1227911-45-6 Usage
Description
GSK2334470 (1227911-45-6)?is a potent (IC50?= 10 nM) and selective inhibitor of 3-Phosphoinositide-dependent kinase 1 (PDK1), which phosphorylates and activates a group of protein kinases in the AGC/PKG/PKC family.1?It is more effective at inhibiting PDK1 substrates that are activated in the cytosol rather than at the plasma membrane.1?GSK2334470 delayed melanogenesis and metastasis in Braf(V600E)::Pten(-/-)?mice.2?It also displays antitumor activity against multiple myeloma synergistically with mTORC1/2 inhibitor PP2423?and proteasome inhibitor MG-1324.
Uses
GSK2334470 has been used as an inhibitor of 3-phosphoinositide dependent protein kinase-1 (PDK-1) in: Treg cells, to identify regulators of interleukin 2 (IL-2)– signal transducer and activator of transcription 5 (STAT5) signalingglycodelin-transfected HEC-1B human endometrial adenocarcinoma cells. HeLa and Hs578T cells to test its effect on formylglycinamidine ribonucleotide synthase?(FGAMS) assembly
Biochem/physiol Actions
GSK2334470 (GSK-470) mediates cell cycle arrest. It also inhibits cellular proliferation and induces apoptosis in cancer cells.
References
1) Najafov?et al.?(2011), Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1; Biochem.J.?433?37
2) Scortegagna?et al.?(2014), Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of Braf (V600E)::Pten(-/-) melanoma; Oncogene?33?4330
3) Yang?et al.?(2017),PDK1 inhibitor GSK2334470 exerts antitumor activity in multiple myeloma and forms a novel multitargeted combination with dual mTORC1/C2 inhibitor PP242; Oncotarget?8?39185
4) Zhang?et al.?(2018), PDK1 inhibitor GSK2334470 synergizes with proteasome inhibitor MG-132 in multiple myeloma cells by inhibiting full AKT activity and increasing nuclear accumulation of PTEN protein; Oncol.Rep.?39 2951
Check Digit Verification of cas no
The CAS Registry Mumber 1227911-45-6 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,2,7,9,1 and 1 respectively; the second part has 2 digits, 4 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 1227911-45:
(9*1)+(8*2)+(7*2)+(6*7)+(5*9)+(4*1)+(3*1)+(2*4)+(1*5)=146
146 % 10 = 6
So 1227911-45-6 is a valid CAS Registry Number.
1227911-45-6Relevant articles and documents
Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors
Medina, Jesús R.,Becker, Christopher J.,Blackledge, Charles W.,Duquenne, Celine,Feng, Yanhong,Grant, Seth W.,Heerding, Dirk,Li, William H.,Miller, William H.,Romeril, Stuart P.,Scherzer, Daryl,Shu, Arthur,Bobko, Mark A.,Chadderton, Antony R.,Dumble, Melissa,Gardiner, Christine M.,Gilbert, Seth,Liu, Qi,Rabindran, Sridhar K.,Sudakin, Valery,Xiang, Hong,Brady, Pat G.,Campobasso, Nino,Ward, Paris,Axten, Jeffrey M.
, p. 1871 - 1895 (2011/05/30)
Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.
