BI-1622

• CAT Number: I043354
• CAS Number: 2681392-19-6
• Molecular Formula: C26H24N10O2
• Molecular Weight: 508.53
• Purity: ≥95%
• Synonyms: 1-[4-[4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)anilino]pyrimido[5,4-d]pyrimidin-6-yl]piperazin-1-yl]prop-2-en-1-one
• InChI: InChI=1S/C26H24N10O2/c1-3-23(37)34-8-10-35(11-9-34)26-27-14-20-24(33-26)25(30-15-28-20)32-18-4-5-21(17(2)12-18)38-19-6-7-36-22(13-19)29-16-31-36/h3-7,12-16H,1,8-11H2,2H3,(H,28,30,32)
• InChIKey: KXUBSQUYDKKQTR-UHFFFAOYSA-N
• SMILES: CC1=C(C=CC(=C1)NC2=NC=NC3=CN=C(N=C32)N4CCN(CC4)C(=O)C=C)OC5=CC6=NC=NN6C=C5

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].
BI-1622 (0-5 µM, 72 h or 96 h) inhibits the proliferation of HER2-dependent cell lines[1].
BI-1622 induces a dose-dependent decrease in pHER2 and pERK levels in NCI-H2170 HER2YVMA and PC-9 HER2YVMA cells with an accompanying decrease in DUSP6 messenger RNA levels[1].
BI-1622 displays good permeability and no PgP-mediated efflux liability[1].
BI-1622 shows good in vitro clearance in mouse liver microsomes and mouse hepatocytes[1].
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].

Reference

[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.
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