Insilico Medicine Cayman Topco has nominated ISM-0387, an MTA-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor, as a preclinical developmental candidate for glioblastoma. The discovery and optimization process for ISM-0387 was powered by Chemistry42, Insilico’s generative chemistry platform integrated with over 40 generative AI models.
Homozygous deletion of methylthioadenosine phosphorylase (MTAP), present in ~15% of tumors, leads to accumulation of methylthioadenosine and partial inhibition of protein arginine methyltransferase 5 (PRMT5), creating a synthetic-lethal vulnerability that sensitizes tumors to PRMT5-targeted therapies. Researchers from Beone Medicines Ltd. presented preclinical efficacy data of BGB-58067, an MTA-cooperative PRMT5 inhibitor, in models of tumors with MTAP-deficiency.
Researchers from Jiangsu Hengrui Pharmaceuticals Co. Ltd. and Shanghai Hengrui Pharmaceutical Co. Ltd. have synthesized new protein arginine N-methyltransferase 5 (PRMT5) inhibitors reported to be useful for the treatment of cancer.
Alicorn Pharmaceutical Co. Ltd. has described protein arginine N-methyltransferase 5 (PRMT5) inhibitors reported to be useful for the treatment of cancer.
Researchers from Tango Therapeutics Inc. presented preclinical efficacy data on TNG-456, a selective MTA-cooperative PRMT5 inhibitor under development for the treatment of glioma and other tumors that frequently metastasize to the brain, such as non-small-cell lung cancer.
Shanghai Apeiron Biotechnology Co. Ltd. has divulged protein arginine N-methyltransferase 5 (PRMT5) inhibitors reported to be useful for the treatment of brain metastatic cancer.
In glioblastoma multiforme, MTAP loss leads to MTA accumulation, which partially inhibits PRMT5, making the cells reliant on residual PRMT5 activity for survival. Targeting this remaining PRMT5 with MTA-cooperative inhibitors induces synthetic lethality, representing a promising targeted approach for MTAP-deleted gliomas. Researchers from Ryvu Therapeutics SA reported the preclinical profile of RVU-305, a PRMT5 inhibitor, in MTAP-deleted cancer models.
China Resources Pharmaceutical Research Institute (Shenzhen) Co. Ltd. has disclosed heterocyclic compounds acting as protein arginine N-methyltransferase 5 (PRMT5) inhibitors reported to be useful for the treatment of cancer.
Tango Therapeutics Inc. plans a pivotal study next year in second-line MTAP-deleted pancreatic ductal adenocarcinoma based on positive phase I/II data with next-generation MTA-cooperative PRMT5 inhibitor vopimetostat (TNG-462) in patients with tumors of that type.
Work at Pharmaengine Inc. has led to the identification of new protein arginine N-methyltransferase 5 (PRMT5) inhibitors reported to be useful for the treatment of cancer.
