PRKCE

Summary

PRKCE (protein kinase C epsilon, HGNC:9401) is a protein-coding gene on chromosome 2p21, encoding Protein kinase C epsilon type (Q02156). Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions….

Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the 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 kinase has been shown to be involved in many different cellular functions, such as neuron channel activation, apoptosis, cardioprotection from ischemia, heat shock response, as well as insulin exocytosis. Knockout studies in mice suggest that this kinase is important for lipopolysaccharide (LPS)-mediated signaling in activated macrophages and may also play a role in controlling anxiety-like behavior.

Source: NCBI Gene 5581 — RefSeq curated summary.

At a glance

• GWAS associations: 91
• Clinical variants (ClinVar): 68 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005400

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9401
Approved symbol	PRKCE
Name	protein kinase C epsilon
Location	2p21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171132
Ensembl biotype	protein_coding
OMIM	176975
Entrez	5581

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding_CDS_not_defined, 4 protein_coding

ENST00000306156, ENST00000394874, ENST00000421201, ENST00000462720, ENST00000467135, ENST00000469753, ENST00000472021, ENST00000476675, ENST00000480453, ENST00000480633, ENST00000485176, ENST00000489067, ENST00000494472, ENST00000497602, ENST00000498388, ENST00000872579

RefSeq mRNA: 1 — MANE Select: NM_005400 NM_005400

CCDS: CCDS1824

Canonical transcript exons

ENST00000306156 — 15 exons

Exon	Start	End
ENSE00001169438	46151041	46151229
ENSE00001169459	46007462	46007661
ENSE00001169464	46004542	46004638
ENSE00001169474	45984551	45984680
ENSE00001326267	46184735	46187990
ENSE00001779178	46010344	46010517
ENSE00001829860	45651675	45652448
ENSE00003488235	45980296	45980381
ENSE00003507286	46159606	46159752
ENSE00003509073	46086208	46086362
ENSE00003621522	45976429	45976588
ENSE00003625267	45843000	45843063
ENSE00003632577	45978976	45979010
ENSE00003649344	46001404	46001546
ENSE00003678245	46145093	46145231

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 96.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1985 / max 222.6898, expressed in 1696 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20039	7.4348	1551
20038	3.2826	1182
20051	1.3922	379
202178	0.5233	287
20040	0.3959	163
20052	0.1135	52
202179	0.0441	13
20043	0.0063	3
20047	0.0057	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.63	gold quality
sural nerve	UBERON:0015488	94.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.53	gold quality
parietal lobe	UBERON:0001872	93.96	gold quality
postcentral gyrus	UBERON:0002581	93.57	gold quality
right lung	UBERON:0002167	93.43	gold quality
middle temporal gyrus	UBERON:0002771	93.42	gold quality
cortical plate	UBERON:0005343	93.01	gold quality
sperm	CL:0000019	92.95	gold quality
superior frontal gyrus	UBERON:0002661	91.79	gold quality
entorhinal cortex	UBERON:0002728	91.76	gold quality
pons	UBERON:0000988	91.09	gold quality
prefrontal cortex	UBERON:0000451	91.02	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.24	gold quality
male germ cell	CL:0000015	89.88	gold quality
occipital lobe	UBERON:0002021	89.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.43	gold quality
primary visual cortex	UBERON:0002436	89.38	gold quality
upper lobe of left lung	UBERON:0008952	88.57	gold quality
frontal cortex	UBERON:0001870	88.36	gold quality
left testis	UBERON:0004533	88.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.16	gold quality
upper lobe of lung	UBERON:0008948	88.12	gold quality
right testis	UBERON:0004534	88.10	gold quality
neocortex	UBERON:0001950	87.98	gold quality
cerebellar cortex	UBERON:0002129	87.97	gold quality
cerebral cortex	UBERON:0000956	87.90	gold quality
cerebellar hemisphere	UBERON:0002245	87.90	gold quality
dorsal root ganglion	UBERON:0000044	87.25	gold quality
Ammon’s horn	UBERON:0001954	87.21	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	36.89
E-CURD-119	yes	17.41
E-ANND-3	yes	13.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, BHLHE40, CREB1, EGR1, FOS, JUN, NFKB, PAX5, PPARG, SP1, STAT1, ZHX2

miRNA regulators (miRDB)

210 targeting PRKCE, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817

Literature-anchored findings (GeneRIF, showing 40)

• Isoforms of protein kinase C and their distribution in human adrenal cortex and tumors (PMID:11740573)
• PKCepsilon mediates neurite induction by increased association to the cytoskeleton during neuronal differentiation. (PMID:11809819)
• Switch chimeras, containing the C1B from epsilonPKC in the context of deltaPKC (delta(epsilonC1B)) and vice versa (epsilon(deltaC1B)), were generated and tested for their translocation in response to ceramide and arachidonic acid. (PMID:11877428)
• Direct phosphorylation of capsaicin receptor VR1 by protein kinase Cepsilon and identification of two target serine residues (PMID:11884385)
• The anchoring protein RACK1 links protein kinase Cepsilon to integrin beta chains. (PMID:11934885)
• Protein kinase C epsilon-dependent regulation of cystic fibrosis transmembrane regulator involves binding to a receptor for activated C kinase (RACK1) and RACK1 binding to Na+/H+ exchange regulatory factor. (PMID:11956211)
• The contribution of PKCepsilon kinase activity in controlling the phosphorylation of Thr(566) and Ser(729)of PKCE. (PMID:11964154)
• No thyroid papillary carcinoma, follicular adenoma, or anaplastic carcinoma harbored the PKCalpha 881A>G mutation. (PMID:11994357)
• Critical role of diacylglycerol- and phospholipid-regulated protein kinase C epsilon in induction of low-density lipoprotein receptor transcription in response to depletion of cholesterol. (PMID:11997513)
• 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)
• promotes survival of lung cancer cells by suppressing apoptosis through dysregulation of the mitochondrial caspase pathway (PMID:12121973)
• role in regulating caveolin-1 expression and secretion (PMID:12185081)
• activation inhibited TNF-induced apoptosis in MCF-7 cells (PMID:12198125)
• Protein kinase C-epsilon mediates bradykinin-induced cyclooxygenase-2 expression in human airway smooth muscle cells (PMID:12205039)
• PKCepsilon-mediated inhibition of Cl-/OH- exchange activity in Caco-2 cells (PMID:12372810)
• PKCepsilon as the key isoform responsible for actin disruption in T84 cells (PMID:12372816)
• Protein kinase C epsilon plays a role in lipopolysaccharide-induced IL-12 synthesis in monocyte-derived dendritic cells. (PMID:12385023)
• absence of protein kinase C-epsilon allows increased expression of potassium(V) channels (like Kv3.1b) to occur in pulmonary artery smooth muscle cells, which likely contributes to decreased hypoxic pulmonary vasoconstriction (PMID:12505875)
• selective modulation of novel PKC epsilon may regulate TNF-R1 signaling in intestinal epithelium. (PMID:12505880)
• Il-2 and polysaccharide K increased expression of protein kinase C epsilon. (PMID:12536241)
• The novel varepsilon and eta and atypical zeta, but not the conventional alpha and beta and the novel delta PKCs, may be involved in the signaling pathways involved in thrombin-induced human platelet P-selectin expression (PMID:12783114)
• our data suggest that an association of PKCepsilon with Bax may neutralize apoptotic signals propagated through a mitochondrial death-signaling pathway. (PMID:12970744)
• PKC-epsilon is specifically required in the signaling pathway leading to the induction of hsp90 beta gene in response to heat shock. (PMID:14532285)
• PKC epsilon (epsilon) was recently found to be a critical component of TLR-4 signaling pathway and thereby to play a key role in macrophage and dendritic cell (DC) activation in response to LPS [review] (PMID:14643884)
• PKCdelta and PKCepsilon may offer novel targets for development of cancer preventive or therapeutic agents that selectively inactivate PKCepsilon or stimulate PKCdelta. (PMID:14656938)
• A putative Rac1/Cdc42/PKC-alpha pathway is convergent with the PKC-epsilon/MEK1/2 pathway in terms of the activation of JNK by PMA. (PMID:14709334)
• Induction of neurites by the regulatory domain of PKCE is counteracted by PKC catalytic activity and RhoA GTP-binding protein metabolism. (PMID:14720513)
• intramolecular within epsilon PKC is critical and rate limiting in the process of PKC translocation (PMID:14739299)
• protein kinase Cepsilon has a role in phosphorylation of the activation loop of protein kinase D (PMID:15190080)
• Results suggest that the involvement of protein kinase C alpha in carbachol-induced soluble amyloid precursor protein (sAPPalpha) release is negligible, but PKC epsilon may be important in coupling cholinergic receptors with APP metabolism. (PMID:15233804)
• Use of PKC agonists and isozyme-specific pseudosubstrate peptide antagonists suggested a role for PKCalpha and -epsilon in VEGF-mediated DAF up-regulation, mediating A cytoprotective pathway in ECs. (PMID:15284224)
• PKCepsilon plays a critical role in the regulation of ADAM12 cell-surface expression (PMID:15364951)
• a mutually reinforcing signaling loop sustains the activation of beta1 integrins, PKCepsilon, and PKB/Akt in adherent prostate cancer cells (PMID:15467757)
• We analyzed the dependence of the expression of some selected protein kinase C isoenzymes on the availability and/or action of androgens. (PMID:15499829)
• central role of PKC isoforms and the negative regulatory function of c-Src in the control of stromelysin 3 expression (PMID:15509588)
• PAR1 seems to be the responsible receptor for thrombin-induced migration and adhesion of human colon carcinoma cells including PKCepsilon as an essential signal transducer (PMID:15559761)
• diacylglycerol-responsive PKC isoforms differentially influence CaR agonist-induced release of Ca2+ from internal stores (PMID:15572354)
• two fatty acids inhibited the phorbol 12-myristate 13-acetate (PMA)-induced plasma membrane translocation of protein kinase C (PKC)-alpha and -epsilon (PMID:15627650)
• DGK interacts selectively with and is phosphorylated by PKCepsilon and -eta and peptide agonist-induced selective activation of PKCepsilon directly leads to DGK translocation (PMID:15632189)
• Results demonstrate that a branched signaling pathway involving MEK, ERK, PKCepsilon, PKCalpha, and caveolin-1 regulates collagen expression in normal lung tissue and is perturbed during fibrosis. (PMID:15691837)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkcea	ENSDARG00000003008
danio_rerio	prkceb	ENSDARG00000069928
mus_musculus	Prkce	ENSMUSG00000045038
rattus_norvegicus	Prkce	ENSRNOG00000015603
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), PRKCB (ENSG00000166501)

Protein

Protein identifiers

Protein kinase C epsilon type — Q02156 (reviewed: Q02156)

Alternative names: nPKC-epsilon

All UniProt accessions (4): C9JR22, E9PBI2, Q02156, L7RTI5

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells. Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking.

Subunit / interactions. Forms a ternary complex with TRIM63 and RACK1/GN2BL1. Can form a complex with PDLIM5 and N-type calcium channel. Interacts with COPB1. Interacts with DGKQ. Interacts with STAT3. Interacts with YWHAB. Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner. Interacts (via phorbol-ester/DAG-type 2 domain) with PRPH and VIM. Interacts with NLRP5/MATER. Interacts with PRKCH upstream open reading frame 2; the interaction leads to inhibition of kinase activity.

Subcellular location. Cytoplasm. Cytoskeleton. Cell membrane. Perinuclear region. Nucleus.

Tissue specificity. Expressed in cumulus cells (at protein level).

Post-translational modifications. Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation on Ser-729. Phosphorylation in the hinge domain at Ser-350 by MAPK11 or MAPK14, Ser-346 by GSK3B and Ser-368 by autophosphorylation is required for interaction with YWHAB. In response to growth factors, phosphorylated at Thr-703 and Ser-729 by the mTORC2 complex, promoting autophosphorylation and activation of PRKCE.

Activity regulation. Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-566 (activation loop of the kinase domain), Thr-710 (turn motif) and Ser-729 (hydrophobic region), need to be phosphorylated for its full activation. Inhibited by PRKCH upstream open reading frame 2.

Domain organisation. The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a non-calcium binding domain.

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

RefSeq proteins (1): NP_005391* (*=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
IPR014376	Prot_kin_PKC_delta	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR020454	DAG/PE-bd	Domain
IPR027274	PKC_epsilon	Family
IPR034669	nPKC_epsilon	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 (38 total): modified residue 16, sequence variant 5, mutagenesis site 5, domain 3, binding site 2, zinc finger region 2, region of interest 2, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2WH0	X-RAY DIFFRACTION	2.25
5LIH	X-RAY DIFFRACTION	3.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02156-F1	80.45	0.47

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): 532 (proton acceptor)

Ligand- & substrate-binding residues (2): 414–422; 437

Post-translational modifications (16): 62, 228, 234, 309, 316, 329, 337, 346, 349, 350, 368, 388, 566, 703, 710, 729

Mutagenesis-validated functional residues (5):

Position	Phenotype
437	abolishes activity and s-729 phosphorylation.
566	abolishes phosphorylation by pdpk1/pdk1, and s-729 phosphorylation.
566	no effect on s-729 phosphorylation.
710	no effect on activity; no effect on s-729 phosphorylation.
729	enhances t-566 dephosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-114508	Effects of PIP2 hydrolysis
R-HSA-1250196	SHC1 events in ERBB2 signaling
R-HSA-1489509	DAG and IP3 signaling
R-HSA-2029485	Role of phospholipids in phagocytosis
R-HSA-418597	G alpha (z) signalling events
R-HSA-109582	Hemostasis
R-HSA-1227986	Signaling by ERBB2
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-416476	G alpha (q) signalling events
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 581 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_RESPONSE_TO_ETHANOL, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, TAATAAT_MIR126, REACTOME_INNATE_IMMUNE_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_NEGATIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_PROSTAGLANDIN_E, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS

GO Biological Process (47): MAPK cascade (GO:0000165), macrophage activation involved in immune response (GO:0002281), apoptotic process (GO:0006915), signal transduction (GO:0007165), toxin catabolic process (GO:0009407), positive regulation of epithelial cell migration (GO:0010634), positive regulation of fibroblast migration (GO:0010763), positive regulation of cell-substrate adhesion (GO:0010811), insulin secretion (GO:0030073), positive regulation of actin filament polymerization (GO:0030838), negative regulation of protein ubiquitination (GO:0031397), cell-substrate adhesion (GO:0031589), lipopolysaccharide-mediated signaling pathway (GO:0031663), positive regulation of insulin secretion (GO:0032024), positive regulation of synaptic transmission, GABAergic (GO:0032230), positive regulation of cytokinesis (GO:0032467), positive regulation of superoxide anion generation (GO:0032930), regulation of actin cytoskeleton organization (GO:0032956), intracellular signal transduction (GO:0035556), locomotory exploration behavior (GO:0035641), TRAM-dependent toll-like receptor 4 signaling pathway (GO:0035669), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), xenobiotic catabolic process (GO:0042178), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), response to morphine (GO:0043278), positive regulation of MAPK cascade (GO:0043410), positive regulation of lipid catabolic process (GO:0050996), regulation of release of sequestered calcium ion into cytosol (GO:0051279), cell division (GO:0051301), establishment of localization in cell (GO:0051649), synaptic transmission, GABAergic (GO:0051932), regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061178), mucus secretion (GO:0070254), positive regulation of mucus secretion (GO:0070257), cellular response to ethanol (GO:0071361), cellular response to prostaglandin E stimulus (GO:0071380), cellular response to hypoxia (GO:0071456), positive regulation of wound healing (GO:0090303), negative regulation of sodium ion transmembrane transport (GO:1902306), positive regulation of protein localization to plasma membrane (GO:1903078)

GO Molecular Function (18): actin monomer binding (GO:0003785), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), diacylglycerol-dependent, calcium-independent serine/threonine kinase activity (GO:0004699), ATP binding (GO:0005524), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), signaling receptor activator activity (GO:0030546), ethanol binding (GO:0035276), 14-3-3 protein binding (GO:0071889), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (13): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), intermediate filament cytoskeleton (GO:0045111), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), cell periphery (GO:0071944), cytoskeleton (GO:0005856), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Signal Transduction	3
GPCR downstream signalling	2
G alpha (q) signalling events	1
Platelet activation, signaling and aggregation	1
Signaling by ERBB2	1
Intracellular signaling by second messengers	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Signaling by Receptor Tyrosine Kinases	1
Immune System	1
Innate Immune System	1
Signaling by GPCR	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	5
intracellular membrane-bounded organelle	4
positive regulation of cell migration	2
intracellular anatomical structure	2
protein kinase activity	2
catalytic activity	2
molecular function activator activity	2
protein binding	2
endomembrane system	2
intracellular signaling cassette	1
myeloid cell activation involved in immune response	1
leukocyte activation involved in immune response	1
immune response	1
macrophage activation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
catabolic process	1
toxin metabolic process	1
detoxification	1
epithelial cell migration	1
regulation of epithelial cell migration	1
fibroblast migration	1
regulation of fibroblast migration	1
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
positive regulation of cell adhesion	1
protein secretion	1
peptide hormone secretion	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1

Protein interactions and networks

STRING

1932 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKCE	A0A0A0MSP3	A0A0A0MSP3	867
PRKCE	RACK1	P25388	708
PRKCE	CACNA1B	Q00975	685
PRKCE	COPB2	P35606	648
PRKCE	STAT3	P40763	597
PRKCE	IRS2	Q9Y4H2	553
PRKCE	SIRT3	Q9NTG7	540
PRKCE	ELOVL6	Q9H5J4	536
PRKCE	ECE1	P42892	532
PRKCE	ECE2	P0DPD6	528
PRKCE	TRPV1	Q8NER1	523
PRKCE	TRPA1	O75762	507
PRKCE	PPARG	P37231	507
PRKCE	GRHL3	Q8TE85	493
PRKCE	BRAF	P15056	493

IntAct

52 interactions, top by confidence:

A	B	Type	Score
CHUK	IKBKB	psi-mi:“MI:0914”(association)	0.960
PRKCE	YWHAZ	psi-mi:“MI:0407”(direct interaction)	0.730
YWHAZ	PRKCE	psi-mi:“MI:0914”(association)	0.730
PRKCE	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.640
PRKCE	BRAF	psi-mi:“MI:0915”(physical association)	0.590
APP	PRKCE	psi-mi:“MI:0915”(physical association)	0.560
SNCA	PRKCE	psi-mi:“MI:0915”(physical association)	0.560
YWHAE	PRKCE	psi-mi:“MI:0915”(physical association)	0.560
SFN	PRKCE	psi-mi:“MI:0915”(physical association)	0.560
PRKCE	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
EGFR	PRKCE	psi-mi:“MI:0915”(physical association)	0.550
PAPOLG	ZFC3H1	psi-mi:“MI:0914”(association)	0.530
PRKCE	MAPKAP1	psi-mi:“MI:0915”(physical association)	0.520
TICAM2	PRKCE	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PRKCE	PRKCE	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PRKD1	PRKCE	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PECAM1	PRKCE	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (174): PRKCE (Affinity Capture-Western), ZBTB16 (Affinity Capture-Western), NANOG (Biochemical Activity), PRKCE (Two-hybrid), BAD (Affinity Capture-Western), PRKCE (Affinity Capture-Western), BCL6 (Affinity Capture-Western), IL32 (Affinity Capture-Western), PRKCE (PCA), HSP90AA1 (Affinity Capture-Western), TOMM20 (Affinity Capture-Western), PRKCE (Affinity Capture-RNA), RASGRP3 (Biochemical Activity), GAD2 (Biochemical Activity), GAD1 (Biochemical Activity)

ESM2 similar proteins: A8KBH6, B6CZ17, B6CZ18, O75582, P04409, P05126, P05128, P05129, P05130, P05696, P05771, P05772, P09215, P09216, P10102, P10829, P10830, P13677, P13678, P16054, P17252, P20444, P23298, P24723, P28867, P34722, P34885, P54644, P63318, P63319, P68403, P68404, P90980, Q02111, Q02156, Q05655, Q16974, Q16975, Q17941, Q1XHL7

Diamond homologs: A0JNJ1, A1CEK6, A1DFN5, A2QW93, A4RF61, A6QLK6, A7A261, F1LRS8, O35179, O35964, O43307, O74749, O75791, O75886, O88811, O89100, O93436, P02549, P07751, P09215, P09216, P10830, P13395, P16054, P16086, P16546, P23298, P24723, P28867, P29355, P32793, P34885, P38753, P43603, P53281, P62993, P62994, P70297, P87379, P97306

SIGNOR signaling

86 interactions.

A	Effect	B	Mechanism
PDPK1	up-regulates	PRKCE	phosphorylation
PRKCE	down-regulates	PRKCE	phosphorylation
PRKCE	up-regulates	IQGAP1	phosphorylation
PRKCE	up-regulates	CHAT	phosphorylation
PRKCE	up-regulates	STAT3	phosphorylation
PRKCE	up-regulates	GJA1	phosphorylation
PRKCE	up-regulates	TICAM2	phosphorylation
PRKCE	down-regulates	KIR3DL1	phosphorylation
PRKCE	down-regulates	BAD	phosphorylation
PRKCE	down-regulates	CTNND1	phosphorylation
PRKCE	up-regulates	OCLN	phosphorylation
GSK3B	up-regulates	PRKCE	phosphorylation
“bisindolylmaleimide i”	down-regulates	PRKCE	“chemical inhibition”
3-(1-methyl-3-indolyl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-3-indolyl]pyrrole-2,5-dione	down-regulates	PRKCE	“chemical inhibition”
PRKCE	up-regulates	ATF2	phosphorylation
PRKCE	up-regulates	FGFR1	phosphorylation
PRKCE	up-regulates	FGFR2	phosphorylation
1,2-diacyl-sn-glycerol	“up-regulates activity”	PRKCE	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 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
Apoptosis	5	24.7×	2e-04
Programmed Cell Death	5	21.5×	3e-04
SARS-CoV-2 activates/modulates innate and adaptive immune responses	5	13.1×	1e-03
Transcriptional Regulation by TP53	5	9.1×	3e-03
Signaling by Receptor Tyrosine Kinases	5	7.6×	7e-03
Cytokine Signaling in Immune system	5	6.0×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
protein phosphorylation	8	14.3×	4e-05
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	10.3×	7e-03
intracellular signal transduction	8	8.0×	1e-03
negative regulation of apoptotic process	7	6.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	41
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
453227	NM_005400.3(PRKCE):c.1795G>A (p.Glu599Lys)	Pathogenic
4071986	NM_005400.3(PRKCE):c.982G>C (p.Glu328Gln)	Likely pathogenic

SpliceAI

6176 predictions. Top by Δscore:

Variant	Effect	Δscore
2:45652447:GG:G	donor_gain	1.0000
2:45652448:GG:G	donor_gain	1.0000
2:45652449:G:A	donor_loss	1.0000
2:45652449:G:GG	donor_gain	1.0000
2:45652450:T:A	donor_loss	1.0000
2:45842994:TTGCA:T	acceptor_loss	1.0000
2:45842995:TGCA:T	acceptor_loss	1.0000
2:45842996:GCAG:G	acceptor_loss	1.0000
2:45842997:CAGA:C	acceptor_loss	1.0000
2:45842998:A:AG	acceptor_gain	1.0000
2:45842998:AGA:A	acceptor_loss	1.0000
2:45842999:G:GG	acceptor_gain	1.0000
2:45976410:T:TA	acceptor_gain	1.0000
2:45976416:T:TA	acceptor_gain	1.0000
2:45976424:CCCAG:C	acceptor_loss	1.0000
2:45976427:A:AG	acceptor_gain	1.0000
2:45976428:G:GA	acceptor_gain	1.0000
2:45976428:GC:G	acceptor_gain	1.0000
2:45976428:GCC:G	acceptor_gain	1.0000
2:45976428:GCCC:G	acceptor_gain	1.0000
2:45976428:GCCCC:G	acceptor_gain	1.0000
2:45976584:ATCTG:A	donor_gain	1.0000
2:45976585:TCTG:T	donor_gain	1.0000
2:45976585:TCTGG:T	donor_loss	1.0000
2:45976586:CTGG:C	donor_loss	1.0000
2:45976588:GGTAA:G	donor_loss	1.0000
2:45976589:G:GG	donor_gain	1.0000
2:45976589:GTAAG:G	donor_loss	1.0000
2:45976590:T:G	donor_loss	1.0000
2:45978974:AGG:A	acceptor_gain	1.0000

AlphaMissense

4898 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:45652348:T:A	V83D	1.000
2:45652386:G:C	A96P	1.000
2:45976507:T:A	V164D	1.000
2:45976509:C:G	H165D	1.000
2:45976524:C:G	H170D	1.000
2:45976526:C:A	H170Q	1.000
2:45976526:C:G	H170Q	1.000
2:45976530:T:A	F172I	1.000
2:45976530:T:C	F172L	1.000
2:45976531:T:C	F172S	1.000
2:45976531:T:G	F172C	1.000
2:45976532:C:A	F172L	1.000
2:45976532:C:G	F172L	1.000
2:45976537:C:A	A174D	1.000
2:45976563:T:A	C183S	1.000
2:45976563:T:C	C183R	1.000
2:45976564:G:A	C183Y	1.000
2:45976564:G:C	C183S	1.000
2:45976564:G:T	C183F	1.000
2:45976565:C:G	C183W	1.000
2:45976572:T:A	C186S	1.000
2:45976572:T:C	C186R	1.000
2:45976573:G:A	C186Y	1.000
2:45976573:G:C	C186S	1.000
2:45976573:G:T	C186F	1.000
2:45976574:C:G	C186W	1.000
2:45976582:T:C	F189S	1.000
2:45976587:T:A	W191R	1.000
2:45976587:T:C	W191R	1.000
2:45978977:G:C	G192R	1.000

dbSNP variants (sampled 300 via entrez): RS1000007912 (2:45892945 C>T), RS1000011954 (2:46117558 A>C), RS1000014163 (2:45914152 A>T), RS1000022930 (2:45675333 G>C), RS1000028228 (2:46126943 T>G), RS1000041858 (2:46047743 T>C), RS1000044792 (2:45706670 G>A,C,T), RS1000052786 (2:45946220 C>G,T), RS1000058985 (2:45818854 C>A,T), RS1000061770 (2:46004062 G>A), RS1000065139 (2:45842227 G>A,T), RS1000066379 (2:46158123 C>G), RS1000066973 (2:45901081 G>A), RS1000081994 (2:46127227 C>G,T), RS1000087530 (2:45744446 T>C,G)

Disease associations

OMIM: gene MIM:176975 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

91 associations (top):

Study	Trait	p-value
GCST000499_3	Hemoglobin	7.000000e-13
GCST000502_5	Hematocrit	4.000000e-15
GCST000583_27	Hematological and biochemical traits	5.000000e-06
GCST000583_29	Hematological and biochemical traits	5.000000e-07
GCST000588_6	Red blood cell count	4.000000e-08
GCST000854_4	Suicide risk	8.000000e-06
GCST001765_37	Red blood cell traits	3.000000e-19
GCST001873_2	Red blood cell traits	4.000000e-09
GCST002119_20	Metabolite levels (X-11787)	8.000000e-06
GCST002875_30	Diisocyanate-induced asthma	2.000000e-06
GCST002951_1	Response to zileuton treatment in asthma (FEV1 change interaction)	1.000000e-06
GCST003074_7	Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging)	9.000000e-07
GCST003648_3	Pathological gambling	6.000000e-06
GCST003938_1	Carotenoid levels (alpha-carotene)	1.000000e-08
GCST004003_6	Hematocrit	1.000000e-19
GCST004005_5	Hemoglobin levels	1.000000e-20
GCST004008_13	Red blood cell count	1.000000e-06
GCST004008_4	Red blood cell count	1.000000e-08
GCST004068_38	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	7.000000e-06
GCST004278_18	Pulse pressure	4.000000e-12
GCST004280_66	Diastolic blood pressure	4.000000e-07
GCST004330_2	Hematocrit	3.000000e-09
GCST004331_1	Hemoglobin	3.000000e-08
GCST004412_1	Craniofacial microsomia	1.000000e-17
GCST004601_18	Red blood cell count	3.000000e-15
GCST004601_19	Red blood cell count	2.000000e-39
GCST004601_20	Red blood cell count	1.000000e-24
GCST004601_21	Red blood cell count	4.000000e-66
GCST004604_22	Hematocrit	3.000000e-16
GCST004604_23	Hematocrit	2.000000e-10

EFO canonical traits (25, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count
EFO:0004321	attempted suicide
EFO:0005276	hydroxy-leucine measurement
EFO:0006995	response to diisocyanate
EFO:0005921	FEV change measurement
EFO:0007707	cerebral amyloid deposition measurement
EFO:0007893	alpha-carotene measurement
EFO:0005763	pulse pressure measurement
EFO:0006336	diastolic blood pressure
EFO:0007986	reticulocyte count
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0008392	triiodothyronine measurement
EFO:0004338	body weight
EFO:0004340	body mass index
EFO:0010543	uridine diphosphate galactose measurement
EFO:0010544	uridine diphosphate glucose measurement
EFO:0004980	appendicular lean mass
EFO:0005091	monocyte count
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2096620 (PROTEIN FAMILY), CHEMBL3582 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

21 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 399,562 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL265502	SURAMIN	3	36,848
CHEMBL38380	FASUDIL	3	11,953
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL140	CURCUMIN	3	93,882
CHEMBL2107337	ENZASTAURIN HYDROCHLORIDE	3	516
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL603469	LESTAURTINIB	3
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
CHEMBL3982723	DAROVASERTIB	2	473
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL494089	GSK-690693	1

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11125035	Toxicity	3	radiotherapy
rs11125039	Toxicity	3	sorafenib	Hypertension

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs940052	PRKCE		0.00	0
rs2278773	PRKCE		0.00	0
rs6720975	PRKCE		0.00	0
rs11125035	PRKCE	3	3.00	1	radiotherapy
rs11125039	PRKCE	3	2.50	1	sorafenib

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Eta subfamily

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
ingenol mebutate	Activation	9.77	pKi
10-Me-Aplog-1	Activation	8.7	pKi
sotrastaurin	Inhibition	8.21	pIC50
balanol	Inhibition	7.7	pIC50
RasGRP activator 1	Binding	7.68	pKi
chelerythrine	Inhibition	7.62	pIC50
Ro-32-0432	Inhibition	6.97	pIC50
ninvosudil	Inhibition	6.47	pIC50
7-hydroxystaurosporine	Inhibition	6.28	pIC50

Binding affinities (BindingDB)

93 measured of 130 human assays (132 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4442196	IC50	0.09 nM
CHEMBL3741746	IC50	0.13 nM
CHEMBL4528495	IC50	0.15 nM
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
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
maleimide derivative, 12	IC50	0.9 nM
Staurosporine	KD	1.7 nM
AEB071	IC50	2.1 nM
maleimide derivative, 10	IC50	2.2 nM
2-[1-(3-dimethylaminopropyl)-indol-3-yl]-3-(indol-3-yl)maleimide	IC50	2.3 nM
maleimide derivative, 11	IC50	7.1 nM
maleimide derivative, 9	IC50	15 nM
2-{[2,6-dihydroxy-4-({[(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	22 nM
2-{[2,6-dihydroxy-4-({[(1R,2S)-2-[(4-hydroxyphenyl)methyl]cyclopentyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	30 nM
2-{[2,6-dihydroxy-4-({[(1R,2R)-2-[(4-hydroxybenzene)amido]cyclopentyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	40 nM
2-({2,6-dihydroxy-4-[({2-[(4-hydroxybenzene)amido]cyclopentyl}oxy)carbonyl]phenyl}carbonyl)-3-hydroxybenzoic acid	IC50	40 nM
2-({2,6-dihydroxy-4-[({3-[(4-hydroxybenzene)amido]bicyclo[2.2.1]heptan-2-yl}oxy)carbonyl]phenyl}carbonyl)-3-hydroxybenzoic acid	IC50	55 nM
2-({2,6-dihydroxy-4-[({3-[(4-hydroxybenzene)amido]azepan-4-yl}oxy)carbonyl]phenyl}carbonyl)-3-hydroxybenzoic acid	IC50	67 nM
maleimide derivative, 5	IC50	73 nM
maleimide derivative, 3	IC50	98 nM
2-{[2,6-dihydroxy-4-({[(8R,9R)-9-[(4-hydroxybenzene)amido]tricyclo[5.2.1.0^{2,6}]decan-8-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	100 nM
trans-2-[3,5-Dihydroxy-4-[2-hydroxy-6-(trifluoromethanesulfonylamino)benzoyl]benzoyloxy]-1-(4-hydroxybenzamido)cyclopentane	IC50	100 nM
(+-)-2-[[2,6-Dihydroxy-4-[[[3-(4-hydroxyphenyl)-2-[(phenylsulfonyl)amino]propyl]oxy]carbonyl]phenyl]carbonyl]-3-hydroxybenzoic Acid	IC50	110 nM
(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl 4-[(2-{[(acetyloxy)methoxy]carbonyl}-6-hydroxyphenyl)carbonyl]-3,5-dihydroxybenzoate	IC50	130 nM
2-{[2,6-dihydroxy-4-({[(1R,2R)-2-[(4-hydroxyphenyl)methyl]cyclopentyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	160 nM
(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl 4-{[2-({[(2,2-dimethylpropanoyl)oxy]methoxy}carbonyl)-6-hydroxyphenyl]carbonyl}-3,5-dihydroxybenzoate	IC50	160 nM
PKC-412	KD	190 nM
2-[(4-{[(2S)-2-benzenesulfonamido-3-(4-hydroxyphenyl)propoxy]carbonyl}-2,6-dihydroxyphenyl)carbonyl]-3-hydroxybenzoic acid	IC50	210 nM
(1R,2R)-2-[(4-hydroxybenzene)amido]cyclopentyl 3,5-dihydroxy-4-[2-hydroxy-6-(methoxycarbonyl)phenoxy]benzoate	IC50	210 nM
2-{[2,6-dihydroxy-4-({[(1R,2R)-2-(4-hydroxyphenoxy)cyclopentyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	220 nM
(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl 3,5-dihydroxy-4-{[2-hydroxy-6-(methoxycarbonyl)phenyl]carbonyl}benzoate	IC50	250 nM
(+-)-anti-3-[[4-(6-Carboxy-2-hydroxybenzoyl)-3,5-hydroxybenzoyl]oxy]-4-(4-hydroxybenzyl)pyrrolidine, Trifluoroacetic Acid Salt	IC50	260 nM
2-{[2,6-dihydroxy-4-({[(1R,2R)-2-[(4-hydroxybenzene)amido]cycloheptyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	270 nM
2-[(4-hydroxybenzene)amido]cyclopentyl 3,5-dihydroxy-4-{[2-hydroxy-6-(methoxycarbonyl)phenyl]carbonyl}benzoate	IC50	320 nM
trans-2-[4-(6-Hydroxy-2-tetrazolylbenzoyl)-3,5-dihydroxybenzoyloxy]-1-(4-hydroxybenzamido)cyclopentane	IC50	340 nM
2-({2,6-dihydroxy-4-[({3-[(4-hydroxybenzene)amido]-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl}oxy)carbonyl]phenyl}carbonyl)-3-hydroxybenzoic acid	IC50	410 nM
(+-)-2-[[2,6-Dihydroxy-4-[[[3-(4-hydroxyphenyl)-1-methylpropyl]oxy]carbonyl]phenyl]carbonyl]-3-hydroxybenzoic Acid	IC50	410 nM
2-{[2,6-dihydroxy-4-({[(4S)-3-[(4-hydroxybenzene)amido]-1-azabicyclo[3.2.2]nonan-4-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	415 nM
trans-4-[4-(2-Hydroxy-5,6,7,8-tetrahydro-1-naphthoyl)-3,5-dihydroxybenzoyloxy]-3-(4-hydroxybenzamido)pyrrolidine	IC50	430 nM
2-{[2,6-dihydroxy-4-({[(1R,2R)-2-[(4-hydroxybenzene)amido]cyclopentyl]oxy}methyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	460 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
(3R,4R)-3-[(4-hydroxybenzene)amido]azepan-4-yl 4-[(2,6-dihydroxyphenyl)carbonyl]-3,5-dihydroxybenzoate	IC50	860 nM
(1R,2R)-2-[(4-hydroxybenzene)amido]cyclopentyl 4-{[2-(ethoxycarbonyl)-6-hydroxyphenyl]carbonyl}-3,5-dihydroxybenzoate	IC50	920 nM
(1R,2S)-2-[(4-hydroxyphenyl)methyl]cyclopentyl 3,5-dihydroxy-4-{[2-hydroxy-6-(methoxycarbonyl)phenyl]carbonyl}benzoate	IC50	1400 nM

ChEMBL bioactivities

783 potent at pChembl≥5 of 909 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
9.89	IC50	0.13	nM	CHEMBL3741746
9.85	IC50	0.14	nM	CHEMBL4575056
9.85	IC50	0.143	nM	STAUROSPORINE
9.82	IC50	0.15	nM	CHEMBL4528495
9.77	IC50	0.17	nM	CHEMBL4538431
9.74	IC50	0.18	nM	CHEMBL4443190
9.72	EC50	0.19	nM	CHEMBL3741746
9.70	IC50	0.198	nM	STAUROSPORINE
9.66	Kd	0.22	nM	CHEMBL27768
9.66	IC50	0.22	nM	CHEMBL4435580
9.60	Kd	0.25	nM	STAUROSPORINE
9.54	IC50	0.286	nM	STAUROSPORINE
9.44	IC50	0.36	nM	CHEMBL4587471
9.43	Kd	0.37	nM	CHEMBL337834
9.35	Ki	0.45	nM	PHORBOL MYRISTATE ACETATE
9.33	Ki	0.47	nM	CHEMBL399981
9.26	EC50	0.55	nM	CHEMBL4587471
9.26	Ki	0.55	nM	CHEMBL337834
9.24	Ki	0.58	nM	CHEMBL265998
9.23	Kd	0.59	nM	CHEMBL27768
9.22	IC50	0.6	nM	STAUROSPORINE
9.22	EC50	0.6	nM	CHEMBL4575056
9.20	Ki	0.63	nM	DEBROMOAPLYSIATOXIN
9.15	IC50	0.7	nM	CHEMBL2151411
9.09	Kd	0.81	nM	CHEMBL27768
9.05	IC50	0.9	nM	CHEMBL1996510
9.00	Ki	1	nM	CHEMBL2326002
9.00	IC50	1	nM	STAUROSPORINE
9.00	Ki	1	nM	CHEMBL285801
8.99	Ki	1.03	nM	CHEMBL137386
8.92	Ki	1.21	nM	CHEMBL3393748
8.89	Ki	1.3	nM	DEMETHOXYDEBROMOAPLYSIATOXIN
8.89	Ki	1.3	nM	APLYSIATOXIN
8.87	Ki	1.35	nM	CHEMBL27768
8.85	Ki	1.43	nM	CHEMBL137386
8.82	Kd	1.5	nM	CHEMBL27768
8.82	IC50	1.5	nM	STAUROSPORINE
8.80	IC50	1.6	nM	CHEMBL1080994
8.77	IC50	1.7	nM	CHEMBL291126
8.72	Ki	1.89	nM	CHEMBL137386
8.70	IC50	2	nM	CHEMBL162621
8.70	IC50	2	nM	STAUROSPORINE
8.70	Ki	2	nM	CHEMBL2148108
8.70	IC50	2	nM	CHEMBL2153750
8.70	IC50	2	nM	CHEMBL1084411
8.67	Ki	2.14	nM	CHEMBL3393741
8.66	Ki	2.17	nM	CHEMBL3289012
8.66	IC50	2.2	nM	CHEMBL83790

PubChem BioAssay actives

618 with measured affinity, of 2339 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
[(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	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	kd	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
[(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	218937: Inhibition of [3H]-phorbol 12,13-dibutyrate (PDBu) binding to human recombinant protein kinase C epsilon	ki	0.0004	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	163699: Binding affinity for human Protein kinase C epsilon	kd	0.0004	uM
(10S,13S)-3-hexyl-13-(hydroxymethyl)-9-methyl-10-propan-2-yl-3,9,12-triazatricyclo[6.6.1.04,15]pentadeca-1,4(15),5,7-tetraen-11-one	312188: Displacement of [3H]PDBu from PKCepsilon C1B domain	ki	0.0005	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	163849: Displacement of 3[H]PDBu from Protein kinase C epsilon C1b domain	ki	0.0006	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	687833: Inhibition of [3H]PDBu binding to PKCepsilon C1B domain	ki	0.0006	uM
3-(7-methyl-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	690001: Inhibition of PKCepsilon by scintillation proximity assay	ic50	0.0007	uM
3-(1H-indol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	690001: Inhibition of PKCepsilon by scintillation proximity assay	ic50	0.0009	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	163837: Displacement of [3H]- PDBu from recombinant PKC epsilon expressed in baculovirus	ki	0.0010	uM
(2R)-2-[(2S)-4-[3-chloro-5-fluoro-6-(2H-pyrazolo[3,4-b]pyridin-3-yl)-2-pyridinyl]piperazin-2-yl]-3-methylbutan-2-ol	728534: Inhibition of PKC epsilon (unknown origin)	ki	0.0010	uM
[(4E)-2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hexylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0010	uM
[(4E)-2-(hydroxymethyl)-4-(3-methylbutylidene)-5-oxooxolan-2-yl]methyl 5-methyl-3-(2-methylpropyl)hexanoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0012	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	517267: Inhibition of [3H]PDBu binding to PKCepsilon C1B peptide	ki	0.0013	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	768062: Displacement of [3H]PDBu from PKCepsilon C1B domain (unknown origin)	ki	0.0013	uM
4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-[3-(4-methylpiperazin-1-yl)sulfonylphenyl]ethenyl]pyridine-3-carbonitrile	469099: Inhibition of PKCepsilon	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
4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-[6-[(4-methylpiperazin-1-yl)methyl]-2-pyridinyl]ethenyl]pyridine-3-carbonitrile	463342: Inhibition of PKCepsilon	ic50	0.0020	uM
3-[6-fluoro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	690001: Inhibition of PKCepsilon by scintillation proximity assay	ic50	0.0020	uM
(1R,3R,4R,5S,9R,13R)-9-(hydroxymethyl)-3-[4-(3-hydroxyphenyl)butyl]-4,16,16-trimethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	687833: Inhibition of [3H]PDBu binding to PKCepsilon C1B domain	ki	0.0020	uM
[(4E)-2-(hydroxymethyl)-4-(3-methylbutylidene)-5-oxooxolan-2-yl]methyl (9E,12E)-octadeca-9,12-dienoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0021	uM
[(4E)-2-(hydroxymethyl)-4-[(1-methylindol-5-yl)methylidene]-5-oxooxolan-2-yl]methyl 2-propylpentanoate	1152263: Displacement of [3H]PDBu from recombinant human PKC-epsilon after 5 mins by scintillation counting analysis in presence of phosphatidylserine	ki	0.0022	uM
[(4Z)-2-(hydroxymethyl)-4-(3-methylbutylidene)-5-oxooxolan-2-yl]methyl 5-methyl-3-(2-methylpropyl)hexanoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0024	uM
4-[(4-methyl-1H-indol-5-yl)amino]-5-[5-[(4-methylpiperazin-1-yl)methyl]-1-benzofuran-2-yl]pyridine-3-carbonitrile	447961: Inhibition of PKCepsilon by IMAP fluorescence polarization technology	ic50	0.0025	uM
4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-4-piperazin-1-ylbut-1-enyl]pyridine-3-carbonitrile	453670: Inhibition of PKCepsilon by fluorescence polarization assay	ic50	0.0025	uM
[(4E)-4-[(4-chlorophenyl)methylidene]-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1505437: Displacement of [3H]PDBu from full length recombinant human PKCepsilon expressed in baculovirus expression system after 5 mins by scintillation counting	ki	0.0026	uM
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	2098509: Inhibition of PKCepsilon (unknown origin)	ic50	0.0029	uM
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	1902443: Inhibition of PKCepsilon (unknown origin) by IMAP kinase assay	ic50	0.0032	uM
3-(1-methylindol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	690001: Inhibition of PKCepsilon by scintillation proximity assay	ic50	0.0038	uM
3-[6-chloro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	690001: Inhibition of PKCepsilon by scintillation proximity assay	ic50	0.0039	uM
[(4E)-2-(hydroxymethyl)-4-[(9Z,12Z)-octadeca-9,12-dienylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0041	uM
3-(1H-indol-3-yl)-4-[3-(4-methylpiperazin-1-yl)isoquinolin-1-yl]pyrrole-2,5-dione	690001: Inhibition of PKCepsilon by scintillation proximity assay	ic50	0.0043	uM
3-[2-chloro-6-[(dimethylamino)methyl]naphthalen-1-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	1437220: Inhibition of PKCepsilon (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0043	uM
[(4E)-2-(hydroxymethyl)-4-(3-methylbutylidene)-5-oxooxolan-2-yl]methyl octadec-9-ynoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0048	uM
N’-(3-pyridin-4-yl-2,6-naphthyridin-1-yl)ethane-1,2-diamine	688997: Inhibition of recombinant human PKCepsilon assessed as [33P]-ATP incorporation into tridecapeptide substrate after 60 mins by scintillation proximity assay	ic50	0.0050	uM
(2S)-1-N-(3-pyridin-4-yl-2,6-naphthyridin-1-yl)propane-1,2-diamine	688997: Inhibition of recombinant human PKCepsilon assessed as [33P]-ATP incorporation into tridecapeptide substrate after 60 mins by scintillation proximity assay	ic50	0.0050	uM
[(4Z)-2-(hydroxymethyl)-4-[(9Z,12Z)-octadeca-9,12-dienylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0051	uM
[(4E)-2-(hydroxymethyl)-4-(3-methylbutylidene)-5-oxooxolan-2-yl]methyl octadeca-9,11-diynoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0052	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	625014: Binding constant for PRKCE kinase domain	kd	0.0053	uM
2-[2,6-dihydroxy-4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	254306: Inhibitory constant against protein kinase C	ki	0.0053	uM
[(4E)-2-(hydroxymethyl)-4-(3-methylbutylidene)-5-oxooxolan-2-yl]methyl 8-[2-[(2-pentylcyclopropyl)methyl]cyclopropyl]octanoate	1189624: Displacement of [20-3H] phorbol 12, 13-dibutylate from recombinant PKCepsilon (unknown origin) in presence of 100 ug/ml 100% phosphatidylserine	ki	0.0055	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	0.0055	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	increases activity, increases localization, affects reaction, increases expression, affects localization (+1 more)	4
Aflatoxin B1	affects methylation, decreases expression, decreases methylation	4
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	3
Curcumin	decreases response to substance, decreases expression, decreases reaction, increases expression	3
Estradiol	affects cotreatment, decreases expression, affects binding, increases reaction, increases expression	3
bisphenol A	decreases methylation, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Calcium	increases abundance, increases activity, increases reaction, increases phosphorylation, decreases reaction (+1 more)	2
Formaldehyde	decreases expression	2
Thiram	decreases activity, increases expression	2
Valproic Acid	affects cotreatment, increases expression	2
Palmitic Acid	increases phosphorylation	2
FR900359	affects phosphorylation	1
methyleugenol	decreases expression	1
diphenyleneiodonium	affects localization, decreases reaction	1
gingerol	affects reaction, increases expression	1
morin	decreases expression	1
methylparaben	decreases expression	1
chelerythrine	decreases reaction, increases phosphorylation	1
mono-(2-ethylhexyl)phthalate	affects reaction, increases expression	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
puag-haad	decreases reaction, increases expression	1
droloxifene	affects localization	1
di-n-butylphosphoric acid	affects expression	1
bisindolylmaleimide I	decreases reaction, increases expression, decreases expression	1

ChEMBL screening assays

722 unique, capped per target: 707 binding, 14 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
CHEMBL4048341	ADMET	Inhibition of partial length wild type human PRKCE expressed in mammalian expression system at 0.5 uM by KINOMEscan method relative to control	Discovery and Preclinical Development of IIIM-290, an Orally Active Potent Cyclin-Dependent Kinase Inhibitor. — J Med Chem

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7YH	Ubigene A-549 PRKCE KO	Cancer cell line	Male
CVCL_D8TX	Ubigene HCT 116 PRKCE KO	Cancer cell line	Male
CVCL_D9PM	Ubigene HEK293 PRKCE KO	Transformed cell line	Female
CVCL_E0LW	Ubigene HeLa PRKCE KO	Cancer cell line	Female
CVCL_TG84	HAP1 PRKCE (-) 1	Cancer cell line	Male
CVCL_TG85	HAP1 PRKCE (-) 2	Cancer cell line	Male
CVCL_TG86	HAP1 PRKCE (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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