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Pim-3 proto-oncogene, serine/threonine kinase

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Target not currently curated in GtoImmuPdb

Target id: 2160

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

Abbreviated Name: Pim3

Family: PIM family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 326 22q13.33 PIM3 Pim-3 proto-oncogene, serine/threonine kinase
Mouse - 326 15 E3 Pim3 proviral integration site 3
Rat - 326 7q34 Pim3 Pim-3 proto-oncogene, serine/threonine kinase
Previous and Unofficial Names Click here for help
KID-1/kinase induced by depolarization | kinase induced by depolarization | pim-3 oncogene | Pim-3 proto-oncogene
Database Links Click here for help
Alphafold Q86V86 (Hs), P58750 (Mm), O70444 (Rn)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL5407 (Hs), CHEMBL3638335 (Rn)
Ensembl Gene ENSG00000198355 (Hs), ENSMUSG00000035828 (Mm), ENSRNOG00000029698 (Rn)
Entrez Gene 415116 (Hs), 223775 (Mm), 64534 (Rn)
Human Protein Atlas ENSG00000198355 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:415116 (Hs), mmu:223775 (Mm), rno:64534 (Rn)
OMIM 610580 (Hs)
Pharos Q86V86 (Hs)
RefSeq Nucleotide NM_001001852 (Hs), NM_145478 (Mm), NM_022602 (Rn)
RefSeq Protein NP_001001852 (Hs), NP_663453 (Mm), NP_072124 (Rn)
SynPHARM 81577 (in complex with compound 20 [PMID: 22136433])
UniProtKB Q86V86 (Hs), P58750 (Mm), O70444 (Rn)
Wikipedia PIM3 (Hs)
Selected 3D Structures Click here for help
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:  12
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 12.1 pKi 10
⤷ pKi 12.1 (Ki 8x10-13 M) [10]
Description: Assayed at 40μM ATP
PIM447 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 11.1 pKi 3
⤷ pKi 11.1 (Ki 9x10-12 M) [3]
GDC-0339 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 10.7 pKi 15
⤷ pKi 10.7 (Ki 2x10-11 M) [15]
AZD1208 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.6 pKi 2
⤷ pKi 9.6 (Ki 2.3x10-10 M) [2]
nuvisertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pKi 8
⤷ pKi 7.4 (Ki 4.2x10-8 M) [8]
uzansertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.9 pIC50 13
⤷ pIC50 9.9 (IC50 1.2x10-10 M) [13]
Description: Kinase inhibition in a biochemical enzyme activity assay.
CX-6258 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pIC50 11
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [11]
SGI-1776 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 7
⤷ pIC50 7.2 (IC50 6.9x10-8 M) [7]
compound 14k [PMID: 21982499] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 14
⤷ pIC50 7.1 (IC50 8.6x10-8 M) [14]
compound 20 [PMID: 22136433] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 12
⤷ pIC50 7.1 (IC50 9x10-8 M) [12]
compound 1a [PMID: 24900749] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pIC50 6
⤷ pIC50 6.8 (IC50 1.5x10-7 M) [6]
dapolsertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition - - 4
⤷ [4]
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: 5,16
Key to terms and symbols Click column headers to sort
Target used in screen: PIM3
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.3 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.7 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
masitinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.1 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
GSK-461364A Small molecule or natural product Hs Inhibitor Inhibition 6.0 pKd
enzastaurin Small molecule or natural product 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 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: 1,9
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 Small molecule or natural product Hs Inhibitor Inhibition 0.2 38.0 45.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.6 4.0 0.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 1.8 31.0 5.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.9 22.0 5.0
JNK inhibitor V Small molecule or natural product Hs Inhibitor Inhibition 3.7 45.0 9.0
isogranulatimide Small molecule or natural product Hs Inhibitor Inhibition 4.5 14.0 17.0
Cdk4 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 4.7 29.0 14.0
STO609 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.0 15.0 1.0
Gö 6983 Small molecule or natural product Hs Inhibitor Inhibition 5.0 57.0 17.0
JAK3 inhibitor VI Small molecule or natural product 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. 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.

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. 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]

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. 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]

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. 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 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]

16. 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 06/03/2024. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2160.