AstraZeneca Submits Clinical Trial Application in China for Second-Generation PRMT5 Inhibitor AZD3470
AstraZeneca
Biopharmaceutical Manufacturer
On November 20, the CDE website showed that the clinical trial application for AstraZeneca's second-generation PRMT5 inhibitor AZD3470 film-coated tablets has been accepted.
AZD3470 is a second-generation PRMT5 inhibitor that specifically targets the methylthioadenosine (MTA) and protein arginine methyltransferase 5 (PRMT5) complex, which can reduce adverse effects such as hematological toxicity caused by first-generation PRMT5 inhibitors and improve the therapeutic index.
As a post-translational modification enzyme, PRMT5 has been confirmed to be associated with various cancers. Studies have found that PRMT5 is overexpressed in multiple cancers, including glioblastoma, melanoma, leukemia/lymphoma, multiple myeloma, prostate cancer, bladder urothelial carcinoma, ovarian cancer, lung cancer, gastric cancer, and colorectal cancer, and is correlated with poor prognosis.
Inhibition or knockout of PRMT5 significantly reduces the ability of cell proliferation, migration, and colony formation, but promotes apoptosis and cell cycle arrest. Oral PRMT5 inhibitors demonstrate significant anti-tumor activity in lung tumor xenograft models.
Currently, five PRMT5 inhibitors have entered the clinical stage in China, namely AMG 193 (Amgen), SCR-6920 (Simcere Pharmaceutical), SH3765 (Shenghe Pharmaceutical), SYH2045 (Yishi Pharmaceutical), and SYHX2001 (Shiyao Group).
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