PRKCB

Summary

PRKCB (protein kinase C beta, HGNC:9395) is a protein-coding gene on chromosome 16p12.2-p12.1, encoding Protein kinase C beta type (P05771). Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription r….

Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase has been reported to be involved in many different cellular functions, such as B cell activation, apoptosis induction, endothelial cell proliferation, and intestinal sugar absorption. Studies in mice also suggest that this kinase may also regulate neuronal functions and correlate fear-induced conflict behavior after stress. Alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 5579 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 81 total — 1 pathogenic
• Druggable target: yes — 28 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types
• MANE Select transcript: NM_002738

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9395
Approved symbol	PRKCB
Name	protein kinase C beta
Location	16p12.2-p12.1
Locus type	gene with protein product
Status	Approved
Aliases	PKCβ
Ensembl gene	ENSG00000166501
Ensembl biotype	protein_coding
OMIM	176970
Entrez	5579

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000321728, ENST00000463752, ENST00000466124, ENST00000472066, ENST00000482000, ENST00000486868, ENST00000487674, ENST00000498058, ENST00000498739, ENST00000643927, ENST00000645517, ENST00000647422, ENST00000867666, ENST00000914401, ENST00000965655, ENST00000965656, ENST00000965657, ENST00000965658, ENST00000965659

RefSeq mRNA: 2 — MANE Select: NM_002738 NM_002738, NM_212535

CCDS: CCDS10618, CCDS10619

Canonical transcript exons

ENST00000643927 — 17 exons

Exon	Start	End
ENSE00001103616	24172270	24172361
ENSE00001103624	24174518	24174580
ENSE00001122545	24112973	24113069
ENSE00001242743	24191090	24191230
ENSE00001242785	24123835	24123981
ENSE00001242819	24032136	24032247
ENSE00001301256	24214658	24220611
ENSE00001400169	23835983	23836348
ENSE00001678439	23837375	23837406
ENSE00001699103	23988508	23988590
ENSE00001772524	24154684	24154857
ENSE00003463142	24094163	24094297
ENSE00003545547	24092791	24092947
ENSE00003552034	24035419	24035547
ENSE00003612107	24185460	24185567
ENSE00003633639	24185111	24185191
ENSE00003686275	24180790	24180928

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 99.27.

FANTOM5 (CAGE): breadth broad, TPM avg 58.3826 / max 2260.9711, expressed in 840 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153180	53.1947	832
153179	1.3590	471
153182	0.7616	167
153181	0.7269	174
153196	0.6659	117
153207	0.4033	93
153178	0.2944	72
153208	0.2362	58
153206	0.2186	68
153197	0.1261	67

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.27	gold quality
orbitofrontal cortex	UBERON:0004167	99.26	gold quality
frontal pole	UBERON:0002795	99.12	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.97	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.95	gold quality
superior frontal gyrus	UBERON:0002661	98.86	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.70	gold quality
parietal lobe	UBERON:0001872	98.67	gold quality
CA1 field of hippocampus	UBERON:0003881	98.53	gold quality
postcentral gyrus	UBERON:0002581	98.48	gold quality
lateral globus pallidus	UBERON:0002476	98.44	gold quality
occipital lobe	UBERON:0002021	98.26	gold quality
middle frontal gyrus	UBERON:0002702	98.05	gold quality
primary visual cortex	UBERON:0002436	97.96	gold quality
prefrontal cortex	UBERON:0000451	97.48	gold quality
endothelial cell	CL:0000115	97.37	gold quality
pons	UBERON:0000988	97.35	gold quality
entorhinal cortex	UBERON:0002728	97.33	gold quality
frontal cortex	UBERON:0001870	97.15	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.99	gold quality
blood	UBERON:0000178	96.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.64	gold quality
bone marrow cell	CL:0002092	96.63	gold quality
mononuclear cell	CL:0000842	96.41	gold quality
monocyte	CL:0000576	96.37	gold quality
leukocyte	CL:0000738	96.35	gold quality
neocortex	UBERON:0001950	96.35	gold quality
cerebral cortex	UBERON:0000956	95.75	gold quality
cingulate cortex	UBERON:0003027	95.71	gold quality
anterior cingulate cortex	UBERON:0009835	95.68	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	2550.33
E-HCAD-25	yes	87.05
E-HCAD-35	yes	39.20
E-MTAB-6701	yes	16.28
E-GEOD-137537	yes	14.57
E-HCAD-10	yes	13.51
E-MTAB-8498	yes	11.89
E-CURD-119	yes	5.83
E-MTAB-6678	yes	5.35
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FLI1, MAZ, MITF, NFKB, PROX1, RUNX1, SP1, SP3, STAT3

miRNA regulators (miRDB)

53 targeting PRKCB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929

Literature-anchored findings (GeneRIF, showing 40)

• Investigation of the inhibitory effects of chelerythrine chloride on the translocation of the protein kinase C betaI, betaII, zeta in human neutrophils (PMID:11765038)
• PKC-beta 1 when activated enhances calcium flux and protects the assembly of the F-actin cytoskeleton in intestinal monolayers against oxidants. (PMID:12023512)
• A method that uses liquid chromatography electrospray ionization-mass spectrometry to quantify site-specific protein phosphorylation was used to measure the time-dependent increase of phosphorylation by PRKCB2 at a PKC-preferred site, Ser44. (PMID:12033257)
• PKC beta II expressed in human neutrophils can phosphorylate p47phox and induce both its translocation and NADPH oxidase activation as well as the binding of p47phox to the cytosolic fragment of p22phox. (PMID:12056906)
• The turn motif is a phosphorylation switch that regulates binding of Hsp70. (PMID:12080070)
• REVIEW:Interaction of protein kinase C isozymes with membranes containing anionic phospholipids utilizing fluorescent phorbol esters to probe the properties of the C1 domains (PMID:12093536)
• Nephroprotective actions of the ACE inhibitor lisinopril in experimental diabetes mellitus were associated with and thus could be mediated in part by inhibition of diabetes-induced activation of PKC beta isoenzymes in the renal cortex. (PMID:12435880)
• PKCbeta has a role in in the chemotactic response of human monocytes to MCP-1 (PMID:12724308)
• elevated glucose increases the activity of core 2 GlcNAc-T and adhesion of human leukocytes to retinal capillary endothelial cells, in a dose-dependent manner, through diabetes-activated serine/threonine protein kinase C beta2 dependent phosphorylation (PMID:12765965)
• DNA sequence differences in the promoter of PRKCB1 contribute to diabetic nephropathy susceptibility in type I diabetes mellitus (PMID:12874455)
• data indicate a highly specific function of PKCbeta for regulation of TCR-CD28 induced-signaling, IL-2 gene expression and secretion in Jurkat T cells (PMID:12917261)
• PKCalpha and betaII have roles in the regulation of membrane recycling (PMID:14527960)
• protein kinase Cbeta is a direct, downstream target of RUNX1 (PMID:14561740)
• EGF-mediated protection against oxidant disruption of the intestinal barrier function requires PKC-beta1 activation and NF-kappaB suppression. (PMID:14602581)
• These results suggest that phosphorylation of tyrosinase by PKC-beta induces a complex formation between tyrosinase and TRP-1. (PMID:14623273)
• PKCbetaII induces cell invasion through a Ras/Mek-, PKC iota/Rac 1-dependent signaling pathway (PMID:15037605)
• phospholipase D causes translocation of protein kinase C (PKC)betaII but not PKCbetaI to a juxtanuclear subset of recycling endosomes (PMID:15067001)
• RACK-I anchors activated PKC-beta on the melanosome membrane, allowing PKC-beta to phosphorylate tyrosinase (PMID:15252133)
• Protein kinase CbetaII regulates its own expression in rat intestinal epithelial cells and the colonic epithelium in vivo. (PMID:15322124)
• PKC-MAPK pathway mRNAs plays an important role in the development and/or progression of early tissue damage in diabetic nephropathy (PMID:15327405)
• results showed that PKC beta(II) and delta isozymes are essential for the activation of IL-10 production in human monocytes following stimulation by HIV-1 Tat protein (PMID:15488737)
• We analyzed the dependence of the expression of some selected protein kinase C isoenzymes on the availability and/or action of androgens. (PMID:15499829)
• juxtanuclear translocation of protein kinase C betaII is selectively inhibited by a negative feedback mechanism involving ceramide formed from the salvage pathway (PMID:15546881)
• Chemotaxis to PDGF-BB in 25 mmol/L glucose is PKCbetaII-dependent and requires activation of both the PI3K and MAPK pathways. (PMID:15591231)
• PKCbetaII is regulated by PI 3-kinase in HT29 cells (PMID:15647851)
• the level of Smad6s can alter the level of TGF-beta and the subsequent induction of PAI-1 via a FoxD1 transcription site (PMID:15716278)
• This evidence supports that the Hal gene is turned on by glucocorticoids and by glucagon either via PKC or PKA, but prefers the PKA pathway. (PMID:15741241)
• Inhibition of protein phosphatase 2A increased phosphorylation at Ser660 that determines calcium sensitivity and activity of protein kinase c betaII isoform (PMID:15880462)
• Regulation of protein kinase C betaII expression and signaling play critical roles in mediating progenitor to dendritic cell differentiation (PMID:15917249)
• PRKCB1 gene on chromosome 16p may be involved in the etiology of autism. (PMID:16027742)
• The data do not support a strong association between single nucleotide polymorphism of PRKCB and spina bifida risk. (PMID:16080189)
• Furthermore, curcumin strongly repressed the PMA-induced phosphorylation of ERK, JNK, and p38 MAP kinase, which were dependent on the PKC pathway (PMID:16102725)
• Acrosomal exocytosis is regulated through the PKC-mediated phosphorylation of conserved threonines in the polybasic regions of synaptotagmin VI. (PMID:16111671)
• Data show that activity of protein kinase B in hormone-dependent mammary tumors was significantly higher than in tumor tissue from patients with negative receptor status. (PMID:16224561)
• A novel mechanism by which ROS can initiate cell death through the activation of PKC-betaI is reported. (PMID:16236825)
• Protein kinase C can inactivate TRPC3 indirectly by activating protein kinase G, and directly by phosphorylation on Ser-712. (PMID:16331690)
• Protein kinase Calpha, betaI, and betaII isozymes regulate cytokine production in mast cells through MEKK2/ERK5-dependent and -independent pathways. (PMID:16430878)
• Subcellular localization of protein kinase C (PKC)-beta, CD81, and LFA-1 was determined in T lymphocytes. (PMID:16472601)
• increased expression of PKC-alpha and -betaI leads to increased total classical PKC kinase activity; increased activity of the isoenzymes plays a role in accelerated growth of TCC. In carcinoma tissue, PKC expression and activity are under strict control. (PMID:16517978)
• study indicates that PRKCB1 is a predictor for worsening of kidney disease in Japanese subjects with type 2 diabetes (PMID:16567829)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkcba	ENSDARG00000008723
danio_rerio	prkcbb	ENSDARG00000022254
mus_musculus	Prkcb	ENSMUSG00000052889
rattus_norvegicus	Prkcb	ENSRNOG00000012061
drosophila_melanogaster	Pkc53E	FBGN0003091
drosophila_melanogaster	inaC	FBGN0004784
drosophila_melanogaster	Pkn	FBGN0020621
drosophila_melanogaster	Pkcdelta	FBGN0287828
caenorhabditis_elegans		WBGENE00004033
caenorhabditis_elegans		WBGENE00006599
caenorhabditis_elegans		WBGENE00009793

Paralogs (9): PRKCH (ENSG00000027075), PKN2 (ENSG00000065243), PRKCZ (ENSG00000067606), PKN1 (ENSG00000123143), PRKCG (ENSG00000126583), PRKCA (ENSG00000154229), PKN3 (ENSG00000160447), PRKCI (ENSG00000163558), PRKCE (ENSG00000171132)

Protein

Protein identifiers

Protein kinase C beta type — P05771 (reviewed: P05771)

All UniProt accessions (4): P05771, H3BV73, I3L148, I3L1Z0

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at ‘Ser-559’, ‘Ser-644’ and ‘Ser-652’. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at ‘Ser-180’, which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates ‘Ser-36’ of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of ‘Thr-6’ of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 ‘Lys-4’ (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4. Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking. Acts as an activator of ferroptosis by mediating phosphorylation and activation of ACSL4. Also stimulates ferroptosis propagation by catalyzing phosphorylation of FOXK1, thereby promoting LGALS13 secretion.

Subunit / interactions. Interacts with PDPK1/PDK1. Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and AR.

Subcellular location. Cytoplasm. Nucleus. Membrane.

Post-translational modifications. Phosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Autophosphorylation on other sites i.e. in the N-terminal and hinge regions have no effect on enzyme activity. Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade.

Activity regulation. Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615).

Cofactor. Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P05771-1	Beta-I, PRKCB1	yes
P05771-2	Beta-II, PRKCB2

RefSeq proteins (2): NP_002729, NP_997700 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR014375	Protein_kinase_C_a/b/g	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR020454	DAG/PE-bd	Domain
IPR034664	cPKC-beta	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF00069, PF00130, PF00168, PF00433

Enzyme classification (BRENDA):

• EC 2.7.11.13 — protein kinase C (BRENDA: 25 organisms, 203 substrates, 258 inhibitors, 20 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FKKQGSFAKKK	0.0166–0.0599	10
ATP	0.0001–0.0828	4
N6-PHENYL-ATP	0.0124	1
S6-(229-239) PEPTIDE	0.0036	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (73 total): modified residue 17, binding site 16, helix 15, strand 8, domain 3, sequence variant 3, zinc finger region 2, region of interest 2, initiator methionine 1, chain 1, active site 1, splice variant 1, sequence conflict 1, turn 1, compositionally biased region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
9C5F	X-RAY DIFFRACTION	2.41
2I0E	X-RAY DIFFRACTION	2.6
8SE3	X-RAY DIFFRACTION	2.6
8SE4	X-RAY DIFFRACTION	2.68
8SE2	X-RAY DIFFRACTION	2.95
8SE1	X-RAY DIFFRACTION	3.32
9S9T	X-RAY DIFFRACTION	3.42
8SG2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05771-F1	85.95	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 466 (proton acceptor)

Ligand- & substrate-binding residues (16): 186; 187; 187; 193; 246; 246; 247; 248; 248; 248; 251; 252 …

Post-translational modifications (17): 2, 11, 16, 17, 206, 250, 311, 314, 324, 500, 504, 635, 642, 661, 662, 641, 660

Function

Pathways and Gene Ontology

Reactome pathways

42 pathways

ID	Pathway
R-HSA-114516	Disinhibition of SNARE formation
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-416993	Trafficking of GluR2-containing AMPA receptors
R-HSA-418597	G alpha (z) signalling events
R-HSA-4419969	Depolymerization of the Nuclear Lamina
R-HSA-5099900	WNT5A-dependent internalization of FZD4
R-HSA-5218921	VEGFR2 mediated cell proliferation
R-HSA-5668599	RHO GTPases Activate NADPH Oxidases
R-HSA-76005	Response to elevated platelet cytosolic Ca2+
R-HSA-8939246	RUNX1 regulates transcription of genes involved in differentiation of myeloid cells
R-HSA-109582	Hemostasis
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1168372	Downstream signaling events of B Cell Receptor (BCR)
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-168256	Immune System
R-HSA-194138	Signaling by VEGF
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-195721	Signaling by WNT
R-HSA-212436	Generic Transcription Pathway
R-HSA-2980766	Nuclear Envelope Breakdown
R-HSA-372790	Signaling by GPCR
R-HSA-3858494	Beta-catenin independent WNT signaling
R-HSA-388396	GPCR downstream signalling
R-HSA-399719	Trafficking of AMPA receptors
R-HSA-399721	Glutamate binding, activation of AMPA receptors and synaptic plasticity

MSigDB gene sets: 681 (showing top): RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, BENPORATH_ES_WITH_H3K27ME3, BIOCARTA_EDG1_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_B_CELL_ACTIVATION, GOBP_MEMBRANE_DISASSEMBLY, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, HOFMANN_CELL_LYMPHOMA_UP, KEGG_MAPK_SIGNALING_PATHWAY

GO Biological Process (30): adaptive immune response (GO:0002250), regulation of transcription by RNA polymerase II (GO:0006357), protein phosphorylation (GO:0006468), calcium ion transport (GO:0006816), intracellular calcium ion homeostasis (GO:0006874), apoptotic process (GO:0006915), mitotic nuclear membrane disassembly (GO:0007077), signal transduction (GO:0007165), phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway (GO:0007207), regulation of D-glucose transmembrane transport (GO:0010827), negative regulation of D-glucose transmembrane transport (GO:0010829), positive regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030949), positive regulation of insulin secretion (GO:0032024), intracellular signal transduction (GO:0035556), B cell activation (GO:0042113), lipoprotein transport (GO:0042953), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of angiogenesis (GO:0045766), negative regulation of insulin receptor signaling pathway (GO:0046627), B cell receptor signaling pathway (GO:0050853), protein kinase C signaling (GO:0070528), cellular response to carbohydrate stimulus (GO:0071322), presynaptic modulation of chemical synaptic transmission (GO:0099171), positive regulation of ferroptosis (GO:0160020), regulation of synaptic vesicle exocytosis (GO:2000300), immune system process (GO:0002376), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), positive regulation of DNA-templated transcription (GO:0045893), regulation of transport (GO:0051049)

GO Molecular Function (19): chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), calcium,diacylglycerol-dependent serine/threonine kinase activity (GO:0004698), protein kinase C binding (GO:0005080), calcium channel regulator activity (GO:0005246), ATP binding (GO:0005524), zinc ion binding (GO:0008270), histone H3T6 kinase activity (GO:0035403), histone binding (GO:0042393), nuclear androgen receptor binding (GO:0050681), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), spectrin (GO:0008091), calyx of Held (GO:0044305), extracellular exosome (GO:0070062), presynaptic cytosol (GO:0099523), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Downstream signaling events of B Cell Receptor (BCR)	1
Trafficking of AMPA receptors	1
GPCR downstream signalling	1
Nuclear Envelope Breakdown	1
PCP/CE pathway	1
VEGFA-VEGFR2 Pathway	1
RHO GTPase Effectors	1
Platelet activation, signaling and aggregation	1
Transcriptional regulation by RUNX1	1
Transmission across Chemical Synapses	1
Neuronal System	1
Signaling by the B Cell Receptor (BCR)	1
Immune System	1
Signaling by Receptor Tyrosine Kinases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
D-glucose transmembrane transport	2
intracellular anatomical structure	2
binding	2
protein kinase activity	2
protein serine/threonine kinase activity	2
immune response	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
phosphorylation	1
protein modification process	1
metal ion transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
mitotic cell cycle	1
nuclear membrane disassembly	1
mitotic cell cycle process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
G protein-coupled acetylcholine receptor signaling pathway	1
regulation of transmembrane transport	1
regulation of D-glucose transmembrane transport	1
negative regulation of transmembrane transport	1
positive regulation of signal transduction	1
regulation of vascular endothelial growth factor receptor signaling pathway	1
vascular endothelial growth factor receptor signaling pathway	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
signal transduction	1
lymphocyte activation	1
protein transport	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

53 interactions, top by confidence:

A	B	Type	Score
PRKCB	SHCBP1	psi-mi:“MI:0915”(physical association)	0.560
AKT1	PRKCB	psi-mi:“MI:0915”(physical association)	0.550
PRKCA	PRKCB	psi-mi:“MI:0914”(association)	0.530
PRKCD	PRKCB	psi-mi:“MI:0914”(association)	0.530
PRKCA	DUSP11	psi-mi:“MI:0914”(association)	0.530
TINF2	PRKCB	psi-mi:“MI:0915”(physical association)	0.510
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
PRL1	PRKCB	psi-mi:“MI:0407”(direct interaction)	0.440
Glrb	PRKCB	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
HSP90AB1	PRKCB	psi-mi:“MI:0915”(physical association)	0.400
TERF1	PRKCB	psi-mi:“MI:0915”(physical association)	0.370
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AHRR	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
	GAK	psi-mi:“MI:0914”(association)	0.350
PRKAR1A	RBFOX3	psi-mi:“MI:0914”(association)	0.350
SH3GL3	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
PRKCB	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
PRKAR1A	ADAM10	psi-mi:“MI:0914”(association)	0.350
SH3GL3	RBFOX3	psi-mi:“MI:0914”(association)	0.350
PRKCB	CHEK1	psi-mi:“MI:0914”(association)	0.350
PRKCB	PRKCG	psi-mi:“MI:0914”(association)	0.350
COQ8B	DNAJB6	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
MBD4	A2ML1	psi-mi:“MI:0914”(association)	0.350
RDH14	PRKCB	psi-mi:“MI:0914”(association)	0.350

BioGRID (256): EP300 (Biochemical Activity), SHCBP1 (Affinity Capture-MS), DAB2 (Biochemical Activity), PRKCB (Two-hybrid), IKBKB (Co-localization), CHUK (Co-localization), GSK3B (Co-localization), ARRB2 (Affinity Capture-Western), PRKCB (Affinity Capture-Western), PRKCB (Affinity Capture-Western), PRKCB (Affinity Capture-MS), AKT1 (Biochemical Activity), PRKCB (Biochemical Activity), PRKCB (Reconstituted Complex), PRKCB (Affinity Capture-Western)

ESM2 similar proteins: A0A075F932, A8KBH6, F1LM93, K8FE10, O08625, O08835, P04409, P05126, P05130, P05696, P05771, P05772, P10102, P13217, P17252, P20444, P21521, P21579, P21707, P24505, P24506, P24507, P25455, P29101, P34693, P40749, P41823, P46096, P46097, P47191, P47861, P48018, P50232, P68403, P68404, P70169, P70610, P90980, Q14184, Q5FWL4

Diamond homologs: A0JJX5, A1CQG2, A1ZBD6, A2QQ28, A3KGK3, A4IFJ5, A6QQP7, A8KBH6, B1WAZ6, B8N7E5, G0S9J5, O14065, O14795, O43581, O75131, O75923, O94812, P04409, P05126, P05128, P05129, P05696, P05771, P05772, P0C869, P0C871, P10102, P10829, P13677, P17252, P20444, P21521, P27715, P29101, P41823, P41885, P46097, P46935, P49147, P63318

SIGNOR signaling

140 interactions.

A	Effect	B	Mechanism
PRKCB	down-regulates	GSK3A	phosphorylation
PDPK1	up-regulates	PRKCB	phosphorylation
PRKCB	up-regulates	CHAT	phosphorylation
PRKCB	down-regulates	TNNI3	phosphorylation
PRKCB	“up-regulates activity”	PRKCB	phosphorylation
PRKCB	up-regulates	PRKCB	phosphorylation
PRKCB	down-regulates	C5AR1	phosphorylation
BLVRA	up-regulates	PRKCB	phosphorylation
PRKCB	down-regulates	ORAI1	phosphorylation
PRKCB	“up-regulates activity”	ILF3	phosphorylation
PRKCB	down-regulates	IBTK	phosphorylation
“bisindolylmaleimide i”	down-regulates	PRKCB	“chemical inhibition”
3-(1-methyl-3-indolyl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-3-indolyl]pyrrole-2,5-dione	down-regulates	PRKCB	“chemical inhibition”
DVL1P1	up-regulates	PRKCB	binding
PRKCB	up-regulates	ANXA1	phosphorylation
PHLPP2	“down-regulates quantity”	PRKCB	dephosphorylation
PHLPP1	“down-regulates quantity”	PRKCB	dephosphorylation
1,2-diacyl-sn-glycerol	“up-regulates activity”	PRKCB	binding
PHLPP1	“down-regulates quantity by destabilization”	PRKCB	dephosphorylation
PHLPP2	“down-regulates quantity by destabilization”	PRKCB	dephosphorylation
PRKCB	unknown	LMNB1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Intracellular signaling by second messengers	5	12.7×	1e-03
Metabolism of RNA	7	8.1×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-serine phosphorylation	5	53.9×	2e-05
protein phosphorylation	7	10.3×	1e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — DLBCLNOS, HNSC, PRAD, STAD.

Clinical variants and AI predictions

ClinVar

81 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	43
Likely benign	7
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
224499	NM_002738.7(PRKCB):c.275G>T (p.Gly92Val)	Pathogenic

SpliceAI

3706 predictions. Top by Δscore:

Variant	Effect	Δscore
16:23952911:TTTAG:T	donor_gain	1.0000
16:23988588:GAT:G	donor_gain	1.0000
16:23988591:G:GG	donor_gain	1.0000
16:24032127:T:TA	acceptor_gain	1.0000
16:24032128:G:A	acceptor_gain	1.0000
16:24032243:TGACA:T	donor_gain	1.0000
16:24032244:GACA:G	donor_gain	1.0000
16:24032244:GACAG:G	donor_gain	1.0000
16:24032246:CA:C	donor_gain	1.0000
16:24032248:G:GG	donor_gain	1.0000
16:24035408:T:TA	acceptor_gain	1.0000
16:24035416:C:G	acceptor_gain	1.0000
16:24035416:CA:C	acceptor_loss	1.0000
16:24035417:A:AG	acceptor_gain	1.0000
16:24035417:AGC:A	acceptor_loss	1.0000
16:24035417:AGCCT:A	acceptor_gain	1.0000
16:24035418:G:GC	acceptor_gain	1.0000
16:24035418:GC:G	acceptor_gain	1.0000
16:24035418:GCC:G	acceptor_gain	1.0000
16:24035418:GCCT:G	acceptor_gain	1.0000
16:24035418:GCCTG:G	acceptor_gain	1.0000
16:24035529:G:T	donor_gain	1.0000
16:24035545:TCGG:T	donor_loss	1.0000
16:24035546:CGG:C	donor_loss	1.0000
16:24035548:G:GA	donor_loss	1.0000
16:24035548:G:GG	donor_gain	1.0000
16:24092786:TTCA:T	acceptor_loss	1.0000
16:24092788:CAG:C	acceptor_loss	1.0000
16:24092789:A:AG	acceptor_gain	1.0000
16:24092789:A:C	acceptor_loss	1.0000

AlphaMissense

4527 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:23836284:C:G	H37D	1.000
16:23836286:C:A	H37Q	1.000
16:23836286:C:G	H37Q	1.000
16:23836290:T:C	F39L	1.000
16:23836291:T:C	F39S	1.000
16:23836291:T:G	F39C	1.000
16:23836292:C:A	F39L	1.000
16:23836292:C:G	F39L	1.000
16:23836320:T:C	F49L	1.000
16:23836322:C:A	F49L	1.000
16:23836322:C:G	F49L	1.000
16:23836323:T:A	C50S	1.000
16:23836323:T:C	C50R	1.000
16:23836324:G:A	C50Y	1.000
16:23836324:G:C	C50S	1.000
16:23836324:G:T	C50F	1.000
16:23836325:C:G	C50W	1.000
16:23836329:C:G	H52D	1.000
16:23836332:T:A	C53S	1.000
16:23836332:T:C	C53R	1.000
16:23836333:G:A	C53Y	1.000
16:23836333:G:C	C53S	1.000
16:23836333:G:T	C53F	1.000
16:23836334:C:G	C53W	1.000
16:23836341:T:C	F56L	1.000
16:23836342:T:C	F56S	1.000
16:23836343:C:A	F56L	1.000
16:23836343:C:G	F56L	1.000
16:23836345:T:A	I57N	1.000
16:23836347:T:A	W58R	1.000

dbSNP variants (sampled 300 via entrez): RS1000003251 (16:23876894 C>T), RS1000004113 (16:23897374 A>G), RS1000007541 (16:24171785 G>T), RS1000027896 (16:24212539 C>T), RS1000035867 (16:24057757 A>G), RS1000036163 (16:24111396 G>A,C), RS1000037082 (16:24171478 A>G), RS1000042000 (16:24150864 G>A), RS1000042526 (16:24062687 A>G,T), RS1000051516 (16:23917207 T>C,G), RS1000051700 (16:24212930 T>A), RS1000060612 (16:23856063 A>C), RS1000071044 (16:24206775 T>A,G), RS1000075704 (16:23862493 C>A,T), RS1000076987 (16:24082140 T>G)

Disease associations

OMIM: gene MIM:176970 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST001454_14	Rheumatoid arthritis	4.000000e-06
GCST001725_51	Inflammatory bowel disease	1.000000e-09
GCST002936_28	Cadmium levels	1.000000e-06
GCST003265_222	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST003265_223	Post bronchodilator FEV1/FVC ratio in COPD	2.000000e-06
GCST003265_253	Post bronchodilator FEV1/FVC ratio in COPD	1.000000e-06
GCST003265_254	Post bronchodilator FEV1/FVC ratio in COPD	9.000000e-07
GCST003265_255	Post bronchodilator FEV1/FVC ratio in COPD	7.000000e-07
GCST003265_256	Post bronchodilator FEV1/FVC ratio in COPD	6.000000e-07
GCST003265_401	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST003265_402	Post bronchodilator FEV1/FVC ratio in COPD	1.000000e-06
GCST004131_75	Inflammatory bowel disease	2.000000e-07
GCST004133_72	Ulcerative colitis	2.000000e-07
GCST004145_9	Primary biliary cholangitis	4.000000e-09
GCST005537_103	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	3.000000e-09
GCST006585_869	Blood protein levels	2.000000e-06
GCST006914_6	Sleep duration	6.000000e-06
GCST009378_20	Bone mineral content	9.000000e-06
GCST011494_70	Daytime nap	2.000000e-09
GCST011956_149	Systemic lupus erythematosus	1.000000e-12
GCST90002388_164	Lymphocyte count	3.000000e-09
GCST90002388_165	Lymphocyte count	7.000000e-12
GCST90006998_7	Gut microbiota relative abundance (Dorea)	4.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0007621	bone mineral content measurement
EFO:0007828	daytime rest measurement
EFO:0004587	lymphocyte count
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2096620 (PROTEIN FAMILY), CHEMBL3045 (SINGLE PROTEIN), CHEMBL3137267 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

28 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 301,847 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1863513	INGENOL MEBUTATE	4	1,475
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL83	TAMOXIFEN	4	171,635
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL265502	SURAMIN	3	36,848
CHEMBL38380	FASUDIL	3	11,953
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL2107337	ENZASTAURIN HYDROCHLORIDE	3	516
CHEMBL2219422	AFURESERTIB	3	1,467
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2	1,362
CHEMBL28509	EDELFOSINE	2	10,540
CHEMBL3137336	UPROSERTIB	2	1,624
CHEMBL574737	UCN-01	2	2,217
CHEMBL103667	DORAMAPIMOD	2	1,681
CHEMBL1944698	ZOTIRACICLIB	2	2,915
CHEMBL3039513	DECERNOTINIB	2
CHEMBL362558	LY-2090314	2
CHEMBL3982723	DAROVASERTIB	2
CHEMBL495727	AT-9283	2
CHEMBL565612	SOTRASTAURIN	2
CHEMBL3128043	PF-03758309	1
CHEMBL494089	GSK-690693	1
CHEMBL571948	Y-39983	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11649514	Toxicity	3	atenolol	Hyperglycemia
rs9922316	Other	3	dexmedetomidine

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9922316	PRKCB	3	1.50	1	dexmedetomidine
rs11649514	PRKCB	3	2.50	1	atenolol

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Alpha subfamily

Most potent curated ligand interactions (13 total), top 13:

Ligand	Action	Affinity	Parameter
ingenol mebutate	Activation	9.98	pKi
sotrastaurin	Inhibition	8.7	pIC50
PKCbeta inhibitor	Inhibition	8.3	pIC50
ruboxistaurin	Inhibition	8.23	pIC50
Gö 6983	Inhibition	8.15	pIC50
balanol	Inhibition	8.0	pIC50
10-Me-Aplog-1	Activation	7.92	pKi
GF109203X	Inhibition	7.8	pIC50
7-hydroxystaurosporine	Inhibition	7.54	pIC50
enzastaurin	Inhibition	7.52	pIC50
Ro-32-0432	Inhibition	7.52	pIC50
bisindolylmaleimide IV	Inhibition	6.67	pIC50
CGP53353	Inhibition	6.4	pIC50

Binding affinities (BindingDB)

338 measured of 392 human assays (394 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4442196	IC50	0.09 nM
[(1S,4S,5S,6R,9S,10S,12R)-5,6-dihydroxy-7-(hydroxymethyl)-3,11,11-trimethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] 1-methylcyclohexane-1-carboxylate	EC50	0.1 nM	US-9409931: 3-O-acyl-ingenol analogues
CHEMBL3741746	IC50	0.13 nM
CHEMBL4528495	IC50	0.15 nM
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
[(4R,5R,6S,9S,10S,12R,14R)-6-hydroxy-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] 1-methylcyclohexane-1-carboxylate	EC50	0.2 nM	US-9409931: 3-O-acyl-ingenol analogues
CHEMBL4435580	IC50	0.22 nM
Butyric acid (1aS,1bS,4aS,7aS,8R,9S,9aR)-9-butyryloxy-4a,7b-dihydroxy-3-((R)-hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1,1a,1b,4,4a,5,7a,7b,8,9-decahydro-cyclopropa[3,4]benzo[1,2-e]azulen-9a-yl ester	KD	0.28 nM
CHEMBL4587471	IC50	0.36 nM
Bryostatin	KD	0.44 nM
CHEMBL4575056	EC50	0.6 nM
bryostatin 1	KD	0.73 nM
[(1S,4S,5R,9S,10S,12R,14R)-5-hydroxy-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] 1-methylcyclohexane-1-carboxylate	EC50	0.8 nM	US-9409931: 3-O-acyl-ingenol analogues
maleimide derivative, 12	IC50	0.9 nM
[3-[(2-ethoxy-5-fluoropyrimidin-4-yl)amino]-6,6-dimethyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazol-5-yl]-[(2S,5R)-2,4,5-trimethylpiperazin-1-yl]methanone	KI	1.12 nM	US-11220518: Substituted n-pyrimidin-4-yl-3-amino-pyrrolo[3,4-c]pyrazoles as protein kinase C inhibitors
[3-[(3-fluoro-6-methyl-2-pyridinyl)amino]-6,6-dimethyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazol-5-yl]-[(2S)-2,4,5,5-tetramethylpiperazin-1-yl]methanone	KI	1.17 nM	US-11220518: Substituted n-pyrimidin-4-yl-3-amino-pyrrolo[3,4-c]pyrazoles as protein kinase C inhibitors
N-[5-[(2S,5R)-2,5-dimethyl-4-(oxan-4-yl)piperazine-1-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]pyridine-2-carboxamide	KI	1.7 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
[3-[(5-fluoro-2-propylpyrimidin-4-yl)amino]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-5-yl]-[(2S)-2,4,5,5-tetramethylpiperazin-1-yl]methanone	KI	1.73 nM	US-11220518: Substituted n-pyrimidin-4-yl-3-amino-pyrrolo[3,4-c]pyrazoles as protein kinase C inhibitors
N-[5-[(2S,5R)-2,5-dimethyl-4-(oxan-4-ylmethyl)piperazine-1-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]pyridine-2-carboxamide	KI	1.9 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
AEB071	IC50	2.1 nM
[3-[[5-fluoro-2-(methoxymethyl)pyrimidin-4-yl]amino]-6,6-dimethyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazol-5-yl]-[(2S)-2,4,5,5-tetramethylpiperazin-1-yl]methanone	KI	2.1 nM	US-11220518: Substituted n-pyrimidin-4-yl-3-amino-pyrrolo[3,4-c]pyrazoles as protein kinase C inhibitors
maleimide derivative, 10	IC50	2.2 nM
2-[1-(3-dimethylaminopropyl)-indol-3-yl]-3-(indol-3-yl)maleimide	IC50	2.3 nM
[3-[(3-fluoro-6-methyl-2-pyridinyl)amino]-6,6-dimethyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazol-5-yl]-[(2S,5R)-2,4,5-trimethylpiperazin-1-yl]methanone	KI	2.63 nM	US-11220518: Substituted n-pyrimidin-4-yl-3-amino-pyrrolo[3,4-c]pyrazoles as protein kinase C inhibitors
N-[5-[(8S)-6,8-dimethyl-6,9-diazaspiro[4.5]decane-9-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]pyridine-2-carboxamide	KI	3.05 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[5-[(2S,5R)-2,5-dimethyl-4-(oxan-4-ylmethyl)piperazine-1-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-5-(trifluoromethyl)pyridine-2-carboxamide	KI	4.17 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
[3-[(2-ethyl-5-fluoropyrimidin-4-yl)amino]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-5-yl]-[(2S)-2,4,5,5-tetramethylpiperazin-1-yl]methanone	KI	5.43 nM	US-11220518: Substituted n-pyrimidin-4-yl-3-amino-pyrrolo[3,4-c]pyrazoles as protein kinase C inhibitors
N-[5-[(3S,8aS)-3-methyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-2-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]isoquinoline-3-carboxamide	KI	5.51 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
[(1S,4R,5S,9S,10S,12R,14R)-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] 1-methylcyclohexane-1-carboxylate	EC50	6 nM	US-9409931: 3-O-acyl-ingenol analogues
N-[5-[(3S,8aS)-3-methyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-2-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-1,6-naphthyridine-2-carboxamide	KI	6.17 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[5-[(3S,8aS)-3-methyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-2-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-5-cyclopropyl-1H-pyrazole-3-carboxamide	KI	6.81 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
maleimide derivative, 11	IC50	7.1 nM
N-[5-[(7S)-5,7-dimethyl-5,8-diazaspiro[3.5]nonane-8-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]pyridine-2-carboxamide	KI	8.58 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[5-[(2S,5R)-4-ethyl-2,5-dimethylpiperazine-1-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]pyridine-2-carboxamide	KI	9.11 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[5-[(2S,5R)-5-(2-hydroxyethyl)-2-methyl-4-propylpiperazine-1-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]pyridine-2-carboxamide	KI	9.53 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[5-[(3S,8aS)-3-methyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-2-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-4,5-dichloro-1,3-thiazole-2-carboxamide	KI	10.4 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[5-[(3S,8aS)-3-methyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-2-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-3-tert-butyl-1-methylpyrazole-5-carboxamide	KI	10.6 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[6,6-dimethyl-5-[(2S)-2-methyl-4-(oxan-4-ylmethyl)piperazine-1-carbonyl]-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-4-fluorobenzamide;methane	KI	11.2 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
5-chloro-N-[6,6-dimethyl-5-[(2S)-2-methyl-4-(oxan-4-ylmethyl)piperazine-1-carbonyl]-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]pyridine-2-carboxamide;methane	KI	11.9 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[5-[(2S,5R)-2,5-dimethyl-4-(oxan-4-yl)piperazine-1-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-5-methylpyridine-2-carboxamide	KI	12.2 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[5-[(3S,8aS)-3-methyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-2-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]quinoxaline-2-carboxamide	KI	12.5 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[6,6-dimethyl-5-[(2S)-2-methyl-4-(oxan-4-ylmethyl)piperazine-1-carbonyl]-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-5-fluoropyridine-2-carboxamide;methane	KI	12.8 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[6,6-dimethyl-5-[(2S)-2-methyl-4-(oxan-4-ylmethyl)piperazine-1-carbonyl]-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-2-methyl-1,3-thiazole-4-carboxamide;methane	KI	12.8 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
[3-[[5-fluoro-2-(3-methoxypropoxy)pyrimidin-4-yl]amino]-6,6-dimethyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazol-5-yl]-[(2S)-2,4,5,5-tetramethylpiperazin-1-yl]methanone	KI	12.8 nM	US-11220518: Substituted n-pyrimidin-4-yl-3-amino-pyrrolo[3,4-c]pyrazoles as protein kinase C inhibitors
N-[5-[(6R,8aS)-6-methyl-1,2,3,5,6,7,8,8a-octahydroindolizine-7-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-2-bromo-1,3-thiazole-4-carboxamide	KI	12.9 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
[3-[(2-ethoxypyrimidin-4-yl)amino]-6,6-dimethyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazol-5-yl]-[(2S,5R)-2,4,5-trimethylpiperazin-1-yl]methanone	KI	13.1 nM	US-11220518: Substituted n-pyrimidin-4-yl-3-amino-pyrrolo[3,4-c]pyrazoles as protein kinase C inhibitors
N-[5-[(2S)-4-(cyclopropylmethyl)-2-methylpiperazine-1-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]pyridine-2-carboxamide;methane	KI	13.3 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[5-[(2S)-4-butyl-2-methylpiperazine-1-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]pyridine-2-carboxamide;methane	KI	13.3 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives
N-[5-[(3S,8aS)-3-methyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-2-carbonyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-3,4-dichlorobenzamide	KI	13.9 nM	US-8999981: 3-amido-pyrrolo[3,4-C]pyrazole-5(1H, 4H,6H) carbaldehyde derivatives

ChEMBL bioactivities

1326 potent at pChembl≥5 of 1440 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	STAUROSPORINE
10.05	IC50	0.09	nM	CHEMBL4442196
10.00	EC50	0.1	nM	CHEMBL3926213
9.89	IC50	0.13	nM	CHEMBL3741746
9.85	IC50	0.14	nM	CHEMBL4575056
9.82	IC50	0.15	nM	CHEMBL4528495
9.78	Ki	0.165	nM	CHEMBL5764715
9.77	Ki	0.17	nM	DEBROMOAPLYSIATOXIN
9.77	IC50	0.17	nM	CHEMBL4538431
9.74	IC50	0.18	nM	CHEMBL4443190
9.74	Ki	0.181	nM	CHEMBL5992520
9.72	EC50	0.19	nM	CHEMBL3741746
9.72	Kd	0.19	nM	CHEMBL337834
9.70	IC50	0.2	nM	CHEMBL2151411
9.70	EC50	0.2	nM	CHEMBL4113544
9.66	IC50	0.22	nM	CHEMBL4435580
9.44	IC50	0.36	nM	CHEMBL4587471
9.43	Ki	0.376	nM	CHEMBL6057218
9.40	Ki	0.4	nM	CHEMBL285801
9.35	Ki	0.45	nM	APLYSIATOXIN
9.30	Ki	0.5	nM	CHEMBL4077967
9.26	EC50	0.55	nM	CHEMBL4587471
9.22	IC50	0.6	nM	CHEMBL1996510
9.22	EC50	0.6	nM	CHEMBL4575056
9.22	IC50	0.6	nM	STAUROSPORINE
9.19	IC50	0.64	nM	SOTRASTAURIN
9.17	Ki	0.683	nM	CHEMBL5912753
9.15	IC50	0.7	nM	CHEMBL4102228
9.10	EC50	0.8	nM	CHEMBL4115540
9.04	Ki	0.912	nM	CHEMBL6041594
9.00	IC50	1	nM	STAUROSPORINE
9.00	Ki	1.01	nM	CHEMBL5988431
8.95	Ki	1.12	nM	CHEMBL6049355
8.93	Ki	1.17	nM	CHEMBL5769039
8.92	IC50	1.2	nM	CHEMBL2153750
8.89	Kd	1.3	nM	CHEMBL27768
8.88	Kd	1.31	nM	CHEMBL27768
8.87	Kd	1.34	nM	CHEMBL27768
8.85	IC50	1.4	nM	CHEMBL2151415
8.85	IC50	1.413	nM	CHEMBL2236794
8.85	IC50	1.4	nM	CHEMBL2236794
8.85	IC50	1.4	nM	CHEMBL4072879
8.85	Ki	1.42	nM	CHEMBL337834
8.84	IC50	1.44	nM	STAUROSPORINE
8.82	Ki	1.5	nM	DEMETHOXYDEBROMOAPLYSIATOXIN
8.80	IC50	1.6	nM	GF-109203
8.79	Ki	1.64	nM	CHEMBL5902043
8.77	Ki	1.7	nM	CHEMBL3662851
8.77	IC50	1.7	nM	CHEMBL291126
8.77	Ki	1.71	nM	CHEMBL5924468

PubChem BioAssay actives

743 with measured affinity, of 3213 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-12-benzoyloxy-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-22-acetyloxy-12-benzoyloxy-10,11-dihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] naphthalene-2-carboxylate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,25R)-12-benzoyloxy-10,11-dihydroxy-9-(hydroxymethyl)-13,15-dimethyl-22-oxo-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	165147: Inhibition Protein kinase C (PKC)	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] 4-nitrobenzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-12-benzoyloxy-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-propan-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] 4-methoxybenzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
N-[(2S,5S)-5-(hydroxymethyl)-1-methyl-3-oxo-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-8-yl]-N’-[(2S,5S)-5-(hydroxymethyl)-1-methyl-3-oxo-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-9-yl]tetradecanediamide	163205: Binding affinity for human PKC beta-1	kd	0.0002	uM
3-(7-methyl-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	689999: Inhibition of PKCbeta-1 by scintillation proximity assay	ic50	0.0002	uM
(1S,3R,4S,5S,9R,13S,14R)-13-hydroxy-9-[(1R)-1-hydroxyethyl]-3-[(2S,5S)-5-(3-hydroxyphenyl)-5-methoxypentan-2-yl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	687830: Inhibition of [3H]PDBu binding to PKCbeta C1A domain	ki	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] pyridine-4-carboxylate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0004	uM
(10S,13S)-13-(hydroxymethyl)-9-methyl-5-octyl-10-propan-2-yl-3,9,12-triazatricyclo[6.6.1.04,15]pentadeca-1,4,6,8(15)-tetraen-11-one	163193: Displacement of [3H]- PDBu from recombinant PKC beta expressed in baculovirus	ki	0.0004	uM
(1S,3R,4S,5S,9R,13S,14R)-3-[(2S,5S)-5-(2-bromo-5-hydroxyphenyl)-5-methoxypentan-2-yl]-13-hydroxy-9-[(1R)-1-hydroxyethyl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	517263: Inhibition of [3H]PDBu binding to PKC beta C1A peptide	ki	0.0004	uM
3-[2-chloro-7-[(dimethylamino)methyl]naphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437231: Reversible competitive inhibition of PKCbeta1 (unknown origin)	ki	0.0005	uM
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	1902439: Inhibition of PKCbeta1 (unknown origin) by IMAP kinase assay	ic50	0.0006	uM
3-(1H-indol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	689999: Inhibition of PKCbeta-1 by scintillation proximity assay	ic50	0.0006	uM
3-[2-chloro-7-[(dimethylamino)methyl]naphthalen-1-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0007	uM
3-[6-fluoro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	689999: Inhibition of PKCbeta-1 by scintillation proximity assay	ic50	0.0012	uM
[(1S,2S,6R,10S,11R,13S,14R,15R)-13-butanoyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] butanoate	163363: Binding affinity for Protein kinase C beta C1a domain	kd	0.0013	uM
3-[2-chloro-7-(methylaminomethyl)naphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0014	uM
3-(1-methylindol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	689999: Inhibition of PKCbeta-1 by scintillation proximity assay	ic50	0.0014	uM
(1S,3R,4S,5S,9R,13S,14R)-13-hydroxy-9-[(1R)-1-hydroxyethyl]-3-[(2S)-5-(3-hydroxyphenyl)pentan-2-yl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	768065: Displacement of [3H]PDBu from PKCbeta C1A domain (unknown origin)	ki	0.0015	uM
3-[1-[3-(dimethylamino)propyl]indol-3-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	1799253: Protein Kinase Assays from Article 10.1021/jm901108b: “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.”	ic50	0.0016	uM
(15R,16R,18S)-16-(hydroxymethyl)-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-3,5-dione	155717: In vitro inhibition of protein kinase C (PKC)	ic50	0.0017	uM
[(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] tetradecanoate	220908: Inhibition of [3H]-phorbol 12,13-dibutyrate (PDBu) binding to human recombinant protein kinase C beta	ki	0.0018	uM
3-(1H-indol-3-yl)-4-[3-(4-methylpiperazin-1-yl)naphthalen-1-yl]pyrrole-2,5-dione	1799253: Protein Kinase Assays from Article 10.1021/jm901108b: “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.”	ic50	0.0018	uM
2-[2,6-dihydroxy-4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	1315726: Binding affinity to PKCbeta2 (unknown origin) using Lys-Arg-Thr-Leu-Arg-Arg as substrate after 8 mins in presence of [gamma-32P]ATP by liquid scintillation spectrometry	kd	0.0018	uM
3-(1H-indol-3-yl)-4-[3-(4-methylpiperazin-1-yl)isoquinolin-1-yl]pyrrole-2,5-dione	689999: Inhibition of PKCbeta-1 by scintillation proximity assay	ic50	0.0020	uM
2-[4-[(1R,2R,4R)-4-amino-2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonyl-2,6-dihydroxybenzoyl]-3-hydroxybenzoic acid	163351: Inhibitory concentration against recombinant human Protein kinase C beta 2 isozyme	ic50	0.0020	uM
3-[7-(azetidin-1-ylmethyl)-2-chloronaphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0020	uM
3-(23-methyl-14-oxo-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaen-3-yl)propanenitrile	325569: Inhibition of PKCbeta	ic50	0.0020	uM
3-[3-(4-anilino-2,5-dioxopyrrol-3-yl)indol-1-yl]propyl carbamimidothioate;hydrobromide	241463: Inhibitory concentration against recombinant human Protein kinase C beta 2	ic50	0.0020	uM
3-[3-[2-(dimethylamino)ethoxy]naphthalen-1-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	1799253: Protein Kinase Assays from Article 10.1021/jm901108b: “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.”	ic50	0.0021	uM
[(1R,2R,6S,10S,11R,13S,14R,15R)-13-butanoyloxy-1-hydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] butanoate	163372: Displacement of 3[H]PDBu from Protein kinase C beta C1b domain	ki	0.0022	uM
3-[2-chloro-7-[(propan-2-ylamino)methyl]naphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0029	uM
2-[2,6-dihydroxy-4-[(1R,2R,4S)-2-[(4-hydroxybenzoyl)amino]-4-(hydroxymethyl)cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	163351: Inhibitory concentration against recombinant human Protein kinase C beta 2 isozyme	ic50	0.0030	uM
2-[2,6-dihydroxy-4-[2-[(4-hydroxyphenyl)methyl]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	163340: Evaluated against recombinant human Protein kinase C beta 2	ic50	0.0030	uM
2-[2,6-dihydroxy-4-[(1R,2S)-2-[(4-hydroxyphenyl)methyl]cyclopentyl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	1795485: PKC assay from Article 10.1021/jm960581w: “Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A.”	ic50	0.0030	uM
3-[2-chloro-7-[(2-methoxyethylamino)methyl]naphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0031	uM
3-[7-(aminomethyl)-2-chloronaphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0033	uM
3-[2-chloro-6-[(dimethylamino)methyl]naphthalen-1-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	1437218: Inhibition of PKCbeta1 (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0034	uM
3-(1H-indol-3-yl)-4-[5-methyl-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	689999: Inhibition of PKCbeta-1 by scintillation proximity assay	ic50	0.0038	uM
3-[1-[3-(dimethylamino)propyl]indazol-3-yl]-4-(1-quinolin-3-ylindol-3-yl)pyrrole-2,5-dione	241735: Inhibition of human Protein kinase C beta 2 using [gamma-33P]-ATP	ic50	0.0040	uM
2-[4-[(1R,2R,4S)-4-(aminomethyl)-2-[(4-hydroxybenzoyl)amino]cyclopentyl]oxycarbonyl-2,6-dihydroxybenzoyl]-3-hydroxybenzoic acid	163200: Inhibitory concentration against recombinant human Protein kinase C beta 1 isozyme	ic50	0.0040	uM
[2-(hydroxymethyl)-5-oxo-4-propan-2-ylideneoxolan-2-yl]methyl 4-[2-(4-methylphenyl)ethynyl]benzoate	350005: Displacement of [3H]PDBu form human PKCbeta in presence of phosphatidylserine	ki	0.0041	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione;methanesulfonic acid	163199: Inhibition of Protein kinase C beta 1	ic50	0.0047	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	1397956: Inhibition of DAG-activated human PKCbeta1 after 10 mins in presence of [32P]ATP by beta scintillation counting method	ic50	0.0047	uM
3-[1-[3-(dimethylamino)propyl]indazol-3-yl]-4-(1-naphthalen-2-ylindol-3-yl)pyrrole-2,5-dione	241735: Inhibition of human Protein kinase C beta 2 using [gamma-33P]-ATP	ic50	0.0050	uM
(18S)-18-(methylaminomethyl)-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	163197: Inhibition of Protein kinase C beta 1	ic50	0.0050	uM

CTD chemical–gene interactions

118 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	affects localization, decreases reaction, decreases phosphorylation, increases localization, increases reaction (+6 more)	11
Valproic Acid	affects cotreatment, increases expression, affects expression, affects methylation	9
Tretinoin	increases expression, increases reaction, increases phosphorylation	5
Arsenic Trioxide	increases expression, affects response to substance, increases reaction, decreases expression	4
Resveratrol	increases phosphorylation, affects cotreatment, decreases expression, decreases reaction, increases activity	3
Benzo(a)pyrene	increases expression, decreases expression, decreases methylation, increases methylation	3
Glucose	decreases reaction, increases expression, increases activity, increases phosphorylation	3
mercuric bromide	decreases expression, affects cotreatment	2
Bandrowski’s base	increases expression, affects reaction	2
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Decitabine	decreases reaction, increases expression, affects expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Copper	affects cotreatment, affects binding, decreases expression	2
Deoxycholic Acid	decreases reaction, increases expression, increases activity	2
Metformin	decreases reaction, increases expression, decreases expression	2
Nickel	increases expression	2
Ozone	increases abundance, increases expression, affects expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, affects cotreatment, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
quinone	increases expression	1
methylmercuric chloride	decreases expression	1
naringenin	affects localization, decreases reaction	1
bis(tri-n-butyltin)oxide	increases expression	1

ChEMBL screening assays

973 unique, capped per target: 951 binding, 21 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000235	Binding	Activation of PKC in PMA-stimulated human LNCAP cells assessed as ERK phosphorylation at 1 nM to 10 uM by Western blot relative to PMA	Conformationally constrained analogues of diacylglycerol (DAG). 31. Modulation of the biological properties of diacylgycerol lactones (DAG-lactones) containing rigid-rod acyl groups separated from the core lactone by spacer units of different lengths. — J Med Chem
CHEMBL688555	Functional	Retained protein kinase C activity in the presence of 1.25 uM compound	Synthesis and biological activity of novel quaternary ammonium derivatives of alkylglycerols as potent inhibitors of protein kinase C. — J Med Chem
CHEMBL4424904	ADMET	Inhibition of human N-terminal His6-tagged (2 to end residues) PKCbeta expressed in baculovirus infected Sf21 insect cells using Histone H1 as substrate	Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952. — Bioorg Med Chem Lett

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8N5	Abcam HCT 116 PRKCB KO	Cancer cell line	Male
CVCL_B9AQ	Abcam MCF-7 PRKCB KO	Cancer cell line	Female
CVCL_B9QE	Abcam A-549 PRKCB KO	Cancer cell line	Male
CVCL_D9PL	Ubigene HEK293 PRKCB KO	Transformed cell line	Female
CVCL_E0LV	Ubigene HeLa PRKCB KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.