| 生物活性 | BI-4142 is a potent, highly selective and orally activeHER2inhibitor with anIC50of 5 nM[1]. |
| IC50& Target | |
体外研究
(In Vitro) | BI-4142 shows inhibition with IC50values of 10 nM, 18 nM, 270 nM and 2400 nM against HEK HER2YVMA, Ba/F3 HER2YVMA, HEK EGFRWTand 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].
Cell Proliferation Assay[1] | Cell Line: | NCI-H2170 HER2WT, NCI-H2170 HER2YVMA, A431 EGFRWT, Ba/F3 HER2YVMA, Ba/F3 HER2YVMA,S783C, Ba/F3 EGFRWTand Ba/F3 EGFRC775Scells | | Concentration: | 1 nM-5 μM | | Incubation Time: | 72 h or 96 h | | Result: | Showed antiproliferative effect with IC50values of 16 nM, 82 nM, >5 μM, 4 nM, 24 nM, 718 nM and 43 nM against NCI-H2170 HER2WT, NCI-H2170 HER2YVMA, A431 EGFRWT, Ba/F3 HER2YVMA, Ba/F3 HER2YVMA,S783C, Ba/F3 EGFRWTand Ba/F3 EGFRC775S, respectively. |
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体内研究
(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 HER2YVMAxenograft 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
(honM) | 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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| 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(191.73 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.9173 mL | 9.5864 mL | 19.1729 mL | | 5 mM | 0.3835 mL | 1.9173 mL | 3.8346 mL | | 10 mM | 0.1917 mL | 0.9586 mL | 1.9173 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。 |
