Emerging Tumor Target – GSPT1
Kyinno Biotechnology, Inc.
A preclinical CRO drives progress in cancer research and drug discovery
On October 8, 2024, Cullgen announced that its self-developed GSPT1 degrader CG009301 has received approval from the National Medical Products Administration (NMPA) of China, entering the clinical research phase for the treatment of relapsed or refractory hematologic malignancies. This news marks an important step forward in the application of the emerging target GSPT1 in the field of precision medicine.
The GSPT1 gene encodes the eukaryotic release factor eRF3a, which plays a critical role in the translation termination process of protein synthesis. It works in conjunction with the eRF1 protein to recognize the stop codons on messenger RNA (mRNA), promoting the release of the nascent polypeptide from the ribosome, thereby terminating protein translation. This process is vital for the normal function of cells.
In addition to translation termination, GSPT1 is involved in other cellular processes, including nonsense-mediated mRNA decay (NMD), a mechanism crucial for mRNA quality control. In cancer research, increasing evidence suggests that GSPT1 is overexpressed in various cancers, and its upregulation is directly associated with poor prognosis. By inhibiting GSPT1, apoptosis can be induced in cancer cells, reducing their viability, making GSPT1 a potential therapeutic target.
In recent years, scientists have gained a deeper understanding of the role of GSPT1 in cancer initiation and progression. GSPT1 not only regulates the cell cycle but also participates in cellular responses to genotoxic stress. Given its broad biological functions, therapeutic strategies targeting GSPT1 are rapidly advancing.
Cullgen's CG009301 is based on these cutting-edge scientific developments. As a highly selective GSPT1-targeting protein degrader, CG009301 induces the degradation of GSPT1 protein, thereby blocking its critical function in cancer cells and inhibiting tumor growth. This innovative molecular mechanism shows great potential in treating relapsed or refractory hematologic malignancies such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and high-risk myelodysplastic syndromes (MDS).
To support the development of GSPT1-targeted drugs, Kyinno has established GSPT1-HiBiT cell lines constructed using CRISPR-Cas9 technology, including 293T-GSPT1-HiBiT-KI(+/-)-LgBiT-OE, for the evaluation of GSPT1 degradation drugs. The validation data is as follows. Please feel free to contact us for more information.
Cell Line Table:
CRBN Degrader SJ6986 Induces Degradation of GSPT1-HiBiT:
领英推荐
HIBIT Signal Validation:
Sequencing Validation Results:
References:
Dandan Zhang, Pei Lin, Jun Lin. Molecular glues targeting GSPT1 in cancers: A potent therapy.
Ivanov, I. P., & Atkins, J. F. (2000). Ribosome Stalling and Peptide Release during Translational Termination. Molecular Cell, 6(5), 973-984.
Inada, T., & Aiba, H. (2005). Mechanisms Regulating Translational Termination in Eukaryotes. Progress in Nucleic Acid Research and Molecular Biology, 79, 1-47.