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Liu, Yanfen et al., Routes to molecular glue degrader discovery, TIBS, Volume 50, Issue 2, 134 – 142

Genosco's TPD/MGD program is based on an innovative approach that utilizes Targeted Protein Degradation (TPD) and Molecular Glue Degrader (MGD) technologies to eliminate proteins that are difficult to target with traditional drug development methods. The program aims to successfully target undruggable proteins and develop therapies for various diseases.

The TPD/MGD program at Genosco also focuses on developing innovative therapies by combining Targeted Protein Degradation (TPD) technology with Antibody-Drug Conjugate (ADC) technology using DAC (Degrader-Antibody Conjugate) technology. Specifically, DAC is designed to selectively act on certain cancer cells by conjugating an MGD (Molecular Glue Degrader) that targets GSPT1 to an antibody. This approach is expected to offer higher selectivity and efficacy compared to traditional ADCs that use cytotoxic drugs. The DACs developed based on Genosco's candidate compounds have demonstrated remarkable efficacy in various solid tumors and are expected to provide new therapeutic options that overcome the limitations of existing therapies through further research.

The main candidate compound currently being developed under Genosco's TPD/MGD program targets MYC-related cancers, focusing on GSPT1, a protein that regulates tumor growth and survival. The current candidate compound is a Molecular Glue Degrader (MGD) that works by degrading proteins that are difficult to target with conventional small molecule drugs, thereby inhibiting the progression of MYC-driven cancers. MGDs link target proteins with E3 ligases, leading to the degradation of these proteins via the ubiquitin-proteasome system. Unlike traditional inhibitors, this approach effectively removes problematic proteins within the cell.

The candidate compounds developed on the GENO-D platform are currently in preclinical research. The preclinical results have shown that the candidate compound successfully inhibits cell survival through effective GSPT1 degradation in MYC-overexpressing cancer cells. These findings suggest that Genosco's candidate compound holds strong therapeutic potential for MYC-driven cancers, and preparations are underway for clinical trials. Additionally, further molecular glue candidates are being explored to expand the range of targets to include other undruggable proteins.

MYC-driven cancers include various types of cancer caused by the overexpression of the MYC gene, which plays a crucial role in tumor formation. MYC is a transcription factor essential for cell growth, division, and metabolic regulation, and has a significant impact on the development and progression of cancer. However, MYC is challenging to target with conventional small molecule drugs due to the lack of a binding pocket. Genosco's TPD/MGD program aims to provide a therapeutic effect for MYC-driven cancers by using MGDs to degrade proteins associated with MYC. This approach represents a significant innovation that could offer new hope to patients for whom conventional therapies have been limited.