GSK2334470

Reagent Authentication Certificate:

Chemical Probes Portal GSK2334470.pdf

Protein target name:

PDK1

Mechanism of action:

Type I Inhibitor

Recommended Concentration for use in cells:

30 nM - 1 uM

Probe Availability

MedChem Express (1227911-45-6)

Tocris (GSK 2334470)

Abcam (1227911-45-6)

MilliporeSigma (1227911-45-6)

Cayman (1227911-45-6)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

AGC

HUGO ID:

HGNC:8816

Entrez gene ID:

5170

UNIPROT ID:

O15530

Probe Details

Chemical Probes Portal ID:

CPP79

Probe alias:

GSK-470, GSK 2334470, GSK-2334470

PubChem CID:

46215815

ChEMBL ID:

CHEMBL1765740

SMILES string:

C[C@@H]1CC[C@@H](CN1C2=NC(=NC(=C2)C3=CC4=C(C=C3)C(=NN4)N)NC)C(=O)NC5CCCCC5

InChi Key:

QLPHOXTXAKOFMU-WBVHZDCISA-N

PAINs evaluation:

PAINs free

Physico-chemical properties

NMR:

1H NMR (400 MHz, CD3OD): δ 1.16-1.32 (m, 3H), 1.29 (d, J = 6.8 Hz, 3H), 1.34-1.45 (m, 2H), 1.65-1.68 (m, 1H), 1.76-1.81 (m, 5H), 1.85-1.92 (m, 2H), 1.97-2.05 (m, 1H), 2.35-2.42 (m, 1H), 2.97 (s, 3H), 3.11-3.15 (m, 1H), 3.64-3.70 (m, 1H), 4.45-4.65 (bs, 1H), 4.72-4.92 (bs, 1H), 6.45 (s, 1H), 7.52 (dd, J = 8.5, 1.1 Hz, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.85 (s, 1H). 13C NMR (101 MHz, DMSO-d6): δ 14.6, 22.9, 24.6, 25.3, 27.9, 29.0, 32.5, 42.6, 47.2, 89.1, 107.7, 114.7, 116.6, 119.9, 136.7, 141.7, 149.2, 162.5, 163.0, 163.3, 172.3

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

2.5 nM

Off target activity

Potency assay (off target):

GSK2334470 was tested against a panel of 285 kinases and found to be >1,000-fold selective for PDK1, inhibiting only 24 kinases >50% at 10 uM.

In cell validation

On target activity in cells

Potency in cells:

IC50

113 nM

Potency assay (cells):

Inhibition of phosphorylation of a protein substrate in PC3 cells

Target engagement assay (cells):

Indirect: inhibition of protein substrate phosphorylation

In vivo validation

Organism:

SCID mice

Dose:

100 mg/kg

Route of delivery:

Intraperitoneal

Cmax:

4510 mg/mL

Organ of Interest

Organ (O):

xenograft

Target engagement assay:

Indirect: inhibition of protein substrate phosphorylation in xenograft tissue

Primary Reference

Reference (doi):

10.1021/jm101527u

Reference (PMID):

21341675

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

This compound is a potent and selective inhibitor of 3-phosphoinositide-dependent protein kinase 1 (PDK1). It has low nanomolar potency against the PDK1 enzyme. GSK2334470 appears selective based on the published data. It has been tested against 95 different protein kinases, and none of them were inhibited to a significant extent at a 1 uM screening concentration. In addition, GSK2334470 does not inhibit the 15 lipid kinases that were tested. In cells, GSK2334470 is active at concentrations between 30 nM and 1 uM, depending on the particular conditions and readout being measured. The authors demonstrate, for example, inhibition of the phosphorylation of SGK1, SGK2, SGK3, P70S6K, and AKT in cells in certain contexts. No pharmacokinetic data was reported, so suitability for in vivo experiments is unknown.

Jun 20 2017 - 11:28am

GSK2334470

Probe Availability

Probe Information

Target Details

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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GSK2334470

Probe Availability

Probe Information

Target Details

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?