PHT-427

PDPK1

409, 61

BxPC-3, Panc-1, MiaPaCa-2, PC-3, SKOV-3, A-549 or MCF-7 cells are injected subcutaneously into the flanks of female scid mice.

1-50 uM

40 to 50 mg/mL in sesame seed oil

PH-427 is a pleckstrin homology domain inhibitor to Akt/PDPK1. PH-427 significantly reduces phospho-Ser241-PDPK1 phospho-Thr308-Akt in PC-3 prostate cancer cells at 10 uM, which shows that PHT-427 could inhibit both Akt and PDKP1. PHT-427 also inhibits translocation of the Akt and PDKP1 PH domains in plasma membrane. [1] PHT-427 induces apoptosis and inhibits AKT phosphorylation with IC50 of 8.6 uM (in BxPC-3 cells), which mainly on its Ser473 residue and less strongly on Thr308 residue without affecting total Akt protein expression. PHT-427 also shows antiproliferation in Panc-1 cells with IC50 of 65 uM. [2]

Surface plasmon resonance (SPR) spectroscopy binding assays, All interaction analyses are performed with a Biacore 2000, Biacore 2000 Control Software v3.2, and BIAevaluation v4.1 analysis software. The PH domain GST-fusion proteins (Akt1, IRS1, and PDK1) are immobilized on a CM5 Sensorchip using Biacore's Amine Coupling Kit to a level of 10, 000 Response units (RUs). Small molecule analytes at concentrations ranging from 0.1 to 10, the predicted KD are injected at a high flow rate (30uL/min). DMSO concentrations in all samples and running buffer are 1% (v/v) or less.

DMSO 82 mg/mL, Water <1 mg/mL, Ethanol 60 mg/mL

4-dodecyl-N-(1, 3, 4-thiadiazol-2-yl)benzenesulfonamide