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) signaling
- glycodelin-transfected HEC-1B human endometrial adenocarcinoma cells.
- HeLa and Hs578T cells to test its effect on formylglycinamidine ribonucleotide synthase?(FGAMS) assembly
Definition
ChEBI: (3S,6R)-1-[6-(3-amino-1H-indazol-6-yl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide is a member of indazoles.
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
