Although tricomplex pan-RAS (ON) inhibitors, such as RMC-6236, constitute a promising class of therapeutics against RAS-driven cancers, their on-target, off-tumor toxicities challenge the dosing strategy and the safety of drug combinations.
Inactivation of the tumor suppressor p53 occurs in approximately half of human cancer cases. In particular, the Y220C point mutation, which induces p53 misfolding and inactivation, is found in about 1% of solid tumors. Previous research identified a unique, druggable pocket on the p53 surface created by this mutation that constitutes a promising cancer therapeutic target.
Type I protein arginine methyltransferases (PRMTs) are an attractive target for inhibiting growth of triple-negative breast cancer. Several small-molecule inhibitors of these enzymes are in various stages of preclinical development, while clinical trials of the inhibitor GSK-3368715 had to be terminated early because of poor efficacy and toxicity.
Researchers from Prospect Therapeutics Inc. have discovered PSTA-5204, a novel oral KRAS G12D(ON) inhibitor that exhibits potent in vitro activity, strong in vivo efficacy and high selectivity over wild-type KRAS.
Aurigene Oncology Ltd. recently provided details on the discovery and preclinical characterization of AUR-243, a novel CBL-B inhibitor with a distinct therapeutic profile and best-in-class potential compared to other inhibitors. AUR-243 was described as a structurally distinct, oral small molecule demonstrating excellent potency, functional activity and superior efficacy.
Researchers at Triana Biomedicines Inc. presented the preclinical characterization of TRI-611, a CNS-penetrant molecular glue degrader targeting ALK in models of ALK fusion-positive non-small-cell lung cancer.
Researchers from Chemdiv Inc. and Eilean Therapeutics LLC recently presented preclinical data on ZE77-0273, an AI-designed, reversible pan-EGFR inhibitor developed to address a key unmet need in the treatment of EGFR-mutant non-small-cell lung cancer.
Prospect Therapeutics Inc.’s PSTA-2413 is a newly developed oral pan-RAS inhibitor that demonstrates selectivity over wild-type KRAS, along with strong in vitro potency and in vivo antitumor efficacy.
Loss of FOCAD in cells impairs normal mRNA surveillance, creating a dependency on the HBS1L/PELO complex for ribosome rescue and identifying HBS1L as a potential synthetic lethal target and therapeutic vulnerability.
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