AMG 193, a CNS-penetrant methylthioadenosine-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor, selectively induces synthetic lethality in MTAP-deleted tumor cells. Here, we report results of the completed monotherapy dose exploration evaluating AMG 193 in patients with MTAP-deleted solid tumors.

Jan 13, 2025 · We report the discovery of the clinical stage MTA-cooperative PRMT5 inhibitor AMG 193, which preferentially binds PRMT5 in the presence of MTA and has potent biochemical and cellular activity in MTAP-deleted cells across multiple cancer lineages.

Mar 27, 2025 · Herein, we report the discovery of MTA-cooperative PRMT5 inhibitor AMG 193, a molecule that inhibited the proliferation of HCT116 MTAP-deleted cells with ∼40x selectivity over HCT116 MTAP-WT cells. AMG 193 was orally efficacious in mouse xenografts of endogenous MTAP -null tumors such as BxPC-3 (96% TGI @ 100 mg/kg QD) and U87MG (88% TGI ...

Sep 16, 2024 · AMG 193 is a first-in-class, novel, MTA-cooperative PRMT5 inhibitor and a highly selective small molecule designed to specifically target MTAP-deleted cancer (Amgen Inc.). 3 In vitro, AMG 193 preferentially inhibited the MTA-bound PRMT5 enzyme in MTAP-null tumor cells.

Sep 16, 2024 · AMG 193, a CNS-penetrant methylthioadenosine-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor, selectively induces synthetic lethality in MTAP-deleted tumor cells. Here, we report results of the completed monotherapy dose exploration evaluating AMG 193 in patients with MTAP-deleted solid tumors.

Sep 16, 2024 · AMG 193 is a first-in-class, MTA-cooperative PRMT5 inhibitor that selectively targets MTAP -deleted tumors and spares normal cells, Sacher explained; because it preferentially binds...

Oct 13, 2023 · AMG 193 belongs to a class of compounds called MTA-cooperative PRMT5 inhibitors. These second-generation PRMT5 inhibitors are designed to suppress PRMT5 function specifically in MTAP-null cells while sparing it in healthy cells, thus selectively killing the tumor cells, Rodon explained.

Jun 2, 2022 · AMG 193 is an MTA-cooperative PRMT5i that preferentially targets the MTA-bound state of PRMT5 that is enriched in MTAP-null tumors and represents a novel strategy to increase the therapeutic margin of this class of inhibitors.

Dec 1, 2023 · In preclinical studies, AMG 193 demonstrated selective antitumor activity in MTAP-null models by further suppressing PRMT5 function while sparing normal function, thereby improving upon first generation molecules. We report the initial clinical results from dose-escalation in the ongoing first-in-human (FIH) study.

Dec 1, 2023 · In February 2022, AMG 193 became the first MTA-cooperative PRMT5 inhibitor to enter clinical development and is currently being evaluated in subjects with advanced MTAP-null solid tumors in the ongoing FIH study (NCT05094336).