PDK1 (3-phosphoinositide-dependent protein kinase 1) plays an important role in growth factor signalling cascades by phosphorylating and activating a group of protein kinases belonging to the AGC [PKA (protein kinase A)/PKG (proteinkinase G)/PKC (protein kinase C)]-kinase family. GSK2334470 inhibits PDK1 with an IC₅₀ of ~10 nM. Addition of GSK2334470 to HEK (human embryonic kidney)-293, U87 or MEF (mouse embryonic fibroblast) cells ablated T-loop residue phosphorylation and activation of SGK isoforms and S6K1 induced by serum or IGF1 (insulin-like growth factor 1). GSK2334470 also inhibited T-loop phosphorylation and activation of Akt, but was more efficient at inhibiting Akt in response to stimuli such as serum that activated the PI3K (phosphoinositide 3-kinase) pathway weakly. GSK2334470 inhibited activation of an Akt1 mutant lacking the PH domain (pleckstrin homology domain) more potently than full-length Akt1, suggesting that GSK2334470 is more effective at inhibiting PDK1 substrates that are activated in the cytosol rather than at the plasma membrane. GSK2334470 also suppressed T-loop phosphorylation and activation of RSK2 (p90 ribosomal S6 kinase 2), another PDK1 target activated by the ERK (extracellular-signal-regulated kinase) pathway[2]. Furthermore, chemical inhibition of PDK1 using the specific inhibitor GSK2334470 (1 µM) resulted in total abrogation of the EGF-induced intracellular calcium increase and inositol phosphates accumulation in MDA-MB-231 cells[3].
GSK2334470 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
F-36P cells
Proliferation assay
Antiproliferative activity against human F-36P cells, IC50=0.28 μM
21341675
insect cells
Function assay
Inhibition of recombinant full length PDK1 (unknown origin) expressed in insect cells assessed as inhibition of Akt activation measured for 30 mins in presence of [gamma32P-ATP], IC50=0.01 μM
23448267
K562 cells
Proliferation assay
Antiproliferative activity against human K562 cells, IC50=18 μM
21341675
OCI-AML2 cells
Proliferation assay
Antiproliferative activity against human OCI-AML2 cells, IC50=0.35 μM
Antiproliferative activity against human F-36P cells, IC50=0.28 μM
21341675
insect cells
Function assay
Inhibition of recombinant full length PDK1 (unknown origin) expressed in insect cells assessed as inhibition of Akt activation measured for 30 mins in presence of [gamma32P-ATP], IC50=0.01 μM
23448267
K562 cells
Proliferation assay
Antiproliferative activity against human K562 cells, IC50=18 μM
21341675
OCI-AML2 cells
Proliferation assay
Antiproliferative activity against human OCI-AML2 cells, IC50=0.35 μM
21341675
OCI-AML3 cells
Proliferation assay
Antiproliferative activity against human OCI-AML3 cells, IC50=0.52 μM
21341675
PC3 cells
Function assay
Inhibition of PDK1-mediated AKT phosphorylation at Thr308 residue in human PC3 cells by ELISA, IC50=0.113 μM
21341675
PC3 cells
Function assay
Inhibition of PDK1-mediated RSK phosphorylation at Ser221 residue in human PC3 cells by ELISA, IC50=0.293 μM
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