Pim-2 proto-oncogene, serine/threonine kinase | PIM family | IUPHAR/BPS Guide to PHARMACOLOGY

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Pim-2 proto-oncogene, serine/threonine kinase

Target id: 2159

Nomenclature: Pim-2 proto-oncogene, serine/threonine kinase

Abbreviated Name: Pim2

Family: PIM 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: OFF :     Currently no data for Pim-2 proto-oncogene, serine/threonine kinase in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 311 Xp11.23 PIM2 Pim-2 proto-oncogene, serine/threonine kinase
Mouse - 370 X A1.1 Pim2 proviral integration site 2
Rat - 311 Xq13 Pim2 Pim-2 proto-oncogene, serine/threonine kinase
Previous and Unofficial Names
pim-2 oncogene | Pim-2 proto-oncogene
Database Links
BRENDA
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  CRYSTAL STRUCTURE OF THE HUMAN PIM2 IN COMPLEX WITH A RUTHENIUM ORGANOMETALLIC LIGAND RU1
PDB Id:  2IWI
Resolution:  2.8Å
Species:  Human
References:  2
Enzyme Reaction
EC Number: 2.7.11.1

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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
LGB321 Hs Inhibition 11.7 pKi 9
pKi 11.7 (Ki 2.1x10-12 M) [9]
Description: Assayed at 4μM ATP
PIM447 Hs Inhibition 10.7 pKi 4
pKi 10.7 (Ki 1.8x10-11 M) [4]
AZD1208 Hs Inhibition 9.8 pKi 3
pKi 9.8 (Ki 1.6x10-10 M) [3]
compound 14k [PMID: 21982499] Hs Inhibition 8.2 pIC50 11
pIC50 8.2 (IC50 6x10-9 M) [11]
CX-6258 Hs Inhibition 7.6 pIC50 10
pIC50 7.6 (IC50 2.5x10-8 M) [10]
SGI-1776 Hs Inhibition 6.4 pIC50 6
pIC50 6.4 (IC50 3.63x10-7 M) [6]
ruboxistaurin Hs Inhibition <4.7 pIC50 7
pIC50 <4.7 (IC50 >2x10-5 M) [7]
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 5,12

Key to terms and symbols Click column headers to sort
Target used in screen: PIM2
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 8.7 pKd
A-674563 Hs Inhibitor Inhibition 6.7 pKd
PP-242 Hs Inhibitor Inhibition 6.6 pKd
lestaurtinib Hs Inhibitor Inhibition 6.6 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.2 pKd
GSK690693 Hs Inhibitor Inhibition 6.2 pKd
alvocidib Hs Inhibitor Inhibition 6.1 pKd
enzastaurin Hs Inhibitor Inhibition 6.1 pKd
ruboxistaurin Hs Inhibitor Inhibition 5.8 pKd
SB203580 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.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: 1,8

Key to terms and symbols Click column headers to sort
Target used in screen: Pim-2/PIM2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
SB 218078 Hs Inhibitor Inhibition 1.9 6.0 -2.0
staurosporine Hs Inhibitor Inhibition 10.4 7.0 0.0
isogranulatimide Hs Inhibitor Inhibition 34.4 5.0 0.0
STO609 Hs Inhibitor Inhibition 41.7 14.0 0.0
Cdk4 inhibitor Hs Inhibitor Inhibition 44.6 27.0 6.0
PKR inhibitor, negative control Hs Inhibitor Inhibition 48.6 17.0 3.0
casein kinase II inhibitor III Hs Inhibitor Inhibition 52.8 28.0 1.0
wortmannin Hs Inhibitor Inhibition 60.6
GF109203X Hs Inhibitor Inhibition 64.1 15.0 4.0
K-252a Hs Inhibitor Inhibition 65.0 2.0 -2.0
Displaying the top 10 most potent ligands  View all ligands in screen »

References

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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. Bullock AN, Russo S, Amos A, Pagano N, Bregman H, Debreczeni JE, Lee WH, von Delft F, Meggers E, Knapp S. (2009) Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor. PLoS ONE, 4 (10): e7112. [PMID:19841674]

3. Burger MT, Han W, Lan J, Nishiguchi G, Bellamacina C, Lindval M, Atallah G, Ding Y, Mathur M, McBride C et al.. (2013) Structure Guided Optimization, in Vitro Activity, and in Vivo Activity of Pan-PIM Kinase Inhibitors. ACS Med Chem Lett, 4 (12): 1193-7. [PMID:24900629]

4. Burger MT, Nishiguchi G, Han W, Lan J, Simmons R, Atallah G, Ding Y, Tamez V, Zhang Y, Mathur M et al.. (2015) Identification of N-(4-((1R,3S,5S)-3-Amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a Potent and Selective Proviral Insertion Site of Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase Inhibitor in Clinical Trials for Hematological Malignancies. J. Med. Chem., 58 (21): 8373-86. [PMID:26505898]

5. 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]

6. Drygin D, Haddach M, Pierre F, Ryckman DM. (2012) Potential use of selective and nonselective Pim kinase inhibitors for cancer therapy. J. Med. Chem., 55 (19): 8199-208. [PMID:22924342]

7. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc. Natl. Acad. Sci. U.S.A., 104 (51): 20523-8. [PMID:18077363]

8. 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]

9. Garcia PD, Langowski JL, Wang Y, Chen M, Castillo J, Fanton C, Ison M, Zavorotinskaya T, Dai Y, Lu J et al.. (2014) Pan-PIM kinase inhibition provides a novel therapy for treating hematologic cancers. Clin. Cancer Res., 20 (7): 1834-45. [PMID:24474669]

10. Haddach M, Michaux J, Schwaebe MK, Pierre F, O'Brien SE, Borsan C, Tran J, Raffaele N, Ravula S, Drygin D et al.. (2012) Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases Inhibitor. ACS Med Chem Lett, 3 (2): 135-9. [PMID:24900437]

11. Pierre F, Stefan E, Nédellec AS, Chevrel MC, Regan CF, Siddiqui-Jain A, Macalino D, Streiner N, Drygin D, Haddach M et al.. (2011) 7-(4H-1,2,4-Triazol-3-yl)benzo[c][2,6]naphthyridines: a novel class of Pim kinase inhibitors with potent cell antiproliferative activity. Bioorg. Med. Chem. Lett., 21 (22): 6687-92. [PMID:21982499]

12. 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]

How to cite this page

PIM family: Pim-2 proto-oncogene, serine/threonine kinase. Last modified on 31/01/2018. Accessed on 13/12/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2159.