BI-1622 是一种口服有效的和高选择性HER2(ERBB2) 抑制剂，IC50为 7 nM。BI-1622对EGFR的选择性大于 25 倍。BI-1622 在转染 H2170 和 PC9 细胞的移植瘤小鼠模型中表现出较高的体内的抗肿瘤效果，具有良好的药物代谢和药代动力学特性。
| 生物活性 | BI-1622 is an orally active, potent and highly selectiveHER2(ERBB2) inhibitor, with anIC50of 7 nM. BI-1622 shows greater than 25-fold selectivity overEGFR. BI-1622 shows high antitumor efficacyin vivoin xenograft mouse tumor models with engineered H2170 and PC9 cells and had a favorable drug metabolism and pharmacokinetics profile[1]. |
| IC50& Target | HER2 7 nM (IC50) | ErbB4 | EGFR | CDK11B | JAK3 |
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体外研究
(In Vitro) | 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 goodin vitroclearance in mouse liver microsomes and mouse hepatocytes[1].
Cell Proliferation Assay[1] | Cell Line: | Ba/F3 cells | | Concentration: | 0-5 μM | | Incubation Time: | 72 h or 96 h | | Result: | Potently inhibited the proliferation of cancer cell lines dependent on amplified HER2 or an NRG-1 fusion. Inhibited different HER2 oncogenic variants and HER2WT with IC50values below 50 nM in tumor cell lines, while sparing EGFRWT-driven cells. |
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体内研究
(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 signalingin 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%. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, protect from light *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light) |
| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(196.65 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.9665 mL | 9.8323 mL | 19.6645 mL | | 5 mM | 0.3933 mL | 1.9665 mL | 3.9329 mL | | 10 mM | 0.1966 mL | 0.9832 mL | 1.9665 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (protect from light)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 |
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