PHT-427

Uses

PHT-427 is a dual Akt and PDPK1 inhibitor with Ki of 2.7 μM and 5.2 μM, respectively.

Uses

PHT-427 is a pleckstrin homology domain inhibitor to Akt and PKB Kinase (PDPK1). It can also be used for therapeutic use and biological study of mathematical modeling and parametric analysis of nanoparticle encapsulation and controlled release of a hydrophobic kinase inhibitor PHT-427.

Biological Activity

pht-427 is an inhibitor of akt and pdpk1 (ki =2.7 μm and 5.2 μm, respectively).akt is a serine/threonine-specific protein kinase that plays a vital role in multiple cellular processes including glucose metabolism, apoptosis, cell proliferation, transcription and cell migration etc.in bxpc-3 cells, pht-427 showed inhibition upon akt function with ic50 value of 8.6±0.8 μm and for its downstream substrates. pht-427 reduced the akt phosphorylation on ser473 residue and did not decrease total akt protein level. pht-427 also inhibited p70s6k and gsk3β in a dose-dependent manner. [1][2]in scid (severe combined immunodeficiency) mice of bxpc-3 pancreatic cancer xenografts, administration of pht-427 exerted prominent antitumor activity that halted tumor growth. pht-427 in combination with erlotinib exhibited greater than additive antitumor activity in nsc lung cancer and with paclitaxel in breast cancer. [1][2]

in vivo

Enzyme inhibitor

This orally bioavailable, dual Akt/PDPK1 inhibitor (F.Wt. = 409.61; CAS 1191951-57-1 and 1178893-77-0; Solubility (25°C): 80 mg/mL DMSO, <1 mg/mL Water), known systematically as 4-dodecyl-N-(1,3,4-thiadiazol-2- yl)benzenesulfonamide, targets Akt (also known as Protein Kinase B, or PKB) and 3-phosphoinositide-dependent protein kinase-1, with Ki of 2.7 μM and 5.2 μM, respectively. PHT-427 was designed to bind to the pleckstrin homology (PH) auto-inhibitory domains of the signal cascade protein kinase Akt.

IC 50

PDPK1: 5.2 μM (Ki)

storage

-20°C

References

1. meuillet ej, zuohe s, lemos r et al. molecular pharmacology and antitumor activity of pht-427, a novel akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor. mol cancer ther. 2010 mar;9(3):706-17.2. moses sa, ali ma, zuohe s et al. in vitro and in vivo activity of novel small-molecule inhibitors targeting the pleckstrin homology domain of protein kinase b/akt. cancer res. 2009 jun 15;69(12):5073-81.