Structure-Activity Relationship Study of 3-Alkynyl-6-aryl-isothiazolo[4,3-<i>b</i>]pyridines as Dual Inhibitors of the Lipid Kinases PIKfyve and PIP4K2C.

ABSTRACT: Background/Objectives: RMC-113, a 3-alkynyl-6-aryl-disubstituted isothiazolo[4,3-b]pyridine, is a dual inhibitor of the lipid kinases PIKfyve and PIP4K2C with broad-spectrum antiviral activity. The aim was to study the structure-activity relationship (SAR) of isothiazolo[4,3-b]pyridines as dual PIKfyve/PIP4K2C inhibitors. Methods: A series of isothiazolo[4,3-b]pyridines was synthesized by introducing structural variety at positions 3 and 6 of the central scaffold. The primary assay to guide the synthetic chemistry was a biochemical PIKfyve assay, with a number of analogues also tested for PIP4K2C binding affinity. Finally, isothiazolo[4,3-b]pyridines were also evaluated for antiviral and antitumoral activity in cell-based assays. Results: PI

SUBMITTER: Kalebic D 

PROVIDER: S-EPMC12472322 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature