Molecular Weight(MW): 471.35
BX912 is a potent and specific PDK1 inhibitor with IC50 of 12 nM, 9- and 105- fold greater selectivity for PDK1 than PKA and PKC in cell-free assays, respectively. In comparison to GSK3β, selectivity for PDK1 is 600-fold.
Purity & Quality Control
Choose Selective PDK-1 Inhibitors
Click to view more
2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.
|Description||BX912 is a potent and specific PDK1 inhibitor with IC50 of 12 nM, 9- and 105- fold greater selectivity for PDK1 than PKA and PKC in cell-free assays, respectively. In comparison to GSK3β, selectivity for PDK1 is 600-fold.|
BX912 prevents ChcK1, PKA, c-kit, and KDR with IC50 of 0.83, 0.11, 0.85, and 0.41 μM, resepectively. BX912 blocks PDK1/Akt signaling in tumor cells and suppresses the anchorage-dependent growth of a variety of tumor cell lines (such as PC-3 cells ) in culture or induces apoptosis. A number of cancer cell lines (such as MDA-468 breast cancer) with elevated Akt activity are >30-fold more sensitive to growth inhibition by PDK1 inhibitor BX912 in soft agar than on tissue culture plastic, consistent with the cell survival function of the PDK1/Akt signaling pathway, which is particularly important for unattached cells. BX912 potently blocks PDK1 enzyme activity in a direct kinase assay format, although BX912 fails to block preactivated AKT2 activity (IC50 > 10 μM). Therefore, BX-912 is a direct inhibitor of PDK1. BX912 is a competitive inhibitor of PDK1 activity with respect to its substrate, ATP, suggesting that BX912 binds to the ATP binding pocket of PDK1. The aminopyrimidine backbone of BX912 adopts a similar orientation in the active site of PDK1. BX912 promotes a pronounced increase in the population of MDA-468 cells with 4 N DNA content, indicative of a block at the G2/M phase of the cell cycle. BX912 also potently inhibits the growth of HCT-116 cells in soft agar, showing a 96% inhibitory effect at a dose of 1 μM. BX912 potently inhibits the growth of PC-3 cells in soft agar, displaying IC50 of 0.32 μM. 
Kinase assays:PDK1 is assayed in a direct kinase assay and a coupled assay format measuring PDK1- and PtdIns-3,4-P2-mediated activation of AKT2. For the coupled assay, the final assay mixture (60 μL) contained: 15 mM MOPS, pH 7.2, 1 mg/mL bovine serum albumin, 18 mM β-glycerol phosphate, 0.7 mM dithiothreitol, 3 mM EGTA, 10 mM MgOAc, 7.5 μM ATP, 0.2 μCi of [γ- 33P]ATP, 7.5 μM biotinylated peptide substrate (biotin-ARRRDGGGAQPFRPRAATF), 0.5 μL of PtdIns-3,4-P2-containing phospholipid vesicles, 60 pg of purified recombinant human PDK1, and 172 ng of purified recombinant human AKT2. After incubation for 2 hours at room temperature, the biotin-labeled peptide is captured from 10 μL of the assay mixture on streptavidin-coated SPA beads, and product formation is measured by scintillation proximity in a Wallac MicroBeta counter. The product formed is proportional to the time of incubation and to the amount of PDK1 and inactive AKT2 added. PDK1 is added at suboptimal levels so that the assay could sensitively detect inhibitors of AKT2 activation as well as direct inhibitor BX912 of PDK1 or AKT2. To measure PDK1 activity directly, the final assay mixture (60 μL) contained 50 mM Tris-HCl, pH 7.5, 0.1 mM EGTA, 0.1 mM EDTA, 0.1% β-mercaptoethanol, 1 mg/mL bovine serum albumin, 10 mM MgOAc, 10 μM ATP, 0.2 μCi of [γ-33P]ATP, 7.5 μM substrate peptide (H2N-ARRRGVTTKTFCGT), and 60 ng of purified recombinant human PDK1. After 4 hours at room temperature, 25 mM EDTA is added and a portion of the reaction mixture on P81 phosphocellulose paper is spotted. The filter paper is washed three times with 0.75% phosphoric acid and once with acetone. After drying, the filter-bound labeled peptide is quantified using a phosphorimager.
|In vitro||DMSO||94 mg/mL (199.42 mM)|
|Ethanol||94 mg/mL (199.42 mM)|
|In vivo||30% PEG400+0.5% Tween80+5% propylene glycol||30 mg/mL|
* 1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).
Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
Molecular Weight Calculator
Enter the chemical formula of a compound to calculate its molar mass and elemental composition:
Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2
Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.