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Pim-2 proto-oncogene, serine/threonine kinase

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Target id: 2159

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

Abbreviated Name: Pim2

Family: PIM family

Contents:

Gene and Protein Information Click here for help
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 3.55 cM Pim2 proviral integration site 2
Rat - 311 Xq13 Pim2 Pim-2 proto-oncogene, serine/threonine kinase
Previous and Unofficial Names Click here for help
pim-2 oncogene | Pim-2 proto-oncogene
Database Links Click here for help
Alphafold Q9P1W9 (Hs), Q62070 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL4523 (Hs)
Ensembl Gene ENSG00000102096 (Hs), ENSMUSG00000031155 (Mm), ENSRNOG00000008177 (Rn)
Entrez Gene 11040 (Hs), 18715 (Mm), 317366 (Rn)
Human Protein Atlas ENSG00000102096 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:11040 (Hs), mmu:18715 (Mm), rno:317366 (Rn)
OMIM 300295 (Hs)
Pharos Q9P1W9 (Hs)
RefSeq Nucleotide NM_006875 (Hs), NM_138606 (Mm), NM_001172103 (Rn)
RefSeq Protein NP_006866 (Hs), NP_613072 (Mm), NP_001165574 (Rn)
UniProtKB Q9P1W9 (Hs), Q62070 (Mm)
Wikipedia PIM2 (Hs)
Selected 3D Structures Click here for help
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 Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LGB321 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 11.7 pKi 11
⤷ pKi 11.7 (Ki 2.1x10-12 M) [11]
Description: Assayed at 4μM ATP
PIM447 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 10.7 pKi 4
⤷ pKi 10.7 (Ki 1.8x10-11 M) [4]
GDC-0339 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 10.0 pKi 16
⤷ pKi 10.0 (Ki 1x10-10 M) [16]
AZD1208 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.8 pKi 3
⤷ pKi 9.8 (Ki 1.6x10-10 M) [3]
nuvisertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.6 pKi 9
⤷ pKi 6.6 (Ki 2.39x10-7 M) [9]
compound 14k [PMID: 21982499] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.2 pIC50 14
⤷ pIC50 8.2 (IC50 6x10-9 M) [14]
CX-6258 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 12
⤷ pIC50 7.6 (IC50 2.5x10-8 M) [12]
uzansertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 pIC50 13
⤷ pIC50 7.5 (IC50 3x10-8 M) [13]
Description: Kinase inhibition in a biochemical enzyme activity assay.
compound 28 [PMID: 30624936] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 15
⤷ pIC50 7.3 (IC50 5x10-8 M) [15]
SGI-1776 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 7
⤷ pIC50 6.4 (IC50 3.63x10-7 M) [7]
ruboxistaurin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition <4.7 pIC50 8
⤷ pIC50 <4.7 (IC50 >2x10-5 M) [8]
dapolsertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition - - 5
⤷ [5]
DiscoveRx KINOMEscan® screen Click here for help
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: 6,17
Key to terms and symbols Click column headers to sort
Target used in screen: PIM2
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.6 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 6.2 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
enzastaurin Small molecule or natural product Hs Inhibitor Inhibition 6.1 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand 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 Click here for help
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: 1,10
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 Small molecule or natural product Hs Inhibitor Inhibition 1.9 6.0 -2.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 10.4 7.0 0.0
isogranulatimide Small molecule or natural product Hs Inhibitor Inhibition 34.4 5.0 0.0
STO609 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 41.7 14.0 0.0
Cdk4 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 44.6 27.0 6.0
PKR inhibitor, negative control Small molecule or natural product Hs Inhibitor Inhibition 48.6 17.0 3.0
casein kinase II inhibitor III Small molecule or natural product Hs Inhibitor Inhibition 52.8 28.0 1.0
wortmannin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 60.6
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 64.1 15.0 4.0
K-252a Small molecule or natural product 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. Czardybon W, Brzózka K, Galezowski M, Windak R, Milik M, Zawadzka M, Guzik E, Prokop M, Wilik K, Sabiniarz A et al.. (2014) Novel benzimidazole derivatives as kinase inhibitors. Patent number: WO2014096388A2. Assignee: Selvita S.A.. Priority date: 20/12/2013. Publication date: 26/06/2014.

6. 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]

7. 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]

8. 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 USA, 104 (51): 20523-8. [PMID:18077363]

9. Foulks JM, Carpenter KJ, Luo B, Xu Y, Senina A, Nix R, Chan A, Clifford A, Wilkes M, Vollmer D et al.. (2014) A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia, 16 (5): 403-12. [PMID:24953177]

10. 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]

11. 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]

12. 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]

13. Koblish H, Li YL, Shin N, Hall L, Wang Q, Wang K, Covington M, Marando C, Bowman K, Boer J et al.. (2018) Preclinical characterization of INCB053914, a novel pan-PIM kinase inhibitor, alone and in combination with anticancer agents, in models of hematologic malignancies. PLoS ONE, 13 (6): e0199108. [PMID:29927999]

14. 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]

15. Wang HL, Andrews KL, Booker SK, Canon J, Cee VJ, Chavez Jr F, Chen Y, Eastwood H, Guerrero N, Herberich B et al.. (2019) Discovery of ( R)-8-(6-Methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4- b]pyrrol-2-yl)-3-(1-methylcyclopropyl)-2-((1-methylcyclopropyl)amino)quinazolin-4(3 H)-one, a Potent and Selective Pim-1/2 Kinase Inhibitor for Hematological Malignancies. J Med Chem, 62 (3): 1523-1540. [PMID:30624936]

16. Wang X, Blackaby W, Allen V, Chan GKY, Chang JH, Chiang PC, Diène C, Drummond J, Do S, Fan E et al.. (2019) Optimization of Pan-Pim Kinase Activity and Oral Bioavailability Leading to Diaminopyrazole (GDC-0339) for the Treatment of Multiple Myeloma. J Med Chem, 62 (4): 2140-2153. [PMID:30715878]

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]

How to cite this page

PIM family: Pim-2 proto-oncogene, serine/threonine kinase. Last modified on 06/03/2024. Accessed on 06/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2159.