| Identification | Back Directory | [Name]
2-Propen-1-one, 1-[4-[8-[[3-methyl-4-[(1-methyl-1H-benzimidazol-5-yl)oxy]phenyl]amino]pyrimido[5,4-d]pyrimidin-2-yl]-1-piperazinyl]- | [CAS]
2682003-36-5 | [Synonyms]
BI-4142
2-Propen-1-one, 1-[4-[8-[[3-methyl-4-[(1-methyl-1H-benzimidazol-5-yl)oxy]phenyl]amino]pyrimido[5,4-d]pyrimidin-2-yl]-1-piperazinyl]- | [Molecular Formula]
C28H27N9O2 | [MOL File]
2682003-36-5.mol | [Molecular Weight]
521.57 |
| Chemical Properties | Back Directory | [Boiling point ]
784.9±70.0 °C(Predicted) | [density ]
1.39±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
5.24±0.10(Predicted) | [color ]
Light yellow to yellow | [InChIKey]
JKBYBPNRTMHEGS-UHFFFAOYSA-N | [SMILES]
C(N1CCN(C2=NC=C3N=CN=C(NC4=CC=C(OC5=CC=C6N(C)C=NC6=C5)C(C)=C4)C3=N2)CC1)(=O)C=C |
| Hazard Information | Back Directory | [Description]
BI-4142 is a potent, highly selective and orally active HER2 inhibitor with an IC50= 5 nM. BI-4142 showed efficacy against HER2 exon 20 insertion-driven tumors, while preserving EGFR wt signaling. | [Uses]
BI-4142 is a potent, highly selective and orally active HER2 inhibitor with an IC50 of 5 nM[1]. | [in vivo]
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]
| Compound | Dose iv/po
(mg/kg) | tmax
(h) | Cmax
(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 |
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| [IC 50]
HER2: 5 nM (IC50) | [References]
[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. DOI:10.1038/s43018-022-00412-y |
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