core Technology Platforms

• Advanced Cellular Functional Modification
• High-Precision Gene Editing Tools
• Flexible Custom Development

Product Portfolio

Reqbio currently offers an extensive catalog of over 1,500 ready-to-use cell models:

• Kinase Target Models
• GPCR Receptor Models
• Immunotherapy-Related Models
• Drug Resistance Research Models

Professional Services

• Cell-Based Bioassay Services
• Custom Cell Model Development
• Drug Screening Protocol Design
• Data Analysis & Interpretation Support

7. Conclusion

As a pivotal target in thyroid cancer therapy, TSHR-related drug development is currently entering a phase of rapid acceleration. High-quality TSHR cell models serve as indispensable tools for drug discovery, mechanism of action (MoA) research, and preclinical evaluation.

Reqbio, leveraging its professional technology platforms and extensive product portfolio, is committed to providing reliable TSHR research solutions to global research institutions and biopharmaceutical companies. Together, we strive to drive innovative breakthroughs in the field of thyroid cancer therapy and improve patient outcomes.