Pim-3 proto-oncogene, serine/threonine kinase | PIM family | IUPHAR/BPS Guide to PHARMACOLOGY

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Pim-3 proto-oncogene, serine/threonine kinase

Target id: 2160

Nomenclature: Pim-3 proto-oncogene, serine/threonine kinase

Abbreviated Name: Pim3

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-3 proto-oncogene, serine/threonine kinase in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 326 22q13 PIM3 Pim-3 proto-oncogene, serine/threonine kinase
Mouse - 326 15 E3 Pim3 proviral integration site 3
Rat - 326 7 q34 Pim3 Pim-3 proto-oncogene, serine/threonine kinase
Previous and Unofficial Names
KID-1/kinase induced by depolarization | kinase induced by depolarization | pim-3 oncogene | Pim-3 proto-oncogene
Database Links
BRENDA
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human proto-oncogene serine threonine kinase (PIM1) in complex with a consensus peptide and a beta carboline ligand II.
PDB Id:  3CY2
Ligand:  compound 20 [PMID: 22136433]
Resolution:  2.01Å
Species:  Human
References:  10
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 12.1 pKi 8
pKi 12.1 (Ki 8x10-13 M) [8]
Description: Assayed at 40μM ATP
PIM447 Hs Inhibition 11.1 pKi 3
pKi 11.1 (Ki 9x10-12 M) [3]
AZD1208 Hs Inhibition 9.6 pKi 2
pKi 9.6 (Ki 2.3x10-10 M) [2]
CX-6258 Hs Inhibition 7.8 pIC50 9
pIC50 7.8 (IC50 1.6x10-8 M) [9]
SGI-1776 Hs Inhibition 7.2 pIC50 6
pIC50 7.2 (IC50 6.9x10-8 M) [6]
compound 14k [PMID: 21982499] Hs Inhibition 7.1 pIC50 11
pIC50 7.1 (IC50 8.6x10-8 M) [11]
compound 20 [PMID: 22136433] Hs Inhibition 7.1 pIC50 10
pIC50 7.1 (IC50 9x10-8 M) [10]
compound 1a [PMID: 24900749] Hs Inhibition 6.8 pIC50 5
pIC50 6.8 (IC50 1.5x10-7 M) [5]
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: 4,12

Key to terms and symbols Click column headers to sort
Target used in screen: PIM3
Ligand Sp. Type Action Affinity Units
staurosporine Hs Inhibitor Inhibition 9.3 pKd
ruboxistaurin Hs Inhibitor Inhibition 7.9 pKd
lestaurtinib Hs Inhibitor Inhibition 7.7 pKd
A-674563 Hs Inhibitor Inhibition 6.8 pKd
midostaurin Hs Inhibitor Inhibition 6.3 pKd
alvocidib Hs Inhibitor Inhibition 6.2 pKd
masitinib Hs Inhibitor Inhibition 6.1 pKd
GSK690693 Hs Inhibitor Inhibition 6.1 pKd
enzastaurin Hs Inhibitor Inhibition 6.0 pKd
GSK-461364A Hs Inhibitor Inhibition 6.0 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: 1,7

Key to terms and symbols Click column headers to sort
Target used in screen: Pim-3/PIM3
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
SB 218078 Hs Inhibitor Inhibition 0.2 38.0 45.0
staurosporine Hs Inhibitor Inhibition 0.6 4.0 0.0
K-252a Hs Inhibitor Inhibition 1.8 31.0 5.0
GF109203X Hs Inhibitor Inhibition 1.9 22.0 5.0
JNK inhibitor V Hs Inhibitor Inhibition 3.7 45.0 9.0
isogranulatimide Hs Inhibitor Inhibition 4.5 14.0 17.0
Cdk4 inhibitor Hs Inhibitor Inhibition 4.7 29.0 14.0
STO609 Hs Inhibitor Inhibition 5.0 15.0 1.0
Gö 6983 Hs Inhibitor Inhibition 5.0 57.0 17.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 7.6 63.0 22.0
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. 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]

3. 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]

4. 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]

5. Dowling JE, Alimzhanov M, Bao L, Block MH, Chuaqui C, Cooke EL, Denz CR, Hird A, Huang S, Larsen NA et al.. (2013) Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of CK2 Kinase with Activity in Vivo. ACS Med Chem Lett, 4 (8): 800-5. [PMID:24900749]

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. 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]

8. 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]

9. 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]

10. Huber K, Brault L, Fedorov O, Gasser C, Filippakopoulos P, Bullock AN, Fabbro D, Trappe J, Schwaller J, Knapp S et al.. (2012) 7,8-dichloro-1-oxo-β-carbolines as a versatile scaffold for the development of potent and selective kinase inhibitors with unusual binding modes. J. Med. Chem., 55 (1): 403-13. [PMID:22136433]

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-3 proto-oncogene, serine/threonine kinase. Last modified on 31/01/2018. Accessed on 17/12/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2160.