Covalent-Allosteric Inhibitors: Do We Get the Best of Both Worlds?

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

Covalent-allosteric inhibitors (CAIs) may achieve the best of both worlds: increased potency, long-lasting effects, and reduced drug resistance typical covalent ligands, along with enhanced specificity decreased toxicity inherent in allosteric modulators. Therefore, CAIs can be an effective strategy to transform many undruggable targets into druggable ones. However, are challenging design. In this perspective, we analyze discovery known targeting three protein families: phosphatases, kinases, GTPases. We also discuss how computational methods tools play a role addressing practical challenges rational CAI

Язык: Английский

Warhead-bearing natural compounds for multi-pathway irreversible inhibition to overcome drug resistance in colorectal cancer

Medical Oncology, Год журнала: 2025, Номер 42(5)

Опубликована: Апрель 2, 2025

Язык: Английский