BI-4142

• CAT Number: I043353
• CAS Number: 2682003-36-5
• Molecular Formula: C28H27N9O2
• Molecular Weight: 521.57
• Purity: ≥95%
• Synonyms: 1-[4-[4-[3-methyl-4-(1-methylbenzimidazol-5-yl)oxyanilino]pyrimido[5,4-d]pyrimidin-6-yl]piperazin-1-yl]prop-2-en-1-one
• InChI: InChI=1S/C28H27N9O2/c1-4-25(38)36-9-11-37(12-10-36)28-29-15-22-26(34-28)27(31-16-30-22)33-19-5-8-24(18(2)13-19)39-20-6-7-23-21(14-20)32-17-35(23)3/h4-8,13-17H,1,9-12H2,2-3H3,(H,30,31,33)
• InChIKey: JKBYBPNRTMHEGS-UHFFFAOYSA-N
• SMILES: CC1=C(C=CC(=C1)NC2=NC=NC3=CN=C(N=C32)N4CCN(CC4)C(=O)C=C)OC5=CC6=C(C=C5)N(C=N6)C

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].
BI-4142 (0-100 mg/kg; p.o.; twice per day for 40 days) inhibits tumor growth and inhibits oncogenic signaling[1].

Reference

[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.
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