BI-4142 is a potent, highly selective and orally active HER2 inhibitor with an IC 50 of 5 nM
In Vitro
BI-4142 shows inhibition with IC 50 values of 10 nM, 18 nM, 270 nM and 2400 nM against HEK HER2 YVMA , Ba/F3 HER2 YVMA , HEK EGFR WT and Ba/F3 EGFR WT , respectively. BI-4142 (1 nM-5 μM, 72 h or 96 h) shows antiproliferative activity against tumor cells. BI-4142 displays good permeability and no PgP-mediated efflux liability in the CaCo-2 assay. BI-4142 inhibits HER2-dependent cell lines and inhibits downstream signaling. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: NCI-H2170 HER2 WT , NCI-H2170 HER2 YVMA , A431 EGFR WT , Ba/F3 HER2 YVMA , Ba/F3 HER2 YVMA,S783C , Ba/F3 EGFR WT and Ba/F3 EGFR C775S cells Concentration: 1 nM-5 μM Incubation Time: 72 h or 96 h Result: Showed antiproliferative effect with IC 50 values of 16 nM, 82 nM, >5 µM, 4 nM, 24 nM, 718 nM and 43 nM against NCI-H2170 HER2 WT , NCI-H2170 HER2 YVMA , A431 EGFR WT , Ba/F3 HER2 YVMA , Ba/F3 HER2 YVMA,S783C , Ba/F3 EGFR WT and Ba/F3 EGFR C775S , respectively.
In Vivo
BI-4142 (0-100 mg/kg; p.o.; twice per day for 40 days) inhibits tumor growth and inhibits oncogenic signaling . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: NMRI-Foxn1nu mice, PC-9 HER2 YVMA xenograft model Dosage: 3, 10, 30 and 100 mg/kg Administration: Oral administration, twice per day for 40 days Result: Resulted in tumor regressions in a dose-dependent manner (113%, 126%, 153% and 166% tumor growth inhibition at 3, 10, 30 and 100 mg/kg, respectively). Animal Model: BomTac:NMRI Foxn1nu mice Dosage: 1 mg/kg or 10mg/kg and 100 mg/kg Administration: IV for 1 mg/kg, PO for 10mg/kg and 100 mg/kg (Pharmacokinetic Analysis) Result: In vivo mouse PK data for BI-4142 Compound Dose iv/po (mg/kg) tmax (h) C max (nM) AUD (h•nM) Plasma CL (mL/min/kg) % F i.v., 1mg/kg n/a n/a 3,280 9.69 n/a BI-4142 p.o., 10 mg/kg 0.83 8,600 23,200 n/a 71 p.o., 100 mg/kg 0.67 36,400 196,000 n/a 60
IC50& Target:HER2 5 nM (IC 50 )
