Structure-guided design of a methyltransferase-like 3 (METTL3) proteolysis targeting chimera (PROTAC) incorporating an indole–nicotinamide chemotype
Annabelle C. Weldert, Ariane F. Frey, Mackenzie W. Krone, Franziska Krähe, Hannah Kuhn, Christian Kersten, Fabian Barthels
Abstract
A level reduction in cancer cells than its non-PRTOAC parent compounds. By incorporating the indole-nicotinamide chemotype as the METTL3-binding recruiter, this PROTAC is structurally distinct from recently published METTL3 PROTACs, expanding the design options for future METTL3 degrader development.
Topics & Concepts
ProteolysisChimera (genetics)Indole testChemotypeComputational biologyChemistryBiologyStereochemistryBiochemistryEnzymeGeneChromatographyEssential oilProtein Degradation and InhibitorsCancer-related gene regulationUbiquitin and proteasome pathways