product name GSK2334470
Description: GSK2334470 is a novel PDK1 inhibitor with IC50 of ~10 nM in a cell-free assay, with no activity at other close related AGC-kinases. GSK2334470 prevents PDK1 from activating full-length Akt1or mutant Akt1 lacking the PH domain. It also inhibits phosphorylation of the PDKtide peptide substrate. GSK2334470 shows no significant inhibitory effect on 93 other protein kinases (including 13 AGC-kinases) and 15 lipid kinases. GSK2334470 markedly inhibits the IGF1-induced T-loop phosphorylation of SGK1, SGK2 and SGK3 overexpressed in HEK293 cells. GSK2334470 is also reported to suppress the activity of S6K1.
References: Biochem J. 2011 Jan 15;433(2):357-69; J Cell Sci. 2012 Jul 1;125(Pt 13):3153-63; PLoS One. 2013;8(3):e58703.
462.59
Formula
C25H34N8O
CAS No.
1227911-45-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 90 mg/mL (194.6 mM)
Water: <1 mg/mL
Ethanol: 90 mg/mL (194.6 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: GSK2334470 inhibits PDK1 from activating full-length Akt1 in the presence of PtdIns(3,4,5)P3-containing lipid vesicles or a mutant of Akt1 lacking the PH domain (ΔPH-Akt1) with IC50 of ~10 nM. GSK2334470 also similarly inhibits PDK1 from phosphorylating the PDKtide peptide substrate with IC50 of ~10 nM. GSK2334470 (0.1 μM–0.3 μM) induces significant dose-dependent inhibition of endogenous NDRG1 with over 50% reduction in phosphorylation in HEK-293 cells. GSK2334470 (30 nM) induces a significant dose-dependent inhibition of the T-loop phosphorylation of each SGK isoform in HEK-293 cells. GSK2334470 (1 μM) inhibits hydrophobic motif phosphorylation of S6K1 to a similar extent as T-loop phosphorylation in HEK-293 cells. GSK2334470 (3 μM) also suppresses S6K1 activity and phosphorylation induced by IGF1 stimulation of serum-starved HEK-293 cells. GSK2334470 (3 μM) markedly inhibits the phosphorylation of several Akt substrates [FoxO (forkhead box O), GSK3 and PRAS40]. GSK2334470 (3 μM) also induces near maximal inhibition of Akt1 activity and phosphorylation within 5 min, and Akt substrate phosphorylation (FoxO, GSK3 and PRAS40) is inhibited at a slightly later time point (10 min). GSK2334470 (0.3 μM) significantly inhibits phosphorylation of Akt or PRAS40/GSK3 in PDK1K465E/K465E knock-in but not wild-type ES cells. GSK2334470 (1 μM) effectively suppresses SGK1 activity as judged by the inhibition of NDRG1 phosphorylation in U87 glioblastoma cells. GSK2334470 (1 μM) also potently suppresses activation of S6K1 (Figure 7B) as well as SGK1 in MEF (mouse embryonic fibroblast) cells. GSK2334470 (0.1 μM) induces ~50% inhibition of RSK2 activity in HEK-293 cells. GSK2334470 (30 µM) suppresses U46619 induced Ca2+-sensitized force in α-toxin permeabilized rabbit pulmonary artery SM. GSK2334470 (30 µM) results in a significant decrease in the contractile force in response to [Ca2+]. GSK2334470 (1 μM) results in total abrogation of the EGF-induced intracellular calcium increase and inositol phosphates accumulation in MDA-MB-231 cells. GSK2334470 (1 μM) inhibits PLCγ1 Tyr783 phosphorylation in MDA-MB-231 cells. Kinase Assay: Cell Assay: |
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| In Vivo | |
| Animal model | |
| Formulation & Dosage | |
| References | Biochem J. 2011 Jan 15;433(2):357-69; J Cell Sci. 2012 Jul 1;125(Pt 13):3153-63; PLoS One. 2013;8(3):e58703. |
