Target General Infomation
Target ID
Former ID
Target Name
Protein kinase C, theta type
Gene Name
NPKC-theta; Protein kinase C theta; nPKC-theta; Protein kinase C theta; PRKCQ
Target Type
Clinical Trial
Disease Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25]
Renal transplantation [ICD9: 279.5; ICD10: D89.8]
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non- redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates to the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non- canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1.
BioChemical Class
Target Validation
UniProt ID
EC Number
1XJD; 2ENJ; 2ENN; 2ENZ; 2JED; 4Q9Z; 4RA5
Drugs and Mode of Action
Drug(s) Sotrastaurin acetate Drug Info Phase 2 Renal transplantation [537117]
CDE-6960 Drug Info Terminated Inflammatory disease [548364]
LY-317644 Drug Info Terminated Discovery agent [546513]
RO-320432 Drug Info Terminated Discovery agent [541291], [545975]
Inhibitor 2,3,3-Triphenyl-acrylonitrile Drug Info [528755]
2-(4-Hydroxy-phenyl)-3,3-diphenyl-acrylonitrile Drug Info [528755]
3,3-Bis-(4-hydroxy-phenyl)-2-phenyl-acrylonitrile Drug Info [528755]
3,3-Bis-(4-methoxy-phenyl)-2-phenyl-acrylonitrile Drug Info [528755]
3-(4-Hydroxy-phenyl)-2,3-diphenyl-acrylonitrile Drug Info [528755]
4-cycloheptyliden(4-hydroxyphenyl)methylphenol Drug Info [528755]
4-cyclohexyliden(4-hydroxyphenyl)methylphenol Drug Info [528755]
4-[1-(4-hydroxyphenyl)-3-methyl-1-butenyl]phenol Drug Info [528755]
CDE-6960 Drug Info [548365]
Indolocarbazole analogue Drug Info [526234]
LY-317644 Drug Info [551283]
LY-326449 Drug Info [534154]
Phosphonoserine Drug Info [551393]
Phosphonothreonine Drug Info [551393]
RO-316233 Drug Info [528701]
Ro-32-0557 Drug Info [551264]
RO-320432 Drug Info [551264]
Sotrastaurin acetate Drug Info [537117]
[2,2':5',2'']Terthiophen-4-yl-methanol Drug Info [525575]
[2,2':5',2'']Terthiophene-4,5''-dicarbaldehyde Drug Info [525575]
[2,2':5',2'']Terthiophene-4-carbaldehyde Drug Info [525575]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
KEGG Pathway NF-kappa B signaling pathway
Vascular smooth muscle contraction
Tight junction
T cell receptor signaling pathway
Inflammatory mediator regulation of TRP channels
Adipocytokine signaling pathway
PANTHER Pathway Alzheimer disease-amyloid secretase pathway
Apoptosis signaling pathway
EGF receptor signaling pathway
Endothelin signaling pathway
FGF signaling pathway
Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway
Muscarinic acetylcholine receptor 1 and 3 signaling pathway
T cell activation
VEGF signaling pathway
Wnt signaling pathway
5HT2 type receptor mediated signaling pathway
Histamine H1 receptor mediated signaling pathway
Oxytocin receptor mediated signaling pathway
Thyrotropin-releasing hormone receptor signaling pathway
CCKR signaling map ST
Pathway Interaction Database Endothelins
TCR signaling in na&amp
ve CD4+ T cells
Calcineurin-regulated NFAT-dependent transcription in lymphocytes
TCR signaling in na&amp
ve CD8+ T cells
Thromboxane A2 receptor signaling
Role of Calcineurin-dependent NFAT signaling in lymphocytes
Downstream signaling in na&amp
Reactome Apoptotic cleavage of cellular proteins
Effects of PIP2 hydrolysis
Inactivation, recovery and regulation of the phototransduction cascade
FCERI mediated NF-kB activation
G alpha (z) signalling events
WikiPathways TCR Signaling Pathway
Calcium Regulation in the Cardiac Cell
Insulin Signaling
Wnt Signaling Pathway
Wnt Signaling Pathway and Pluripotency
G Protein Signaling Pathways
Myometrial Relaxation and Contraction Pathways
Fc epsilon receptor (FCERI) signaling
Corticotropin-releasing hormone
Signaling Pathways in Glioblastoma
miRs in Muscle Cell Differentiation
TCR signaling
Netrin-1 signaling
GPCR downstream signaling
Effects of PIP2 hydrolysis
Apoptotic execution phase
Ref 537117Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
Ref 541291( 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: 6034).
Ref 545975Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005586)
Ref 546513Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008685)
Ref 548364Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025002)
Ref 525575Bioorg Med Chem Lett. 1999 Aug 2;9(15):2279-82.Novel protein kinase C inhibitors: synthesis and PKC inhibition of beta-substituted polythiophene derivatives.
Ref 526234Bioorg Med Chem Lett. 2002 Jan 21;12(2):147-50.Mixed lineage kinase activity of indolocarbazole analogues.
Ref 528701J Med Chem. 1992 Jan;35(1):177-84.Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides.
Ref 528755J Med Chem. 1992 Feb 7;35(3):573-83.Multivariate analysis by the minimum spanning tree method of the structural determinants of diphenylethylenes and triphenylacrylonitriles implicated in estrogen receptor binding, protein kinase C activity, and MCF7 cell proliferation.
Ref 534154J Med Chem. 1996 Jul 5;39(14):2664-71.(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)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta.
Ref 537117Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
Ref 548365Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025002)
Ref 551264Bisindolylmaleimide inhibitors of protein kinase C. Further conformational restriction of a tertiary amine side chain, Bioorg. Med. Chem. Lett. 4(11):1303-1308 (1994).
Ref 551283Synthesis of bisindolylmaleimide macrocycles, Bioorg. Med. Chem. Lett. 5(18):2093-2096 (1995).
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 1587926URL: The ChEMBL database in 2017

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