BX-320

BX-320 is a selective, ATP-competitive, orally acitive, and direct PDK1 inhibitor with an IC₅₀ of 30 nM in a direct kinase assay format. BX-320 also induces apoptosis. Anticancer effect^[1]. 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]. 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].