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

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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

Language: Английский

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

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(5)

Published: April 2, 2025

Language: Английский