Target General Infomation
Target ID
T44861 (Former ID: TTDNC00553)
Target Name
Protein kinase C delta (PRKCD)
nPKC-delta; Tyrosine-protein kinase PRKCD; SDK1; Protein kinase C delta type catalytic subunit; Protein kinase C delta type; PKC-delta
Gene Name
Target Type
Clinical trial target
Disease [+] 1 Target-related Diseases +
1 Myocardial infarction [ICD-11: BA41-BA43]
Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion. Phosphorylates ELAVL1 in response to angiotensin-2 treatment. Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses.
BioChemical Class
UniProt ID
EC Number
Drugs and Modes of Action
Clinical Trial Drug(s) [+] 1 Clinical Trial Drugs +
1 KAI-9803 Drug Info Phase 1/2 Acute myocardial infarction [2], [3]
Mode of Action [+] 2 Modes of Action +
Inhibitor [+] 24 Inhibitor drugs +
1 KAI-9803 Drug Info [1], [4], [5]
2 LY-317644 Drug Info [7]
3 RO-320432 Drug Info [8]
4 13-Acetylphorbol Drug Info [9]
5 2,3,3-Triphenyl-acrylonitrile Drug Info [10]
6 2-(4-Hydroxy-phenyl)-3,3-diphenyl-acrylonitrile Drug Info [10]
7 3,3-Bis-(4-hydroxy-phenyl)-2-phenyl-acrylonitrile Drug Info [10]
8 3,3-Bis-(4-methoxy-phenyl)-2-phenyl-acrylonitrile Drug Info [10]
9 3-(4-Hydroxy-phenyl)-2,3-diphenyl-acrylonitrile Drug Info [10]
10 4-cycloheptyliden(4-hydroxyphenyl)methylphenol Drug Info [10]
11 4-cyclohexyliden(4-hydroxyphenyl)methylphenol Drug Info [10]
12 4-[1-(4-hydroxyphenyl)-3-methyl-1-butenyl]phenol Drug Info [10]
13 INDOLACTUM Drug Info [11]
14 Indolocarbazole analogue Drug Info [12]
15 Ingenol-3-bezoate Drug Info [13]
16 LY-326449 Drug Info [14]
17 Phorbol 12,13-butyrate Drug Info [15]
18 PROSTRATIN Drug Info [16]
19 RO-316233 Drug Info [17]
20 Ro-32-0557 Drug Info [8]
21 THYMELEATOXIN Drug Info [13]
22 [2,2':5',2'']Terthiophen-4-yl-methanol Drug Info [18]
23 [2,2':5',2'']Terthiophene-4,5''-dicarbaldehyde Drug Info [18]
24 [2,2':5',2'']Terthiophene-4-carbaldehyde Drug Info [18]
Activator [+] 1 Activator drugs +
1 AD 198 Drug Info [6]
Target Regulators
Target-regulating microRNAs
Target-interacting Proteins
Target Profiles in Patients
Target Expression
 Profile (TEP)
Target Affiliated Biological Pathways
KEGG Pathway [+] 10 KEGG Pathways +
1 Chemokine signaling pathway
2 Vascular smooth muscle contraction
3 Tight junction
4 Fc epsilon RI signaling pathway
5 Fc gamma R-mediated phagocytosis
6 Neurotrophin signaling pathway
7 Inflammatory mediator regulation of TRP channels
8 GnRH signaling pathway
9 Estrogen signaling pathway
10 Type II diabetes mellitus
NetPath Pathway [+] 1 NetPath Pathways +
1 IL2 Signaling Pathway
Panther Pathway [+] 17 Panther Pathways +
1 Alpha adrenergic receptor signaling pathway
2 Alzheimer disease-amyloid secretase pathway
3 Angiogenesis
4 Apoptosis signaling pathway
5 B cell activation
6 EGF receptor signaling pathway
7 Endothelin signaling pathway
8 FGF signaling pathway
9 Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway
10 Muscarinic acetylcholine receptor 1 and 3 signaling pathway
11 VEGF signaling pathway
12 Wnt signaling pathway
13 5HT2 type receptor mediated signaling pathway
14 Histamine H1 receptor mediated signaling pathway
15 Oxytocin receptor mediated signaling pathway
16 Thyrotropin-releasing hormone receptor signaling pathway
17 CCKR signaling map ST
PID Pathway [+] 20 PID Pathways +
1 Endothelins
2 LPA receptor mediated events
3 Thromboxane A2 receptor signaling
4 Role of Calcineurin-dependent NFAT signaling in lymphocytes
5 IGF1 pathway
6 Ceramide signaling pathway
7 IFN-gamma pathway
8 ErbB1 downstream signaling
9 Syndecan-4-mediated signaling events
10 IL6-mediated signaling events
11 PDGFR-beta signaling pathway
12 Hedgehog signaling events mediated by Gli proteins
13 Signaling events mediated by VEGFR1 and VEGFR2
14 PAR1-mediated thrombin signaling events
15 Syndecan-2-mediated signaling events
16 Validated transcriptional targets of TAp63 isoforms
17 p53 pathway
18 Trk receptor signaling mediated by the MAPK pathway
19 Trk receptor signaling mediated by PI3K and PLC-gamma
20 Alpha-synuclein signaling
Reactome [+] 10 Reactome Pathways +
1 Apoptotic cleavage of cellular proteins
2 Calmodulin induced events
3 Effects of PIP2 hydrolysis
4 DAG and IP3 signaling
5 Role of phospholipids in phagocytosis
6 G alpha (z) signalling events
7 HuR (ELAVL1) binds and stabilizes mRNA
8 VEGFR2 mediated cell proliferation
9 CLEC7A (Dectin-1) signaling
10 Interferon gamma signaling
WikiPathways [+] 26 WikiPathways +
1 TCR Signaling Pathway
2 Type II interferon signaling (IFNG)
3 Calcium Regulation in the Cardiac Cell
4 Insulin Signaling
5 EGF/EGFR Signaling Pathway
6 Wnt Signaling Pathway
7 Wnt Signaling Pathway and Pluripotency
8 MAPK Signaling Pathway
9 IL-6 signaling pathway
10 G Protein Signaling Pathways
11 Myometrial Relaxation and Contraction Pathways
12 Regulation of mRNA Stability by Proteins that Bind AU-rich Elements
13 DAG and IP3 signaling
14 Alpha 6 Beta 4 signaling pathway
15 BDNF signaling pathway
16 Oncostatin M Signaling Pathway
17 Corticotropin-releasing hormone
18 AGE/RAGE pathway
19 B Cell Receptor Signaling Pathway
20 Signaling Pathways in Glioblastoma
21 miRs in Muscle Cell Differentiation
22 Opioid Signalling
23 GPCR downstream signaling
24 Effects of PIP2 hydrolysis
25 Apoptotic execution phase
26 Type II diabetes mellitus
Target-Related Models and Studies
Target Validation
REF 1 PKC delta and epsilon in drug targeting and therapeutics. Recent Pat DNA Gene Seq. 2009;3(2):96-101.
REF 2 URL: Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7840).
REF 3 Pharmacologic therapeutics for cardiac reperfusion injury. Expert Opin Emerg Drugs. 2007 Sep;12(3):367-88.
REF 4 Letter by Metzler et al regarding article, "Intracoronary KAI-9803 as an adjunct to primary coronary intervention for acute ST-segment elevation myocardial infarction". Circulation. 2008 Jul 22;118(4):e80.
REF 5 Intracoronary KAI-9803 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction. Circulation. 2008 Feb 19;117(7):886-96.
REF 6 Novel extranuclear-targeted anthracyclines override the antiapoptotic functions of Bcl-2 and target protein kinase C pathways to induce apoptosis. Mol Cancer Ther. 2002 May;1(7):469-81.
REF 7 Synthesis of bisindolylmaleimide macrocycles, Bioorg. Med. Chem. Lett. 5(18):2093-2096 (1995).
REF 8 Bisindolylmaleimide inhibitors of protein kinase C. Further conformational restriction of a tertiary amine side chain, Bioorg. Med. Chem. Lett. 4(11):1303-1308 (1994).
REF 9 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
REF 10 Multivariate analysis by the minimum spanning tree method of the structural determinants of diphenylethylenes and triphenylacrylonitriles implicate... J Med Chem. 1992 Feb 7;35(3):573-83.
REF 11 Structural basis of RasGRP binding to high-affinity PKC ligands. J Med Chem. 2002 Feb 14;45(4):853-60.
REF 12 Mixed lineage kinase activity of indolocarbazole analogues. Bioorg Med Chem Lett. 2002 Jan 21;12(2):147-50.
REF 13 Structural basis of binding of high-affinity ligands to protein kinase C: prediction of the binding modes through a new molecular dynamics method a... J Med Chem. 2001 May 24;44(11):1690-701.
REF 14 (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H... J Med Chem. 1996 Jul 5;39(14):2664-71.
REF 15 Conformationally constrained analogues of diacylglycerol (DAG). 28. DAG-dioxolanones reveal a new additional interaction site in the C1b domain of ... J Med Chem. 2007 Jul 26;50(15):3465-81.
REF 16 A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1. J Med Chem. 1992 May 29;35(11):1978-86.
REF 17 Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides. J Med Chem. 1992 Jan;35(1):177-84.
REF 18 Novel protein kinase C inhibitors: synthesis and PKC inhibition of beta-substituted polythiophene derivatives. Bioorg Med Chem Lett. 1999 Aug 2;9(15):2279-82.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Wang and Dr. Li.