| 体外研究: |
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. 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. 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. BX-320 (0.3-10 μM; for 18 hours) greatly reduces the amount of both p-Thr308-Akt and p-Thr386-S6K1. |