TED-347

TED-347 is a potent, irreversible, covalent and allosteric inhibitor at YAP-TEAD protein-protein interaction with an EC50 of 5.9 μM for TEAD4⋅Yap1 protein-protein interaction. TED-347 specifically and covalently bonds with Cys-367 within the central pocket of TEAD4 with a Ki of 10.3 μM. TED-347 blocks TEAD transcriptional activity and has antitumor activity[1].

Research Areas >> Cancer

Signaling Pathways >> Stem Cell/Wnt >> YAP

IC50: 5.9 μM (TEAD4⋅Yap1 protein-protein interaction)[1]

TED-347 (0.5-100 μM; 48 hours) inhibits GBM43 cancer cell viability[1]. TED-347 (5 μM; 48 hours) inhibits co-immunoprecipitation of Myc-tagged TEAD4 with FLAG-tagged Yap1[1]. TED-347 (10 μM; 48 hours) shows a significant reduction in CTGF transcript levels[1]. TED-347 (0.5-100 μM; 24 hours) reduces reporter activity in cells transfected with a TEAD reporter. TED-347 (0.5-100 μM) also inhibits TEAD4 transcriptional activity in GBM43 cells[1]. TED-347 is selective for TEADs and inhibits TEAD2 with the same efficacy. TED-347 (0.1-100 μM; 24-48 hours) inhibits TEAD4 binding to full-length Yap1 in dose- and time-dependent manner. TED-347 (1-100 μM) shows no inhibition of uPAR•uPA or Cav2.2 α•β protein-protein interactions. Non-covalent binding of TED-347 to TEAD4 exhibits little change to the TEAD4•Yap1 binding affinity[1]. TED-347 has the maximum rate of inactivation of 0.038 hours, corresponding to a t1/2∞ of 18.2 hours[1]. Cell Viability Assay[1] Cell Line: GBM43 glioblastoma cell lines Concentration: 0.5, 1, 10, 100 μM Incubation Time: 48 hours Result: Inhibited GBM43 cancer cell viability and inhibited GBM43 cell viability by 30% at 10 μM. Western Blot Analysis[1] Cell Line: HEK-293 cells Concentration: 5 μM Incubation Time: 48 hours Result: Showed a significant loss of co-immunoprecipitation of Myc-tagged TEAD4 with FLAG-tagged Yap1. RT-PCR[1] Cell Line: HEK-293 cells Concentration: 10 μM Incubation Time: 48 hours Result: Showed a significant reduction in CTGF transcript levels versus control cells and had no inhibition on TEAD mutant transcriptional activity and protein-protein interactions in cell culture.

[1]. Khuchtumur Bum-Erdene, et al. Small-Molecule Covalent Modification of Conserved Cysteine Leads to Allosteric Inhibition of the TEAD⋅Yap Protein-Protein Interaction. Cell Chem Biol. 2019 Mar 21;26(3):378-389.e13.