BMS-906024 是一种口服有效，选择性的 γ 分泌酶 (γ-secretase; gamma secretase) 抑制剂。BMS-906024 是有效的，泛Notch受体抑制剂，对 Notch1，-2，-3 和 -4 受体的IC50值分别为 1.6 nM，0.7 nM，3.4 nM 和 2.9 nM。BMS-906024 表现广谱抗肿瘤活性。
| 生物活性 | BMS-906024 is an orally active and selectiveγ-secretase(gamma secretase)inhibitor. BMS-906024 is a potent pan-Notchreceptors inhibitor withIC50s of 1.6 nM, 0.7 nM, 3.4 nM, and 2.9 nM for Notch1, -2, -3, and -4 receptors, respectively. BMS-906024 demonstrates broad-spectrum antineoplastic activity[1][2]. |
| IC50& Target | IC50: 1.6 nM (Notch1), 0.7 nM (Notch2), 3.4 nM (Notch3) and 2.9 nM (Notch4)[2] |
体外研究
(In Vitro) | BMS-906024 (5-100 nM; 72 hours) reduces Notch1 ICD levels in all six lung cancer cell lines. BMS-906024 at 100 nM, has no effect on total Notch1, and down-regulated Hes1 transcript[1].
In cancer cell proliferation assays, BMS-906024 inhibits both leukemia (TALL-1) and triple-negative breast cancer (MDA-MB-468) cells with IC50of ~4 nM[2].
BMS-906024 (100 nM; for 72 hours) enhances the anti-tumor activity of Paclitaxel in vitro[1].
Western Blot Analysis[1] | Cell Line: | NSCLC cell lines (A549, H358, H1975, H2444, H1792, HCC44) | | Concentration: | 5, 10, 25, 50, 100 nM | | Incubation Time: | 72 hours | | Result: | Reduced Notch1 ICD levels in all six lung cancer cell lines tested at concentrations as low as 5 nM, with maximal depletion at 50-100 nM. |
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体内研究
(In Vivo) | BMS-906024 (8.5 mg/kg; oral gavage; days 1 through 4 of each week for 3 weeks) significantly enhances the tumor growth inhibition of Paclitaxel (36 mg/kg). BMS-906024 enhances Paclitaxel-mediated cytotoxicity in vivo in NSCLC through a combination of inhibiting proliferation and promoting apoptosis, in a p21 and p57-independent manner[1].
BMS-906024 has a T1/2of 4.6/5.3 hours, a Cmaxof 1/0.3 μM and an AUC of 3.4/1.9 μMohour for IV/PO[2].
| Animal Model: | Six to 12-week-old female NOD scid gamma (NSG) mice with KRAS- and BRAF-WT PDX-T42 xenografts[1] | | Dosage: | 8.5 mg/kg | | Administration: | oral gavage; days 1 through 4 of each week for 3 weeks | | Result: | Significantly enhanced the tumor growth inhibition of Paclitaxel (36 mg/kg), but had no significant effect on Cisplatin (2 mg/kg) treatment. |
| Animal Model: | Mouse[2] | | Dosage: | 1 mg/kg (Pharmacokinetic Analysis) | | Administration: | IV or PO | | Result: | Had a T1/2of 4.6/5.3 hours, a Cmaxof 1/0.3 μM and an AUC of 3.4/1.9 μMohour for IV/PO. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 9.5 mg/mL(17.07 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 1.7969 mL | 8.9847 mL | 17.9695 mL | | 5 mM | 0.3594 mL | 1.7969 mL | 3.5939 mL | | 10 mM | 0.1797 mL | 0.8985 mL | 1.7969 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。-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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