GSK 2334470

GSK 2334470 Property

Density 

1.30±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: ≥10mg/mL

form 

powder

pka

12.84±0.40(Predicted)

color 

white to light brown

Stability:

Stable for 1 year as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.

InChIKey

QLPHOXTXAKOFMU-WBVHZDCISA-N

SMILES

N1(C2C=C(C3=CC4=C(C=C3)C(N)=NN4)N=C(NC)N=2)[C@H](C)CC[C@H](C(NC2CCCCC2)=O)C1

Safety

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

GSK 2334470 Chemical Properties,Usage,Production

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.

storage

Store at +4°C

References

[1] AYAZ NAJAFOV. Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1.[J]. Biochemical Journal, 2011, 433 2: 357-369. DOI:10.1042/bj20101732
[2] M SCORTEGAGNA. Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of BrafV600E::Pten–/– melanoma[J]. Oncogene, 2013, 33 34: 4330-4339. DOI:10.1038/onc.2013.383
[3] CHUNMEI YANG. PDK1 inhibitor GSK2334470 exerts antitumor activity in multiple myeloma and forms a novel multitargeted combination with dual mTORC1/C2 inhibitor PP242.[J]. Oncotarget, 2017: 39185-39197. DOI:10.18632/oncotarget.16642
[4] JIN ZHANG. PDK1 inhibitor GSK2334470 synergizes with proteasome inhibitor MG‑132 in multiple myeloma cells by inhibiting full AKT activity and increasing nuclear accumulation of the PTEN protein.[J]. Oncology reports, 2018, 39 6: 2951-2959. DOI:10.3892/or.2018.6369