Target Information

Target General Infomation
Target ID
T40276
Former ID
TTDC00163
Target Name
Protein kinase C, beta type
Gene Name
PRKCB
Synonyms
PKC-B; PKC-beta; Protein Kinase C beta; PRKCB
Target Type
Clinical Trial
Disease Brain cancer; Central nervous system tumors [ICD9: 191; ICD10: C71]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Glioblastoma multiforme [ICD9: 191; ICD10: C71]
Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26]
Lymphoma [ICD9: 202.8, 208.9; ICD10: C81-C86]
Non-hodgkin's lymphoma [ICD10: C85]
Renal transplantation [ICD9: 279.5; ICD10: D89.8]
Function
This is a calcium-activated, phospholipid-dependent, serine- and threonine-specific enzyme. Pkc is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. Pkc also serves as the receptor for phorbol esters.
BioChemical Class
Kinase
Target Validation
T40276
UniProt ID
P05771
EC Number
EC 2.7.11.13
Sequence
MADPAAGPPPSEGEESTVRFARKGALRQKNVHEVKNHKFTARFFKQPTFCSHCTDFIWGF
GKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPASDDPRSKHKFKIHTYSSPTFCDHCGS
LLYGLIHQGMKCDTCMMNVHKRCVMNVPSLCGTDHTERRGRIYIQAHIDRDVLIVLVRDA
KNLVPMDPNGLSDPYVKLKLIPDPKSESKQKTKTIKCSLNPEWNETFRFQLKESDKDRRL
SVEIWDWDLTSRNDFMGSLSFGISELQKASVDGWFKLLSQEEGEYFNVPVPPEGSEANEE
LRQKFERAKISQGTKVPEEKTTNTVSKFDNNGNRDRMKLTDFNFLMVLGKGSFGKVMLSE
RKGTDELYAVKILKKDVVIQDDDVECTMVEKRVLALPGKPPFLTQLHSCFQTMDRLYFVM
EYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHI
KIADFGMCKENIWDGVTTKTFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAP
FEGEDEDELFQSIMEHNVAYPKSMSKEAVAICKGLMTKHPGKRLGCGPEGERDIKEHAFF
RYIDWEKLERKEIQPPYKPKARDKRDTSNFDKEFTRQPVELTPTDKLFIMNLDQNEFAGF
SYTNPEFVINV
Drugs and Mode of Action
Drug(s) Enzastaurin Drug Info Phase 3 Non-hodgkin's lymphoma [529450], [537114], [541035]
RUBOXISTAURIN HYDROCHLORIDE Drug Info Phase 3 Lymphoma [528812]
Enzastaurin Drug Info Phase 2 Glioblastoma multiforme [537114], [541035]
LY333531 Drug Info Phase 2 Cancer [522041]
Sotrastaurin acetate Drug Info Phase 2 Renal transplantation [537117]
Enzastaurin Drug Info Phase 1 Brain cancer; Central nervous system tumors [537114], [541035]
BALANOL Drug Info Terminated Discovery agent [542983], [545589]
LY-317644 Drug Info Terminated Discovery agent [546513]
RO-320432 Drug Info Terminated Discovery agent [541291], [545975]
Inhibitor (-)-Cercosporamide Drug Info [529887]
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-(1H-Indol-3-yl)-4-phenylamino-pyrrole-2,5-dione Drug Info [527221]
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-cyclopentyliden(4-hydroxyphenyl)methylphenol Drug Info [528755]
4-[1-(4-hydroxyphenyl)-3-methyl-1-butenyl]phenol Drug Info [528755]
BALANOL Drug Info [551285]
Go 6983 Drug Info [534191]
Indolocarbazole analogue Drug Info [526234]
K00248 Drug Info [527221]
LY-317644 Drug Info [551283]
LY-326449 Drug Info [534154]
LY333531 Drug Info [535082], [535683], [538038]
Molecule 26 Drug Info [535441]
O-Phosphoethanolamine Drug Info [551393]
PROSTRATIN Drug Info [527606]
PUNICAFOLIN Drug Info [551233]
RO-316233 Drug Info [528701]
Ro-32-0557 Drug Info [551264]
RO-320432 Drug Info [551264]
Sotrastaurin acetate Drug Info [537117]
TANNIN Drug Info [551233]
[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]
Modulator Enzastaurin Drug Info [529450]
RUBOXISTAURIN HYDROCHLORIDE Drug Info [528812]
Pathways
KEGG Pathway MAPK signaling pathway
ErbB signaling pathway
Ras signaling pathway
Rap1 signaling pathway
Calcium signaling pathway
Chemokine signaling pathway
NF-kappa B signaling pathway
HIF-1 signaling pathway
Phosphatidylinositol signaling system
Sphingolipid signaling pathway
mTOR signaling pathway
Vascular smooth muscle contraction
Wnt signaling pathway
VEGF signaling pathway
Focal adhesion
Tight junction
Gap junction
Natural killer cell mediated cytotoxicity
B cell receptor signaling pathway
Fc epsilon RI signaling pathway
Fc gamma R-mediated phagocytosis
Leukocyte transendothelial migration
Circadian entrainment
Long-term potentiation
Retrograde endocannabinoid signaling
Glutamatergic synapse
Cholinergic synapse
Serotonergic synapse
GABAergic synapse
Dopaminergic synapse
Long-term depression
Inflammatory mediator regulation of TRP channels
Insulin secretion
GnRH signaling pathway
Melanogenesis
Thyroid hormone synthesis
Thyroid hormone signaling pathway
Oxytocin signaling pathway
Aldosterone-regulated sodium reabsorption
Endocrine and other factor-regulated calcium reabsorption
Salivary secretion
Gastric acid secretion
Pancreatic secretion
Carbohydrate digestion and absorption
Amphetamine addiction
Morphine addiction
Vibrio cholerae infection
Leishmaniasis
African trypanosomiasis
Amoebiasis
Hepatitis B
Influenza A
Pathways in cancer
Proteoglycans in cancer
MicroRNAs in cancer
Glioma
Non-small cell lung cancer
Choline metabolism in cancer
NetPath Pathway IL2 Signaling Pathway
PANTHER Pathway Alzheimer disease-amyloid secretase pathway
Angiogenesis
Apoptosis signaling pathway
B cell activation
EGF receptor signaling pathway
Endothelin signaling pathway
FGF signaling pathway
Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway
Inflammation mediated by chemokine and cytokine signaling pathway
Metabotropic glutamate receptor group I pathway
Muscarinic acetylcholine receptor 1 and 3 signaling pathway
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 Fc-epsilon receptor I signaling in mast cells
TCR signaling in na&amp
#xef
ve CD4+ T cells
TCR signaling in na&amp
ve CD8+ T cells
IL2-mediated signaling events
Ras signaling in the CD4+ TCR pathway
JNK signaling in the CD4+ TCR pathway
Regulation of Ras family activation
Downstream signaling in na&amp
Reactome Disinhibition of SNARE formation
Activation of NF-kappaB in B cells
Trafficking of GluR2-containing AMPA receptors
G alpha (z) signalling events
Depolymerisation of the Nuclear Lamina
WNT5A-dependent internalization of FZD4
VEGFR2 mediated cell proliferation
Response to elevated platelet cytosolic Ca2+
WikiPathways Calcium Regulation in the Cardiac Cell
Insulin Signaling
EGF/EGFR Signaling Pathway
Wnt Signaling Pathway
Wnt Signaling Pathway and Pluripotency
MAPK Signaling Pathway
Wnt Signaling Pathway Netpath
G Protein Signaling Pathways
Kit receptor signaling pathway
Myometrial Relaxation and Contraction Pathways
Signaling by the B Cell Receptor (BCR)
Oncostatin M Signaling Pathway
Corticotropin-releasing hormone
AGE/RAGE pathway
B Cell Receptor Signaling Pathway
Signaling Pathways in Glioblastoma
miRs in Muscle Cell Differentiation
Response to elevated platelet cytosolic Ca2+
MicroRNAs in cardiomyocyte hypertrophy
Physiological and Pathological Hypertrophy of the Heart
References
Ref 522041ClinicalTrials.gov (NCT00482976) Effect of LY333531 on Vascular and Neural Functions. U.S. National Institutes of Health.
Ref 528812Ruboxistaurin: LY 333531. Drugs R D. 2007;8(3):193-9.
Ref 529450The oral protein-kinase C beta inhibitor enzastaurin (LY317615) suppresses signalling through the AKT pathway, inhibits proliferation and induces apoptosis in multiple myeloma cell lines. Leuk Lymphoma. 2008 Jul;49(7):1374-83.
Ref 537114Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
Ref 537117Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
Ref 541035(http://www.guidetopharmacology.org/) 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: 5693).
Ref 541291(http://www.guidetopharmacology.org/) 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 542983(http://www.guidetopharmacology.org/) 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: 8142).
Ref 545589Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003814)
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 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 527221Bioorg Med Chem Lett. 2004 Oct 18;14(20):5171-4.Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors.
Ref 527606J Med Chem. 1992 May 29;35(11):1978-86.A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1.
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 528812Ruboxistaurin: LY 333531. Drugs R D. 2007;8(3):193-9.
Ref 529450The oral protein-kinase C beta inhibitor enzastaurin (LY317615) suppresses signalling through the AKT pathway, inhibits proliferation and induces apoptosis in multiple myeloma cell lines. Leuk Lymphoma. 2008 Jul;49(7):1374-83.
Ref 529887Bioorg Med Chem Lett. 2009 Feb 1;19(3):724-6. Epub 2008 Dec 11.(-)-Cercosporamide derivatives as novel antihyperglycemic agents.
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 534191Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes. FEBS Lett. 1996 Aug 26;392(2):77-80.
Ref 535082Protein kinase C activation and its pharmacological inhibition in vascular disease. Vasc Med. 2000;5(3):173-85.
Ref 535441Potential new medical therapies for diabetic retinopathy: protein kinase C inhibitors. Am J Ophthalmol. 2002 May;133(5):693-8.
Ref 535683Protein kinase C beta inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension. Diabetes. 2003 Feb;52(2):512-8.
Ref 537117Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
Ref 538038Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats. J Clin Invest. 1997 Jul 1;100(1):115-26.
Ref 551233Tannins as selective inhibitors of protein kinase C, Bioorg. Med. Chem. Lett. 2(3):239-244 (1992).
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 551285Evaluation of differential hypoxic cytotoxicity and electrochemical studies of nitro 5-deazaflavins, Bioorg. Med. Chem. Lett. 5(18):2155-2160 (1995).
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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