Pim-1 proto-oncogene, serine/threonine kinase | PIM family | IUPHAR/BPS Guide to PHARMACOLOGY

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Pim-1 proto-oncogene, serine/threonine kinase

Target not currently curated in GtoImmuPdb

Target id: 2158

Nomenclature: Pim-1 proto-oncogene, serine/threonine kinase

Abbreviated Name: Pim1

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 313 6p21 PIM1 Pim-1 proto-oncogene, serine/threonine kinase
Mouse - 313 17 A3.3 Pim1 proviral integration site 1
Rat - 313 20 p12 Pim1 Pim-1 proto-oncogene, serine/threonine kinase
Previous and Unofficial Names
proto-oncogene serine/threonine-protein kinase pim-1 | proviral integration site 1 | pim-1 oncogene | Pim-1 proto-oncogene
Database Links
BRENDA
ChEMBL Target
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:  The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors
PDB Id:  3R04
Resolution:  1.7Å
Species:  Human
References:  20
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of hPim-1 kinase at 2.1 A resolution
PDB Id:  1XQZ
Resolution:  2.1Å
Species:  Human
References:  17
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of hPIM1 bound to PIM447.
PDB Id:  5DWR
Ligand:  PIM447
Resolution:  2.0Å
Species:  Human
References:  4
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human PIM1 in complex with LY-333531 (ruboxistaurin).
PDB Id:  2J2I
Ligand:  ruboxistaurin
Resolution:  1.9Å
Species:  Human
References:  8
Image of receptor 3D structure from RCSB PDB
Description:  Pim1 Complexed with a pyridylcarboxamide
PDB Id:  4N70
Ligand:  LGB321
Resolution:  2.1Å
Species:  Human
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human Pim-1 kinase in complex with a quinazolinone-pyrrolodihydropyrrolone inhibitor
PDB Id:  6MT0
Ligand:  compound 28 [PMID: 30624936]
Resolution:  2.2Å
Species:  Human
References:  18
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 Value Parameter Reference
LGB321 Hs Inhibition 12.0 pKi 10
pKi 12.0 (Ki 1x10-12 M) [10]
Description: Assayed at 400μM ATP
PIM447 Hs Inhibition 11.2 pKi 4
pKi 11.2 (Ki 6x10-12 M) [4]
AZD1208 Hs Inhibition 10.8 pKi 3
pKi 10.8 (Ki 1.7x10-11 M) [3]
leucettine L41 Hs Inhibition 8.4 pIC50 6
pIC50 8.4 (IC50 4.1x10-9 M) [6]
compound 14k [PMID: 21982499] Hs Inhibition 8.3 pIC50 16
pIC50 8.3 (IC50 5x10-9 M) [16]
CX-6258 Hs Inhibition 8.3 pIC50 11
pIC50 8.3 (IC50 5x10-9 M) [11]
SGI-1776 Hs Inhibition 8.1 pIC50 7
pIC50 8.1 (IC50 7x10-9 M) [7]
XL413 Hs Inhibition 7.4 pIC50 13
pIC50 7.4 (IC50 4.2x10-8 M) [13]
compound 28 [PMID: 30624936] Hs Inhibition 7.3 pIC50 18
pIC50 7.3 (IC50 5x10-8 M) [18]
compound 20 [PMID: 22136433] Hs Inhibition 7.2 pIC50 12
pIC50 7.2 (IC50 6x10-8 M) [12]
voruciclib Hs Inhibition 7.1 pIC50 15
pIC50 7.1 (IC50 7.2x10-8 M) [15]
ruboxistaurin Hs Inhibition 6.7 pIC50 8
pIC50 6.7 (IC50 2x10-7 M) [8]
silmitasertib Hs Inhibition 6.7 pIC50 2
pIC50 6.7 (IC50 2.16x10-7 M) [2]
compound 2 [PMID: 22560567] Hs Inhibition 6.5 pIC50 13
pIC50 6.5 (IC50 3.32x10-7 M) [13]
Akt inhibitor X Hs Inhibition 5.9 pIC50 14
pIC50 5.9 (IC50 1.28x10-6 M) [14]
CX-5011 Hs Inhibition 5.6 pIC50 2
pIC50 5.6 (IC50 2.51x10-6 M) [2]
CX-5279 Hs Inhibition 5.1 pIC50 2
pIC50 5.1 (IC50 8.52x10-6 M) [2]
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: 5,19

Key to terms and symbols Click column headers to sort
Target used in screen: PIM1
Ligand Sp. Type Action Value Parameter
staurosporine Hs Inhibitor Inhibition 8.5 pKd
A-674563 Hs Inhibitor Inhibition 6.7 pKd
lestaurtinib Hs Inhibitor Inhibition 6.7 pKd
enzastaurin Hs Inhibitor Inhibition 6.7 pKd
GSK-461364A Hs Inhibitor Inhibition 6.6 pKd
ruboxistaurin Hs Inhibitor Inhibition 6.6 pKd
alvocidib Hs Inhibitor Inhibition 6.3 pKd
midostaurin Hs Inhibitor Inhibition 6.3 pKd
GSK690693 Hs Inhibitor Inhibition 6.0 pKd
masitinib Hs Inhibitor Inhibition 5.9 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: 1,9

Key to terms and symbols Click column headers to sort
Target used in screen: Pim-1/PIM1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
SB 218078 Hs Inhibitor Inhibition 0.4 -2.0 1.0
isogranulatimide Hs Inhibitor Inhibition 1.4 6.0 2.0
staurosporine Hs Inhibitor Inhibition 1.5 0.5 0.5
GF109203X Hs Inhibitor Inhibition 5.3 1.0 1.0
Cdk4 inhibitor Hs Inhibitor Inhibition 8.8 28.0 13.0
Gö 6983 Hs Inhibitor Inhibition 11.6 11.0 1.0
JNK inhibitor V Hs Inhibitor Inhibition 11.6 15.0 3.0
casein kinase II inhibitor III Hs Inhibitor Inhibition 16.2 49.0 6.0
bisindolylmaleimide IV Hs Inhibitor Inhibition 17.2 12.0 0.0
Cdc2-like kinase inhibitor Hs Inhibitor Inhibition 17.9 25.0 4.0
Displaying the top 10 most potent ligands  View all ligands in screen »

References

Show »

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. Battistutta R, Cozza G, Pierre F, Papinutto E, Lolli G, Sarno S, O'Brien SE, Siddiqui-Jain A, Haddach M, Anderes K et al.. (2011) Unprecedented selectivity and structural determinants of a new class of protein kinase CK2 inhibitors in clinical trials for the treatment of cancer. Biochemistry, 50 (39): 8478-88. [PMID:21870818]

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. Debdab M, Carreaux F, Renault S, Soundararajan M, Fedorov O, Filippakopoulos P, Lozach O, Babault L, Tahtouh T, Baratte B et al.. (2011) Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing. J. Med. Chem., 54 (12): 4172-86. [PMID:21615147]

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. U.S.A., 104 (51): 20523-8. [PMID:18077363]

9. 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]

10. 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]

11. 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]

12. 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]

13. Koltun ES, Tsuhako AL, Brown DS, Aay N, Arcalas A, Chan V, Du H, Engst S, Ferguson K, Franzini M et al.. (2012) Discovery of XL413, a potent and selective CDC7 inhibitor. Bioorg. Med. Chem. Lett., 22 (11): 3727-31. [PMID:22560567]

14. Li W, Wan X, Zeng F, Xie Y, Wang Y, Zhang W, Li L and Huang N. (2014) More than just a GPCR ligand: structure-based discovery of thioridazine derivatives as Pim-1 kinase inhibitors. MedChemComm, 5: 507-511.

15. Paiva C, Godbersen JC, Soderquist RS, Rowland T, Kilmarx S, Spurgeon SE, Brown JR, Srinivasa SP, Danilov AV. (2015) Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells. PLoS ONE, 10 (11): e0143685. [PMID:26606677]

16. 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]

17. Qian KC, Wang L, Hickey ER, Studts J, Barringer K, Peng C, Kronkaitis A, Li J, White A, Mische S et al.. (2005) Structural basis of constitutive activity and a unique nucleotide binding mode of human Pim-1 kinase. J. Biol. Chem., 280 (7): 6130-7. [PMID:15525646]

18. 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]

19. 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]

20. Xiang Y, Hirth B, Asmussen G, Biemann HP, Bishop KA, Good A, Fitzgerald M, Gladysheva T, Jain A, Jancsics K et al.. (2011) The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors. Bioorg. Med. Chem. Lett., 21 (10): 3050-6. [PMID:21507633]

How to cite this page

PIM family: Pim-1 proto-oncogene, serine/threonine kinase. Last modified on 21/01/2019. Accessed on 14/11/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2158.