Biological Activity
BX-912 is a potent PDK1 inhibitors with an IC50 of 12 nM.
In Vitro
BX-912 also inhibits PKA, KDR, CDK2/cyclin E, Chck1, c-Kit, PKC, T-Fyn, Insulin receptor, and GSK3β with IC50s of 110 nM, 410 nM, 650 nM, 830 nM, 850 nM, 1.25 μM, 2.1 μM, 6.1 μM and 7.4 μM in kinase assays, respectively. BX-912 is identified in a coupled assay measuring PDK1- and PtdIns-3,4-P2-mediated Akt activation, which can detect inhibitors of PDK1, AKT2, or other steps critical for activation of AKT2. BX-912 potently inhibits PDK1 enzyme activity in a direct kinase assay format (IC50=26), although BX-912 fails to block preactivated AKT2 activity (IC50>10 μM). BX-912 binds to the ATP binding site of PDK1. The aminopyrimidine backbone of BX-912 adopts a similar orientation in the active site of PDK1. To examine the kinase selectivity of BX-912, its effects on the in vitro activity of 10 different Ser/Thr and tyrosine kinases are determined, including the related AGC kinases PKA and PKCα. BX-912 is 9-fold selective for PDK1 relative to PKA. BX-912 blocks PDK1 activity in PTEN-negative PC-3 cells. PTEN-negative PC-3 cells display constitutive activation of Akt which is reflected in high levels of the PDK1 product, phospho-Thr308-Akt[1].
In Vivo
No in vivo data are provided in the current product source. Contact us for further information.
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
