3-phosphoinositide dependent protein kinase 1 | PDK1 family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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3-phosphoinositide dependent protein kinase 1

Target id: 1519

Nomenclature: 3-phosphoinositide dependent protein kinase 1

Abbreviated Name: PDK1

Family: PDK1 family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: ON :     3-phosphoinositide dependent protein kinase 1 has curated data in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 556 16p13.3 PDPK1 3-phosphoinositide dependent protein kinase 1
Mouse - 559 17 A3.3 Pdpk1 3-phosphoinositide dependent protein kinase 1
Rat - 559 10q12 Pdpk1 3-phosphoinositide dependent protein kinase-1
Previous and Unofficial Names
PkB kinase | protein kinase B kinase | 3-phosphoinositide dependent protein kinase-1
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  PDK1 in complex with inhibitor MP7
Resolution:  1.75Å
Species:  Human
References:  13
Image of receptor 3D structure from RCSB PDB
PDB Id:  1H1W
Resolution:  2.0Å
Species:  Human
References:  2
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human PDK1 kinase domain in complex with UCN-01
Ligand:  7-hydroxystaurosporine
Resolution:  2.51Å
Species:  Human
References:  8
Enzyme Reaction
EC Number:

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
PHT-427 Hs Inhibition 5.3 pKi 11
pKi 5.3 (Ki 5.2x10-6 M) [11]
Description: Assay using purified recombinant pleckstrin homology domain of human PDK1
GSK2334470 Hs Inhibition 8.6 pIC50 10
pIC50 8.6 (IC50 2.51x10-9 M) [10]
OSU-03012 Hs Inhibition 8.1 pIC50 18
pIC50 8.1 (IC50 9x10-9 M) [18]
BX-795 Hs Inhibition 8.0 pIC50 4
pIC50 8.0 (IC50 1.1x10-8 M) [4]
Description: In a direct kinase activity measuring phosphorylation od a small peptide substrate mimetic
BX-912 Hs Inhibition 7.6 pIC50 4
pIC50 7.6 (IC50 2.6x10-8 M) [4]
Description: In a direct kinase activity measuring phosphorylation od a small peptide substrate mimetic
7-hydroxystaurosporine Hs Inhibition 7.5 pIC50 14
pIC50 7.5 (IC50 3.3x10-8 M) [14]
compound 1 [PMID: 20005102] Hs Inhibition 7.3 pIC50 9
pIC50 7.3 (IC50 5x10-8 M) [9]
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 3,17

Key to terms and symbols Click column headers to sort
Target used in screen: PDPK1
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 8.8 pKd
lestaurtinib Hs Inhibitor Inhibition 8.5 pKd
tamatinib Hs Inhibitor Inhibition 6.9 pKd
midostaurin Hs Inhibitor Inhibition 6.7 pKd
KW-2449 Hs Inhibitor Inhibition 6.2 pKd
ruboxistaurin Hs Inhibitor Inhibition 6.2 pKd
SU-14813 Hs Inhibitor Inhibition 5.6 pKd
SB203580 Hs Inhibitor Inhibition <5.5 pKd
erlotinib Hs Inhibitor Inhibition <5.5 pKd
GSK690693 Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.


Reference: 1,5

Key to terms and symbols Click column headers to sort
Target used in screen: PDK1/PDK1(PDPK1)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Hs Inhibitor Inhibition 1.6 -1.0 0.0
staurosporine Hs Inhibitor Inhibition 4.4 0.5 0.0
SB 218078 Hs Inhibitor Inhibition 10.6 27.0 4.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 19.3 3.0 0.0
midostaurin Hs Inhibitor Inhibition 21.8 2.0 1.0
JAK inhibitor I Hs Inhibitor Inhibition 27.0 3.0 1.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 46.9 6.0 2.0
Gö 6976 Hs Inhibitor Inhibition 63.2 6.0 6.0
Cdk4 inhibitor Hs Inhibitor Inhibition 66.1 75.0 29.0
Cdk2 inhibitor IV Hs Inhibitor Inhibition 69.1 20.0 3.0
Displaying the top 10 most potent ligands  View all ligands in screen »
General Comments
PDK1 phosphorylates and activates the AGC kinase members which are regulated by phosphatidylinositol 3-kinase (PI 3-kinase), including AKT, PKC, S6K and SGK [12]. The PDK1/AKT signaling pathway plays a key role in cancer cell growth, survival, and tumour angiogenesis and represents a promising target for oncology therapeutics [6,15].


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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1039-45. [PMID:22037377]

2. Biondi RM, Komander D, Thomas CC, Lizcano JM, Deak M, Alessi DR, van Aalten DM. (2002) High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory phosphopeptide docking site. EMBO J., 21 (16): 4219-28. [PMID:12169624]

3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]

4. Feldman RI, Wu JM, Polokoff MA, Kochanny MJ, Dinter H, Zhu D, Biroc SL, Alicke B, Bryant J, Yuan S et al.. (2005) Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J. Biol. Chem., 280 (20): 19867-74. [PMID:15772071]

5. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J., 451 (2): 313-28. [PMID:23398362]

6. Hanada M, Feng J, Hemmings BA. (2004) Structure, regulation and function of PKB/AKT--a major therapeutic target. Biochim. Biophys. Acta, 1697 (1-2): 3-16. [PMID:15023346]

7. Kawano Y, Nakae J, Watanabe N, Fujisaka S, Iskandar K, Sekioka R, Hayashi Y, Tobe K, Kasuga M, Noda T et al.. (2012) Loss of Pdk1-Foxo1 signaling in myeloid cells predisposes to adipose tissue inflammation and insulin resistance. Diabetes, 61 (8): 1935-48. [PMID:22586579]

8. Komander D, Kular GS, Bain J, Elliott M, Alessi DR, Van Aalten DM. (2003) Structural basis for UCN-01 (7-hydroxystaurosporine) specificity and PDK1 (3-phosphoinositide-dependent protein kinase-1) inhibition. Biochem. J., 375 (Pt 2): 255-62. [PMID:12892559]

9. Lin H, Yamashita DS, Zeng J, Xie R, Verma S, Luengo JI, Rhodes N, Zhang S, Robell KA, Choudhry AE et al.. (2010) 2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles. Bioorg. Med. Chem. Lett., 20 (2): 679-83. [PMID:20005102]

10. Medina JR, Becker CJ, Blackledge CW, Duquenne C, Feng Y, Grant SW, Heerding D, Li WH, Miller WH, Romeril SP et al.. (2011) Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors. J. Med. Chem., 54 (6): 1871-95. [PMID:21341675]

11. Meuillet EJ, Zuohe S, Lemos R, Ihle N, Kingston J, Watkins R, Moses SA, Zhang S, Du-Cuny L, Herbst R et al.. (2010) Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor. Mol. Cancer Ther., 9 (3): 706-17. [PMID:20197390]

12. Mora A, Komander D, van Aalten DM, Alessi DR. (2004) PDK1, the master regulator of AGC kinase signal transduction. Semin. Cell Dev. Biol., 15 (2): 161-70. [PMID:15209375]

13. Nagashima K, Shumway SD, Sathyanarayanan S, Chen AH, Dolinski B, Xu Y, Keilhack H, Nguyen T, Wiznerowicz M, Li L et al.. (2011) Genetic and pharmacological inhibition of PDK1 in cancer cells: characterization of a selective allosteric kinase inhibitor. J. Biol. Chem., 286 (8): 6433-48. [PMID:21118801]

14. Sato S, Fujita N, Tsuruo T. (2002) Interference with PDK1-Akt survival signaling pathway by UCN-01 (7-hydroxystaurosporine). Oncogene, 21 (11): 1727-38. [PMID:11896604]

15. Shiojima I, Walsh K. (2002) Role of Akt signaling in vascular homeostasis and angiogenesis. Circ. Res., 90 (12): 1243-50. [PMID:12089061]

16. Sturm EM, Parzmair GP, Radnai B, Frei RB, Sturm GJ, Hammer A, Schuligoi R, Lippe IT, Heinemann A. (2015) Phosphoinositide-dependent protein kinase 1 (PDK1) mediates potent inhibitory effects on eosinophils. Eur. J. Immunol., 45 (5): 1548-59. [PMID:25645675]

17. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol., 17 (11): 1241-9. [PMID:21095574]

18. Zhu J, Huang JW, Tseng PH, Yang YT, Fowble J, Shiau CW, Shaw YJ, Kulp SK, Chen CS. (2004) From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. Cancer Res., 64 (12): 4309-18. [PMID:15205346]

How to cite this page

PDK1 family: 3-phosphoinositide dependent protein kinase 1. Last modified on 15/02/2017. Accessed on 20/01/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1519.