IAG933

IAG933 is an inhibitor of the protein-protein interaction between YAP/TAZ and TEAD (IC50 = 8.6 nM in a TR-FRET assay), downstream effectors of Hippo/MST1/2 signaling, which regulates cell proliferation and is frequently dysregulated in cancer. It reduces growth of Hippo-dependent NCI-H2052 mesothelioma cells and YAP-amplified SF-268 glioma cells (GI50s = 0.04 and 1.11 nM, respectively) but not Hippo-insensitive MKN45 gastric cancer cells (GI50 = >10 nM). Oral administration of IAG933 (30 mg/kg) induces tumor regression in a Hippo-driven MSTO-211H mesothelioma rat xenograft model.. SMILES: ClC([C@]([C@](C(F)=C(N=C1)OCCO)=C1C(NC)=O)=C2C3)=C(C=C2O[C@]3([C@H]4NCCC4)C5=CC=CC=C5)F. InChi Code: InChI=1S/C27H26ClF2N3O4/c1-31-25(35)17-14-33-26(36-11-10-34)24(30)22(17)21-16-13-27(20-8-5-9-32-20,15-6-3-2-4-7-15)37-19(16)12-18(29)23(21)28/h2-4,6-7,12,14,20,32,34H,5,8-11,13H2,1H3,(H,31,35)/t20-,27-/m0/s1. InChi Key: HUVOYQMXUNTUAI-DCFHFQCYSA-N