BI-4142 is a potent, highly selective and orally active HER2 inhibitor with an IC50 of 5 nM[1].
BI-4142 shows inhibition with IC50 values of 10 nM, 18 nM, 270 nM and 2400 nM against HEK HER2YVMA, Ba/F3 HER2YVMA, HEK EGFRWT and Ba/F3 EGFRWT, respectively[1].
BI-4142 (1 nM-5 μM, 72 h or 96 h) shows antiproliferative activity against tumor cells[1].
BI-4142 displays good permeability and no PgP-mediated efflux liability in the CaCo-2 assay[1].
BI-4142 inhibits HER2-dependent cell lines and inhibits downstream signaling[1].
Cell Proliferation Assay[1]
| Cell Line: | NCI-H2170 HER2WT, NCI-H2170 HER2YVMA, A431 EGFRWT, Ba/F3 HER2YVMA, Ba/F3 HER2YVMA,S783C, Ba/F3 EGFRWT and Ba/F3 EGFRC775S cells |
| Concentration: | 1 nM-5 μM |
| Incubation Time: | 72 h or 96 h |
| Result: | Showed antiproliferative effect with IC50 values of 16 nM, 82 nM, >5 µM, 4 nM, 24 nM, 718 nM and 43 nM against NCI-H2170 HER2WT, NCI-H2170 HER2YVMA, A431 EGFRWT, Ba/F3 HER2YVMA, Ba/F3 HER2YVMA,S783C, Ba/F3 EGFRWT and Ba/F3 EGFRC775S, respectively. |
BI-4142 (0-100 mg/kg; p.o.; twice per day for 40 days) inhibits tumor growth and inhibits oncogenic signaling[1].
| Animal Model: | NMRI-Foxn1nu mice, PC-9 HER2YVMA xenograft model[1] |
| 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[1] | ||||||||||||||||||||||||||||
| 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[1]
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[1]. Wilding B, et al. Discovery of potent and selective HER2 inhibitors with efficacy against HER2 exon 20 insertion-driven tumors, which preserve wild-type EGFR signaling. Nat Cancer. 2022 Jul;3(7):821-836.