Mobocertinib (TAK-788) succinate is an orally active and irreversible EGFR/HER2 inhibitor. Mobocertinib succinate potently inhibits oncogenic variants containing activating EGFRex20ins mutations with selectivity over wild-type EGFR . Mobocertinib succinate can be used in NSCLC research
In Vitro
Mobocertinib succinate (1.5 nM-10 μM; 7 days) inhibits LU0387 (NPH) cells with IC 50 of 21 nM. Mobocertinib succinate (2 h) potently inhibits EGFR with common activating mutations (HCC827 (D), HCC4011 (L)) or with a T790M mutation (H1975 (LT)) more potently than WT EGFR (A431 (WT)). Mobocertinib succinate (0.1 nM-1 μM; 6 h) inhibits pEGFR and pERK1/2 in CUTO14 (ASV) cells. Mobocertinib succinate (0.3 nM-1 μM; 6 h) inhibits EGFR and downstream signaling. Mobocertinib succinate (0.01, 0.1 and 1 μM; 6 h) inhibits HER2 signaling in H1781 (HER2 Exon 20 G776>VC ), Ba/F3 (HER2 exon 20 YVMA ) cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: LU0387 (NPH) cells Concentration: 1.5 nM-10 μM Incubation Time: 7 days Result: Showed good inhibition activity for LU0387 (NPH) cells with IC 50 of 21 nM. Cell Viability AssayCell Line: A431 (WT), HCC827 (D), HCC4011 (L), H1975 (LT) cells Concentration: Incubation Time: 2 h Result: Inhibited EGFR with common activating mutations of HCC827 (D), HCC4011 (L) cells and T790M mutation of H1975 (LT) with IC 50 s of 4, 1.3 and 9.8 nM respectively, which more potently than WT EGFR (A431 (WT); IC 50 of 35 nM). Western Blot AnalysisCell Line: CUTO14 (ASV) cells Concentration: 0.1 nM-1 μM Incubation Time: 6 h Result: Robustly inhibited EGFR signaling, reaching 80% and 100% inhibition of phosphorylated EGFR (pEGFR) at concentrations of 100 nM and 1 μM, respectively. Western Blot AnalysisCell Line: HCC827 (D), HCC4011 (L), H1975 (LT) cells Concentration: 0.3 nM-1 μM Incubation Time: 6 h Result: Potently inhibited EGFR and downstream signaling in HCC827 (D), HCC4011 (L) and H1975 (LT) cells. Western Blot AnalysisCell Line: H1781 (HER2 Exon 20 G776>VC ), Ba/F3 (HER2 exon 20 YVMA ) cells Concentration: 0.01, 0.1 and 1 μM Incubation Time: 6 h Result: Inhibited HER2 signaling in H1781 and Ba/F3-HER2 exon 20 YVMA mutant cells at 0.1 μM with significantly decreased phosphorylations of HER2, AKT, and ERK1/2 in a dose-dependent manner.
In Vivo
Mobocertinib succinate (3, 10, 30 mg/kg; p.o.; once daily for 20 days) significantly induces tumor growth inhibition . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female Athymic Nude-Foxn1 nu mice (human NSCLC H1975 LT tumor model) . Dosage: 3, 10, 30 mg/kg Administration: Oral; once daily for 20 days. Result: Decreased the mean tumor volume by 44% and 92% when at 3 mg/kg and 10 mg/kg, respectively, relative to the tumor size of vehicle group. Induced a 76% tumor regression relative to the pretreatment tumor size at 30 mg/kg.
Form:Solid
IC50& Target:EGFR exon 20 insertion HER2 EGFR (WT)
