K-975

K-975 is a potent, selective and orally active TEAD inhibitor, with a strong inhibitory effect against protein-protein interactions between YAP1/TAZ and TEAD. K-975 covalently binds to Cys359 located in the palmitate-binding pocket of TEAD via an acrylamide structure. K-975 exhibits antitumor activity on malignant pleural mesothelioma In Vitro K-975 (0.1-10000 nM; 144 h) inhibits the cell proliferation of NF2-non-expressing malignant pleural mesothelioma (MPM) cell lines. K-975 (10-10000 nM; 24 h) inhibits protein-protein interaction (PPI) between Halo-YAP and endogenous TEAD1/4 and Halo-TAZ and TEAD1/4 in NCI-H226 cells. K-975 (0.1-10000 nM; 24 h) strongly inhibits the reporter activity in NCI-H661/CTGF-Luc cells, with the maximum inhibition of ~70%, and does not inhibit the reporter activity in NCI-H661/NRF2-Luc cells. K-975 (1-10000 nM; 24 h) decreases the expressions of CTGF , IGFBP3 , and NPPB mRNAs, and increases the expression of FBXO32 mRNA in NCI-H226 cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: NF2-non-expressing MPM and NF2-expressing malignant MPM cells Concentration: 0.1, 1, 10, 100, 1000, 10000 nM Incubation Time: 144 hours Result: Had a stronger inhibitory effect against NF2-non-expressing cell lines than NF2-expressing cell lines. Inhibited the proliferation of MSTO-211H cells, an NF2-expressing cell line. Western Blot AnalysisCell Line: NCI-H226 cells Concentration: 10, 100, 1000, 10000 nM Incubation Time: 24 hours Result: Inhibited TEAD1-YAP1 PPI and TEAD4-YAP1 PPI. Inhibited TEAD1-TAZ PPI and TEAD4-TAZ PPI. In Vivo K-975 (10-300 mg/kg; p.o. twice a day for 14 days) inhibits the tumor growth by inhibiting YAP1/TAZ-TEAD signaling in MPM xenograft mouse models . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male SCID mice (5 weeks) injected with NCI-H226 or MSTO-211H cells Dosage: 10, 30, 100, 300 mg/kg Administration: P.o. twice a day for 14 days Result: Exhibited strong anti-tumor effect in MPM s.c. xenograft mouse models. Decreased the expressions of CTGF , IGFBP3 , and NPPB , and increased the expression of FBXO32 in the NCI-H226 xenograft model. IC50& Target:TEAD

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