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protein kinase C alpha

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1482

Nomenclature: protein kinase C alpha

Abbreviated Name: PKCα

Family: Delta subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 672 17q24.2 PRKCA protein kinase C alpha
Mouse - 672 11 70.8 cM Prkca protein kinase C, alpha
Rat - 672 10q32.1 Prkca protein kinase C, alpha
Previous and Unofficial Names Click here for help
PKC-alpha | protein kinase C
Database Links Click here for help
Alphafold P17252 (Hs), P20444 (Mm), P05696 (Rn)
BRENDA 2.7.11.13
CATH/Gene3D 2.60.40.150
ChEMBL Target CHEMBL299 (Hs), CHEMBL2567 (Mm), CHEMBL2855 (Rn)
Ensembl Gene ENSG00000154229 (Hs), ENSMUSG00000050965 (Mm), ENSRNOG00000003491 (Rn)
Entrez Gene 5578 (Hs), 18750 (Mm), 24680 (Rn)
Human Protein Atlas ENSG00000154229 (Hs)
KEGG Enzyme 2.7.11.13
KEGG Gene hsa:5578 (Hs), mmu:18750 (Mm), rno:24680 (Rn)
OMIM 176960 (Hs)
Pharos P17252 (Hs)
RefSeq Nucleotide NM_002737 (Hs), NM_011101 (Mm), NM_001105713 (Rn)
RefSeq Protein NP_002728 (Hs), NP_035231 (Mm), NP_001099183 (Rn)
SynPHARM 80860 (in complex with sotrastaurin)
UniProtKB P17252 (Hs), P20444 (Mm), P05696 (Rn)
Wikipedia PRKCA (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.11.13

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

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ingenol mebutate Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Activation 9.5 pKi 9
⤷ pKi 9.5 (Ki 3x10-10 M) [9]
10-Me-Aplog-1 Small molecule or natural product Click here for species-specific activity table Hs Activation 8.3 pKi 10
⤷ pKi 8.3 (Ki 4.7x10-9 M) [10]
Description: Binding affinity for the C1A domain of PKCα, determined by inhibition of [3H]PDBu binding
RasGRP activator 1 Small molecule or natural product Click here for species-specific activity table Hs Binding 7.8 pKi 6
⤷ pKi 7.8 (Ki 1.62x10-8 M) [6]
Teleocidin B4 Small molecule or natural product Hs Activation - - 8
⤷ [8]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
darovasertib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pIC50 11
⤷ pIC50 8.7 (IC50 1.9x10-9 M) [11]
sotrastaurin Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 16
⤷ pIC50 8.7 (IC50 2.1x10-9 M) [16]
Gö 6976 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.6 pIC50 12
⤷ pIC50 8.6 (IC50 2.3x10-9 M) [12]
Gö 6983 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pIC50 7
⤷ pIC50 8.1 (IC50 7x10-9 M) [7]
Ro-32-0432 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Bt Inhibition 8.0 – 8.1 pIC50 2,17
⤷ pIC50 8.0 – 8.1 (IC50 9.3x10-9 – 9x10-9 M) [2,17]
GF109203X Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Bt Inhibition 7.7 pIC50 15
⤷ pIC50 7.7 (IC50 2x10-8 M) [15]
7-hydroxystaurosporine Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 13
⤷ pIC50 7.5 (IC50 2.9x10-8 M) [13]
balanol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 3
⤷ pIC50 7.5 (IC50 3x10-8 M) [3]
ruboxistaurin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.4 pIC50 14
⤷ pIC50 6.4 (IC50 3.6x10-7 M) [14]
enzastaurin Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.1 pIC50 4
⤷ pIC50 6.1 (IC50 8x10-7 M) [4]
View species-specific inhibitor tables
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: 1,5
Key to terms and symbols Click column headers to sort
Target used in screen: PKCα/PKCa
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.2 0.5 -0.5
Ro-32-0432 Small molecule or natural product Hs Inhibitor Inhibition 2.6
Gö 6983 Small molecule or natural product Hs Inhibitor Inhibition 3.1 -1.0 0.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 1.0 1.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 1.0 3.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 13.9 96.0 98.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 23.7 19.0 0.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 27.7 36.0 14.0
bisindolylmaleimide IV Small molecule or natural product Hs Inhibitor Inhibition 27.7 26.0 4.0
PKCbeta inhibitor Small molecule or natural product Hs Inhibitor Inhibition 32.0 6.0 2.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
PKCα is included in GtoImmuPdb based on its GO immune process associations.

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. Birchall AM, Bishop J, Bradshaw D, Cline A, Coffey J, Elliott LH, Gibson VM, Greenham A, Hallam TJ, Harris W et al.. (1994) Ro 32-0432, a selective and orally active inhibitor of protein kinase C prevents T-cell activation. J Pharmacol Exp Ther, 268 (2): 922-9. [PMID:8114006]

3. Defauw JM, Murphy MM, Jagdmann Jr GE, Hu H, Lampe JW, Hollinshead SP, Mitchell TJ, Crane HM, Heerding JM, Mendoza JS et al.. (1996) Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A. J Med Chem, 39 (26): 5215-27. [PMID:8978850]

4. Faul MM, Gillig JR, Jirousek MR, Ballas LM, Schotten T, Kahl A, Mohr M. (2003) Acyclic N-(azacycloalkyl)bisindolylmaleimides: isozyme selective inhibitors of PKCbeta. Bioorg Med Chem Lett, 13 (11): 1857-9. [PMID:12749884]

5. 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]

6. Garcia LC, Donadío LG, Mann E, Kolusheva S, Kedei N, Lewin NE, Hill CS, Kelsey JS, Yang J, Esch TE et al.. (2014) Synthesis, biological, and biophysical studies of DAG-indololactones designed as selective activators of RasGRP. Bioorg Med Chem, 22 (12): 3123-40. [PMID:24794745]

7. Gschwendt M, Dieterich S, Rennecke J, Kittstein W, Mueller HJ, Johannes FJ. (1996) Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes. FEBS Lett, 392 (2): 77-80. [PMID:8772178]

8. Iseki S, Ikeda H, Kobayashi S, Irie K, Harada H, Kakeya H. (2024) Teleocidin B-4, a PKC Activator, Upregulates Hypoxia-Inducible Factor 1 (HIF-1) Activity by Promoting the Accumulation of HIF-1α Protein via the PKCα/mTORC Signaling Pathway. J Nat Prod, [Epub ahead of print]. DOI: 10.1021/acs.jnatprod.4c00395

9. Kedei N, Lundberg DJ, Toth A, Welburn P, Garfield SH, Blumberg PM. (2004) Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res, 64 (9): 3243-55. [PMID:15126366]

10. Kikumori M, Yanagita RC, Tokuda H, Suzuki N, Nagai H, Suenaga K, Irie K. (2012) Structure-activity studies on the spiroketal moiety of a simplified analogue of debromoaplysiatoxin with antiproliferative activity. J Med Chem, 55 (11): 5614-26. [PMID:22625994]

11. Luzzio MJ, Papillon J, Visser MS. (2016) Protein kinase C inhibitors and methods of their use. Patent number: WO2016020864A1. Assignee: Novartis Ag. Priority date: 06/08/2014. Publication date: 11/02/2016.

12. Martiny-Baron G, Kazanietz MG, Mischak H, Blumberg PM, Kochs G, Hug H, Marmé D, Schächtele C. (1993) Selective inhibition of protein kinase C isozymes by the indolocarbazole Gö 6976. J Biol Chem, 268 (13): 9194-7. [PMID:8486620]

13. Seynaeve CM, Kazanietz MG, Blumberg PM, Sausville EA, Worland PJ. (1994) Differential inhibition of protein kinase C isozymes by UCN-01, a staurosporine analogue. Mol Pharmacol, 45 (6): 1207-14. [PMID:8022414]

14. Tanaka M, Sagawa S, Hoshi J, Shimoma F, Matsuda I, Sakoda K, Sasase T, Shindo M, Inaba T. (2004) Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors. Bioorg Med Chem Lett, 14 (20): 5171-4. [PMID:15380221]

15. Toullec D, Pianetti P, Coste H, Bellevergue P, Grand-Perret T, Ajakane M, Baudet V, Boissin P, Boursier E, Loriolle F et al.. (1991) The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem, 266 (24): 15771-81. [PMID:1874734]

16. Wagner J, von Matt P, Sedrani R, Albert R, Cooke N, Ehrhardt C, Geiser M, Rummel G, Stark W, Strauss A et al.. (2009) Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes. J Med Chem, 52 (20): 6193-6. [PMID:19827831]

17. Wilkinson SE, Parker PJ, Nixon JS. (1993) Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C. Biochem J, 294 ( Pt 2): 335-7. [PMID:8373348]

Contributors

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How to cite this page

Mohib Uddin.
Delta subfamily: protein kinase C alpha. Last modified on 06/06/2024. Accessed on 04/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1482.