[CAS NO. 1227911-45-6] GSK2334470
PRODUCTS SPECIFICATIONS [1227911-45-6]
DESCRIPTION [1227911-45-6]
Overview
| MDL | MFCD21608525 |
|---|---|
| Molecular Weight | 462.59 |
| Molecular Formula | C25H34N8O |
| SMILES | O=C([C@@H]1CN(C2=NC(NC)=NC(C3=CC4=C(C=C3)C(N)=NN4)=C2)[C@H](C)CC1)NC5CCCCC5 |
5 Publications Citing Use of MCE
Summary
GSK2334470 is a highly specific and potent inhibitor of PDK1 with an IC 50 of 10 nM.
IC50 & Target
IC50: 10 nM(PDK1) [1]
In Vitro
Small molecule GSK2334470 inhibits PDK1 with an IC 50 of ~10 nM, but does not suppress the activity of 93 other protein kinases including 13 AGC-kinases most related to PDK1 at 500-fold higher concentrations. Addition of GSK2334470 ablates T-loop residue phosphorylation and activation of SGK isoforms and S6K1 induced by serum or IGF-1 (insulin-like growth factor 1). GSK2334470 and AZD8055 effectively inhibite phosphorylation of PDK1 and mTOR, respectively, and induce higher G0–G1 ratio in LAN-1-MK than that in LAN-1 as well. PDK1 and mTOR inhibitors effecte on phosphorylation of GSK3 β in some of resistant sublines [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
The efficacy of the PDK1 inhibitor (PDKi) GSK2334470 is tested in newborn Braf V600E ::Pten −/− mice subjected to systemic administration of 4-HT. Twice weekly administration of PDK1 results in marked inhibition of pigmented lesions and concomitant melanomagenesis, as well as significant inhibition of lung metastases, seen by H&E staining-based quantification (~80%), and lymph node metastases as by S100 immunostaining, similar to the phenotype seen upon genetic ablation of Pdk1 [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 50 mg/mL ( 108.09 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.1617 mL | 10.8087 mL | 21.6174 mL |
| 5 mM | 0.4323 mL | 2.1617 mL | 4.3235 mL |
| 10 mM | 0.2162 mL | 1.0809 mL | 2.1617 mL |
References
- [1] Najafov A, et al. Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1. Biochem J.?2011 Jan 15;433(2):357-69.
- [2] Qi L, et al. PDK1-mTOR signaling pathway inhibitors reduce cell proliferation in MK2206 resistant neuroblastoma cells. Cancer Cell Int.?2015 Sep 29;15:91.
- [3] Scortegagna M, et al. Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of Braf(V600E)::Pten(-/-) melanoma. Oncogene. 2014 Aug 21;33(34):4330-9.