Fig. 5: Chemical synthesis and characterization of TEAD inhibitors. | Nature Communications

Fig. 5: Chemical synthesis and characterization of TEAD inhibitors.

From: Targeting TAZ-TEAD in minimal residual disease enhances the duration of targeted therapy in melanoma models

Fig. 5

A The steps in the chemical synthesis of OPN-9643. B The steps in the synthesis of OPN-9652. C Results of MSTO-211H reporter assay IC50 values, NCI-H226 growth IC50 values, and Delta Tm TEAD1/TEAD4 protein thermal shift values following OPN-9643 and OPN-9652 treatment. D Co-crystal structure of OPN-9652 bound to TEAD1 (PDB ID: 8S6Y). OPN-9652 occupies the central palmitate-binding pocket and covalently modifies Cys359. Image on the left shows an overlay of OPN-9652 (gold) and palmitate (green). Image on the right shows a zoomed-in view covalent modification of Cys359 (mint) by OPN-9652 (gold).

Back to article page