Mobocertinib succinate (TAK-788) is a potent, mutant-selective, irreversible inhibitor of EGFR ex20ins mutations with IC50 of 2.7 to 22.5 nM.
Mobocertinib (TAK-788) displays selectivity over WT EGFR (IC50=34.5 nM).
Mobocertinib (TAK-788) inhibited all five variants of EGFR ex20ins mutations with IC50 of 4.3 nM for NPG, 10.9 nM for ASV, 11.8 nM for A763_Y764insFQEA (FQEA), 18.1 nM for N771_H773dupNPH (NPH), and 22.5nM for S768_D770dupSVD.
Mobocertinib (TAK-788) inhibited viability of various EGFRex20ins-driven cell lines more potently (CUTO14 cell viability assay, IC50=33 nM) than approved EGFR TKIs and demonstrated in vivo antitumor efficacy in patient-derived xenografts and murine orthotopic models.
