| Identification | Back Directory | [Name]
BI-1622 | [CAS]
2681392-19-6 | [Synonyms]
BI-1622
2-Propen-1-one, 1-[4-[8-[[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]amino]pyrimido[5,4-d]pyrimidin-2-yl]-1-piperazinyl]- | [Molecular Formula]
C26H24N10O2 | [MOL File]
2681392-19-6.mol | [Molecular Weight]
508.53 |
| Hazard Information | Back Directory | [Uses]
BI-1622 is an orally active, potent and highly selective HER2 (ERBB2) inhibitor, with an IC50 of 7 nM. BI-1622 shows greater than 25-fold selectivity over EGFR. BI-1622 shows high antitumor efficacy in vivo in xenograft mouse tumor models with engineered H2170 and PC9 cells and had a favorable agent metabolism and pharmacokinetics profile[1]. | [in vivo]
BI-1622 (1 mg/kg, IV; 10 and 100 mg/kg, Orally; once) shows moderate clearance, a moderate volume of distribution, and good to moderate bioavailability[1].
BI-1622 (0-100?mg/kg, orally, twice daily) inhibits tumor growth and inhibits oncogenic signaling in vivo[1].
| Animal Model: | Female NMRI-Foxn1nu mice (6-8 weeks old, 8-10 mice per cage, engrafted subcutaneously with PC-9 HER2YVMA, NCI-H2170 HER2YVMA or NCI-N87 cells)[1] | | Dosage: | 10, 30 and 100?mg/kg | | Administration: | orally, twice daily | | Result: | In the NCI-H2170 HER2YVMA mechanistic model, 100?mg/kg twice daily BI-1622 resulted in a delay in tumor growth (73% TGI). In the ST3107 HER2 exon 20 mutant model, both BI-4142 (100?mg/kg twice daily) resulted in tumor regressions. |
| Animal Model: | NMRI Foxn1nu mice (n=3 per group)[1] | | Dosage: | 1 mg/kg (IV); 10 and 100 mg/kg (Orally) | | Administration: | IV, Orally; once (Pharmacokinetic Analysis) | | Result: | Showed moderate in vivo clearance (50% hepatic blood flow), a moderate volume of distribution, and good to moderate bioavailability of up to 68%. |
| [IC 50]
HER2: 7 nM (IC50); ErbB4; EGFR; CDK11B; JAK3 | [References]
[1] Lamarre L, 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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