BX-320 是一种选择性的、ATP 竞争性的、口服有效的直接PDK1抑制剂，IC50为 30 nM。BX-320 还诱导细胞凋亡 (apoptosis)。具有抗癌作用。
| 生物活性 | BX-320 is a selective, ATP-competitive, orally acitive, and directPDK1inhibitor with anIC50of 30 nM in a direct kinase assay format. BX-320 also inducesapoptosis. Anticancer effect[1]. |
体外研究
(In Vitro) | BX-320 binds to the ATP binding site of PDK1. BX-320 also inhibits Chck1, c-Kit, KDR, PKA, CDK2b/cyclin E, GSK3β, PKC with IC50s of 0.82, 0.89, 1.4, 1.4, 1.5, 4.0, and 5.7 μM, respectively[1].
BX-320 blocks PDK1/Akt signaling in tumor cells and inhibits the anchorage-dependent growth of a variety of tumor cell lines in culture or induces apoptosis[1].
BX-320 inhibits the growth of MDA-468 breast cancer cells (IC50=0.6 μM) and induces apoptosis. BX-320 promotes a 12-fold induction of caspase-3/7 activity after 48 h of treatment (IC50=0.5 μm), indicating a strong proapoptotic response[1].
BX-320 (0.3-10 μM; for 18 hours) greatly reduces the amount of both p-Thr308-Akt and p-Thr386-S6K1[1].
Cell Proliferation Assay[1] | Cell Line: | MDA-468 breast cancer cells | | Concentration: | 31.6 nM, 100 nM, 316.22 nM, 1 μM, 3.162 μM, 10 μM, and 31.6 μM | | Incubation Time: | 72 hours | | Result: | Blocked the growth of MDA-468 cells (IC50=0.6 μM), which are PTEN-negative breast tumor cells expressing high levels of activated Akt. |
Western Blot Analysis[1] | Cell Line: | PC-3 cells | | Concentration: | 0, 0.3, 1, 3, 10 μM | | Incubation Time: | 18 hours | | Result: | Reduced the amount of both phospho-Thr308-Akt and phospho-Thr386-S6K1. |
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体内研究
(In Vivo) | BX-320 (oral dosing with 200 mg/kg, twice a day for 21 days) shows efficacy in a blood-borne metastasis model. BX-320 inhibits the growth of LOX melanoma tumors in the lungs of nude mice after injection of tumor cells into the tail vein. BX-320 has efficacy in an in vivo tumor model, which may reflect an inhibition of productive implantation of tumor cells in the lung or an inhibition of subsequent tumor growth[1].
| Animal Model: | Athymic (nu/nu) female mice, 6-8 weeks old[1] | | Dosage: | 200 mg/kg; dose volume was 10 mL/kg | | Administration: | Oral gavage twice daily (12 h apart) | | Result: | Significantly inhibited the growth of lung tumors in this model. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
| 溶解性数据 | In Vivo: 1. BX-320 is dissolved in 20% (w/v) hydroxypropyl-β-cyclodextrin (20 mg/mL) adjusted to pH 4[1].
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