PRKCZ

Summary

PRKCZ (protein kinase C zeta, HGNC:9412) is a protein-coding gene on chromosome 1p36.33, encoding Protein kinase C zeta type (Q05513). Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell pola….

Protein kinase C (PKC) zeta is a member of the PKC family of serine/threonine kinases which are involved in a variety of cellular processes such as proliferation, differentiation and secretion. Unlike the classical PKC isoenzymes which are calcium-dependent, PKC zeta exhibits a kinase activity which is independent of calcium and diacylglycerol but not of phosphatidylserine. Furthermore, it is insensitive to typical PKC inhibitors and cannot be activated by phorbol ester. Unlike the classical PKC isoenzymes, it has only a single zinc finger module. These structural and biochemical properties indicate that the zeta subspecies is related to, but distinct from other isoenzymes of PKC. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 5590 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 29 total — 1 pathogenic
• Phenotypes (HPO): 99
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002744

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9412
Approved symbol	PRKCZ
Name	protein kinase C zeta
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Aliases	PKC2
Ensembl gene	ENSG00000067606
Ensembl biotype	protein_coding
OMIM	176982
Entrez	5590

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 21 protein_coding, 5 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000378567, ENST00000400921, ENST00000419838, ENST00000461106, ENST00000461465, ENST00000466352, ENST00000466651, ENST00000468310, ENST00000470511, ENST00000470596, ENST00000470986, ENST00000471018, ENST00000472017, ENST00000478770, ENST00000479263, ENST00000479566, ENST00000481140, ENST00000482686, ENST00000484419, ENST00000486681, ENST00000495347, ENST00000496325, ENST00000497183, ENST00000503297, ENST00000503672, ENST00000505322, ENST00000877862, ENST00000877863, ENST00000877864, ENST00000926524, ENST00000965048

RefSeq mRNA: 8 — MANE Select: NM_002744 NM_001033581, NM_001033582, NM_001242874, NM_001350803, NM_001350804, NM_001350805, NM_001350806, NM_002744

CCDS: CCDS37, CCDS41229, CCDS55563

Canonical transcript exons

ENST00000378567 — 18 exons

Exon	Start	End
ENSE00002316473	2050411	2050701
ENSE00003481487	2172301	2172388
ENSE00003513439	2169518	2169604
ENSE00003525770	2155995	2156092
ENSE00003561737	2174754	2174833
ENSE00003563170	2055441	2055562
ENSE00003563212	2056484	2056573
ENSE00003609132	2175224	2175313
ENSE00003612876	2184583	2184698
ENSE00003626317	2184922	2185395
ENSE00003640274	2173897	2174016
ENSE00003653496	2135262	2135347
ENSE00003656964	2144210	2144341
ENSE00003659235	2172055	2172190
ENSE00003783979	2150790	2150978
ENSE00003784140	2146027	2146108
ENSE00003789547	2059541	2059591
ENSE00003791533	2148872	2148924

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 98.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.8181 / max 443.6639, expressed in 1177 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165	3.7024	886
166	3.3058	174
164	1.5442	695
171	1.0432	123
167	1.0277	158
173	0.5630	93
174	0.5360	53
177	0.3245	155
168	0.2571	84
172	0.1718	70

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.95	gold quality
cerebellar hemisphere	UBERON:0002245	98.91	gold quality
middle temporal gyrus	UBERON:0002771	98.81	gold quality
cerebellar cortex	UBERON:0002129	98.78	gold quality
cerebellum	UBERON:0002037	98.51	gold quality
right frontal lobe	UBERON:0002810	98.21	gold quality
substantia nigra pars compacta	UBERON:0001965	98.10	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.02	gold quality
prefrontal cortex	UBERON:0000451	97.88	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.88	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.81	gold quality
primary visual cortex	UBERON:0002436	97.75	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.50	gold quality
occipital lobe	UBERON:0002021	97.38	gold quality
frontal cortex	UBERON:0001870	97.25	gold quality
nucleus accumbens	UBERON:0001882	97.24	gold quality
superior frontal gyrus	UBERON:0002661	97.19	gold quality
pons	UBERON:0000988	97.18	gold quality
putamen	UBERON:0001874	97.15	gold quality
neocortex	UBERON:0001950	96.97	gold quality
parietal lobe	UBERON:0001872	96.89	gold quality
cerebral cortex	UBERON:0000956	96.87	gold quality
postcentral gyrus	UBERON:0002581	96.81	gold quality
telencephalon	UBERON:0001893	96.73	gold quality
cingulate cortex	UBERON:0003027	96.71	gold quality
Ammon’s horn	UBERON:0001954	96.62	gold quality
right testis	UBERON:0004534	96.62	gold quality
lateral globus pallidus	UBERON:0002476	96.59	gold quality
anterior cingulate cortex	UBERON:0009835	96.59	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	41.39
E-MTAB-6142	no	1.95
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2, PPARG, SP1

miRNA regulators (miRDB)

12 targeting PRKCZ, 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-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-132-5P	96.61	65.79	115
HSA-MIR-3622B-5P	94.62	64.58	835
HSA-MIR-6774-3P	89.14	65.20	68
HSA-MIR-1307-3P	66.08	59.35	14

Literature-anchored findings (GeneRIF, showing 40)

• Isoforms of protein kinase C and their distribution in human adrenal cortex and tumors (PMID:11740573)
• 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-zeta is required in EGF protection of microtubules and intestinal barrier integrity against oxidant injury. (PMID:11960776)
• role of PKCzeta in T cells through the control of NFAT function by modulating the activity of its transactivation domain (PMID:12021260)
• PKC zeta 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)
• 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)
• shows for the first time that topoisomerase II beta is a substrate for PKC zeta, and that PKC zeta may significantly influence topoisomerase II inhibitor-induced cytotoxicity by altering topoisomerase II beta activity through its kinase function (PMID:12105221)
• EGF protects against oxidative disruption of the intestinal barrier by stabilizing the cytoskeleton in large part through the activation of PKC-zeta and downregulation of iNOS (PMID:12223351)
• The adapter protein ZIP binds Grb14 and regulates its inhibitory action on insulin signaling by recruiting protein kinase Czeta. (PMID:12242277)
• catalytic domain of PKC zeta is intrinsically inactive and dependent on the transphosphorylation of the activation lo (PMID:12244101)
• the role of PKCzeta in the negative regulation of drug-induced SM-CER pathway. (PMID:12435813)
• Protein kinase C zeta-GATA-2 signaling regulates VCAM1 stimulation by thrombin in endothelial cells (PMID:12493764)
• hypoxia decreases Na,K-ATPase activity in alveolar epithelial cells by triggering its endocytosis through mitochondrial reactive oxygen species and PKC-zeta-mediated phosphorylation of the Na,K-ATPase alpha(1) subunit (PMID:12671055)
• PKC zeta has a role in the actin organization in ET-1-stimulated cells may play a role in myometrial contraction in pregnant women. (PMID:12748064)
• 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)
• PKCzeta has a role in regulating cell survival in tumor cells (PMID:12791393)
• Defective aPKC activation contributes to skeletal muscle insulin resistance in glucose intolerance and type 2 diabetes (PMID:12882907)
• enteropathogenic E coli infection of intestinal epithelial cells activates several signaling pathways including PKC zeta and ERK that lead to NF-kappa B activation, thus ensuring the proinflammatory response. (PMID:12900386)
• disregulation of the function of atypical zeta PKC might be involved in the acquisition of an invasive and metastatic phenotype in pancreatic adenocarcinoma cells. (PMID:12920244)
• PRKCZ gene may be associated with type 2 diabetes in Han population in North China. The haplotypes at five SNP sites in this gene may be responsible for this association. (PMID:12970910)
• protein kinase C iota/lambda binds to Rab 2, which inhibits aPKCiota/lambda-dependent GADPH phosphorylation [Protein kinase C lambda] (PMID:14570876)
• PKCzeta is responsible for the activation of HIF-alpha by inhibiting the mRNA expression of FIH-1 thus promoting the transcription of hypoxia-inducible genes. (PMID:14744756)
• phosphorylation of Ser(318) by PKC-zeta might contribute to the inhibitory effect of prolonged hyperinsulinemia on IRS-1 function. (PMID:15069075)
• identification of neuronal protein KIBRA as a novel substrate (PMID:15081397)
• There was expression of protein kinase C zeta in abnormal muscle fibers. Protein kinase C isoforms may play a role in the pathogenesis of myofibrillar myopathy. (PMID:15159477)
• involvement of PKC zeta in thrombin-induced permeability changes in human umbilical vein endothelial cells (PMID:15172966)
• GTPase RhoA and atypical protein kinase Czeta are required for TLR2-mediated gene transcription. (PMID:15210811)
• PKCzeta activity is regulated by nucleotide exchange factor ECT2 (PMID:15254234)
• Single nucleotide polymorphisms in protein kinase Cz (PKCZ) gene probably play a role in the susceptibility to type 2 diabetes by affecting the expression level of the relevant genes. (PMID:15285019)
• PKC-zeta, is critical to regulation of LPS-induced TLR4 lipid raft mobilization within macrophages. (PMID:15313379)
• PKCzeta could act as a modulator of nucleotide excision repair activity by regulating the expression of XPC/hHR23B heterodimer (PMID:15358551)
• The differential regulation of protein kinase C-zeta by enteropathogenic E. coli and enterohemorrhagic E. coli may in part explain the less profound effect of the latter on the barrier function of tight junctions. (PMID:15362041)
• We analyzed the dependence of the expression of some selected protein kinase C isoenzymes on the availability and/or action of androgens. (PMID:15499829)
• Disruption of the cellular environment through genetic mutation, disease, injury, or exposure to pro-oxidants, alcohol, or other insults can induce pathological PKC activation. (PMID:15544481)
• A role for PKCzeta in relaxin-mediated stimulation of cAMP was demonstrated. (PMID:15604116)
• stromal cell-derived factor 1 triggered PKC-zeta phosphorylation, translocation to the plasma membrane, and kinase activity (PMID:15630457)
• Results indicate that protein kinase C (PKC) zeta modulates hMutS alpha (MSH2, MSH6)stability and protein levels, and suggest a role for PKC zeta in genome stability by regulating mismatch repair activity. (PMID:15808853)
• Ajuba is a new cytosolic component of the IL-1 signaling pathway modulating IL-1-induced NF-kappaB activation by influencing the assembly and activity of the aPKC/p62/TRAF6 multiprotein signaling complex (PMID:15870274)
• PKCZ mediates opposing effects on Na(+)-K(+)-Exchanging ATPase activity in a breast neoplasm cell line. (PMID:15887250)
• data support the notion that PKCzeta is essential for LPS-induced NF-kB p65 subunit nuclear translocation in human myometrial cells (PMID:15935276)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkcz	ENSDARG00000043332
mus_musculus	Prkcz	ENSMUSG00000029053
rattus_norvegicus	Prkcz	ENSRNOG00000015480
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), PKN1 (ENSG00000123143), PRKCG (ENSG00000126583), PRKCA (ENSG00000154229), PKN3 (ENSG00000160447), PRKCI (ENSG00000163558), PRKCB (ENSG00000166501), PRKCE (ENSG00000171132)

Protein

Protein identifiers

Protein kinase C zeta type — Q05513 (reviewed: Q05513)

Alternative names: nPKC-zeta

All UniProt accessions (16): Q05513, D6RAN5, D6RAU1, D6RBD4, D6RC84, D6RCN4, D6RD31, D6RDM0, D6REZ8, D6RG01, D6RGG1, D6RJG4, E9PBE1, F2Z2H9, F2Z3C5, J3KRP7

UniProt curated annotations — full annotation on UniProt →

Function. Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at ‘Ser-311’. Phosphorylates VAMP2 in vitro. Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking. Involved in late synaptic long term potention phase in CA1 hippocampal cells and long term memory maintenance.

Subunit / interactions. Forms a ternary complex with SQSTM1 and KCNAB2. Forms another ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5. Interacts with PARD6A, PARD6B, PARD6G and SQSTM1. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts with ADAP1/CENTA1. Forms a ternary complex composed of SQSTM1 and PAWR. Interacts directly with SQSTM1. Interacts with IKBKB. Interacts (via the protein kinase domain) with WWC1. Forms a tripartite complex with WWC1 and DDR1, but predominantly in the absence of collagen. Component of the Par polarity complex, composed of at least phosphorylated PRKCZ, PARD3 and TIAM1. Interacts with PDPK1 (via N-terminal region). Interacts with WDFY2 (via WD repeats 1-3). Interacts with VAMP2. Forms a complex with WDFY2 and VAMP2. Interacts with APPL1. Interacts with WWC1, WWC2 and WWC3.

Subcellular location. Cytoplasm. Endosome. Cell junction. Membrane Cytoplasm.

Tissue specificity. Expressed in brain, and to a lesser extent in lung, kidney and testis.

Post-translational modifications. CDH5 is required for its phosphorylation at Thr-410. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2. Phosphorylation at Thr-410 by PI3K activates the kinase.

Activity regulation. Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator. Isoform 2: Constitutively active.

Domain organisation. The PB1 domain mediate mutually exclusive interactions with SQSTM1 and PARD6B. The C1 domain does not bind the diacylglycerol (DAG).

Miscellaneous. Produced by alternative promoter usage.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q05513-1	1	yes
Q05513-2	2, PKMzeta
Q05513-3	3

RefSeq proteins (8): NP_001028753, NP_001028754, NP_001229803, NP_001337732, NP_001337733, NP_001337734, NP_001337735, NP_002735* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000270	PB1_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
IPR012233	PKC	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR020454	DAG/PE-bd	Domain
IPR034662	aPKC_zeta	Domain
IPR034877	PB1_aPKC	Domain
IPR046349	C1-like_sf	Homologous_superfamily
IPR047314	C1_aPKC_zeta	Domain
IPR053793	PB1-like	Domain

Pfam: PF00069, PF00130, PF00433, PF00564

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 (28 total): sequence conflict 7, sequence variant 4, domain 3, modified residue 3, mutagenesis site 3, splice variant 2, binding site 2, chain 1, zinc finger region 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05513-F1	79.50	0.39

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): 376 (proton acceptor)

Ligand- & substrate-binding residues (2): 258–266; 281

Post-translational modifications (3): 560, 591, 410

Mutagenesis-validated functional residues (3):

Position	Phenotype
19	no effect on interaction with sqstm1 and pard6b.
62	loss of interaction with sqstm1 and pard6b.
66	loss of interaction with sqstm1 and pard6b.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-2173791	TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-5218921	VEGFR2 mediated cell proliferation
R-HSA-5668599	RHO GTPases Activate NADPH Oxidases
R-HSA-9634635	Estrogen-stimulated signaling through PRKCZ
R-HSA-109582	Hemostasis
R-HSA-162582	Signal Transduction
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-194138	Signaling by VEGF
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 647 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_INFLAMMATORY_RESPONSE, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN

GO Biological Process (24): microtubule cytoskeleton organization (GO:0000226), protein phosphorylation (GO:0006468), inflammatory response (GO:0006954), signal transduction (GO:0007165), establishment of cell polarity (GO:0030010), negative regulation of protein-containing complex assembly (GO:0031333), positive regulation of interleukin-10 production (GO:0032733), positive regulation of interleukin-13 production (GO:0032736), positive regulation of interleukin-4 production (GO:0032753), positive regulation of interleukin-5 production (GO:0032754), cellular response to insulin stimulus (GO:0032869), intracellular signal transduction (GO:0035556), negative regulation of apoptotic process (GO:0043066), establishment or maintenance of epithelial cell apical/basal polarity (GO:0045197), positive regulation of T-helper 2 cell differentiation (GO:0045630), negative regulation of insulin receptor signaling pathway (GO:0046627), positive regulation of insulin receptor signaling pathway (GO:0046628), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), long-term synaptic potentiation (GO:0060291), positive regulation of ERK1 and ERK2 cascade (GO:0070374), protein localization to plasma membrane (GO:0072659), neuron projection extension (GO:1990138), positive regulation of excitatory postsynaptic potential (GO:2000463), positive regulation of T-helper 2 cell cytokine production (GO:2000553)

GO Molecular Function (12): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), ATP binding (GO:0005524), zinc ion binding (GO:0008270), insulin receptor substrate binding (GO:0043560), 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 (27): nuclear envelope (GO:0005635), cytoplasm (GO:0005737), endosome (GO:0005768), centriole (GO:0005814), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), bicellular tight junction (GO:0005923), membrane (GO:0016020), apical plasma membrane (GO:0016324), nuclear matrix (GO:0016363), cell junction (GO:0030054), vesicle (GO:0031982), myelin sheath abaxonal region (GO:0035748), ciliary basal body (GO:0036064), axon hillock (GO:0043203), apical cortex (GO:0045179), extracellular exosome (GO:0070062), tight junction (GO:0070160), sperm midpiece (GO:0097225), sperm end piece (GO:0097229), PAR polarity complex (GO:0120157), nucleus (GO:0005634), microtubule organizing center (GO:0005815), cilium (GO:0005929), cell cortex (GO:0005938), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Signal Transduction	4
Platelet activation, signaling and aggregation	1
Signaling by TGF-beta Receptor Complex	1
VEGFA-VEGFR2 Pathway	1
RHO GTPase Effectors	1
Extra-nuclear estrogen signaling	1
Signaling by TGFB family members	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signaling by VEGF	1
Hemostasis	1
Signaling by Nuclear Receptors	1
ESR-mediated signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
positive regulation of cytokine production	4
intracellular anatomical structure	2
insulin receptor signaling pathway	2
regulation of insulin receptor signaling pathway	2
protein kinase activity	2
endomembrane system	2
microtubule organizing center	2
cytoskeleton organization	1
microtubule-based process	1
phosphorylation	1
protein modification process	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
establishment or maintenance of cell polarity	1
regulation of protein-containing complex assembly	1
negative regulation of cellular component organization	1
protein-containing complex assembly	1
interleukin-10 production	1
regulation of interleukin-10 production	1
interleukin-13 production	1
regulation of interleukin-13 production	1
interleukin-4 production	1
regulation of interleukin-4 production	1
interleukin-5 production	1
regulation of interleukin-5 production	1
response to insulin	1
cellular response to peptide hormone stimulus	1
signal transduction	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
establishment or maintenance of apical/basal cell polarity	1
positive regulation of immune effector process	1
positive regulation of type 2 immune response	1
T-helper 2 cell differentiation	1

Protein interactions and networks

STRING

3046 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKCZ	PARD3	Q8TEW0	992
PRKCZ	CDC42	P21181	986
PRKCZ	SQSTM1	Q13501	943
PRKCZ	PARD6A	Q9NPB6	940
PRKCZ	PARD6B	Q9BYG5	917
PRKCZ	PARD6G	Q9BYG4	883
PRKCZ	WWC1	Q8IX03	846
PRKCZ	TRAF6	Q9Y4K3	820
PRKCZ	KCNAB2	Q13303	769
PRKCZ	TJP1	Q07157	750
PRKCZ	OCLN	Q16625	741
PRKCZ	SLC39A1	Q9NY26	741
PRKCZ	RHOA	P06749	665
PRKCZ	CTNNB1	P35222	631
PRKCZ	MAP2K5	Q13163	630

IntAct

95 interactions, top by confidence:

A	B	Type	Score
RICTOR	MTOR	psi-mi:“MI:0914”(association)	0.970
PARD6B	PRKCI	psi-mi:“MI:0914”(association)	0.960
PRKCZ	PARD6B	psi-mi:“MI:0915”(physical association)	0.950
PARD6A	PRKCI	psi-mi:“MI:0914”(association)	0.950
PRKCZ	PARD6A	psi-mi:“MI:0915”(physical association)	0.910
PARD6A	PRKCZ	psi-mi:“MI:0403”(colocalization)	0.910
PARD6A	PRKCZ	psi-mi:“MI:0915”(physical association)	0.910
PRKCZ	PRKCI	psi-mi:“MI:0914”(association)	0.890
LLGL2	PRKCI	psi-mi:“MI:0914”(association)	0.890
PARD6G	PRKCZ	psi-mi:“MI:0915”(physical association)	0.890
PRKCZ	PRKCI	psi-mi:“MI:0915”(physical association)	0.890
STK24	STRN	psi-mi:“MI:0914”(association)	0.870
PRKCZ	NIPSNAP2	psi-mi:“MI:0914”(association)	0.730
PARD6G	PRKCI	psi-mi:“MI:0914”(association)	0.720
C1QBP	PRKCZ	psi-mi:“MI:0915”(physical association)	0.670
LLGL1	DNAJA2	psi-mi:“MI:0914”(association)	0.640
PRKCZ	AGER	psi-mi:“MI:0915”(physical association)	0.610
AGER	PRKCZ	psi-mi:“MI:0915”(physical association)	0.610

BioGRID (574): AKT1 (Affinity Capture-Western), AKT2 (Affinity Capture-Western), PRKCZ (Affinity Capture-Western), PRKCZ (Affinity Capture-Western), AKT1 (Biochemical Activity), PRKCZ (Affinity Capture-Western), PRKCZ (Affinity Capture-Western), PRKCZ (Two-hybrid), MAPK7 (Biochemical Activity), PRKCZ (Two-hybrid), PRKCZ (Affinity Capture-Western), C1QBP (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), DYNLL1 (Affinity Capture-MS), LLGL1 (Affinity Capture-MS)

ESM2 similar proteins: A1Z9X0, A8WUG4, A8XWC4, F1M7Y5, O13310, O19111, O74536, O97627, P00518, P07934, P09217, P13286, P23443, P26817, P26818, P26819, P31325, P34722, P35626, P41743, P54645, P54646, P67998, P67999, P83099, Q02111, Q02956, Q04759, Q05513, Q09137, Q12706, Q13131, Q16816, Q19266, Q21734, Q28948, Q2KJ16, Q3UYH7, Q5EG47, Q5R4K9

Diamond homologs: A1A4I4, A1Z7T0, A1Z9X0, A7MBL8, A8KBH6, A8WUG4, F1M7Y5, O08874, O19111, O42632, P04409, P05126, P05128, P05129, P05130, P05696, P05771, P05772, P09215, P09216, P09217, P10102, P10829, P10830, P13677, P13678, P16054, P17252, P20444, P23298, P24583, P24723, P28867, P31748, P31749, P31750, P31751, P34722, P34885, P36582

SIGNOR signaling

77 interactions.

A	Effect	B	Mechanism
PRKCZ	down-regulates	GSK3B	phosphorylation
PRKCZ	down-regulates	IRS1	phosphorylation
PRKCZ	down-regulates	MARK2	phosphorylation
PRKCZ	down-regulates	MARK3	phosphorylation
PRKCZ	up-regulates	CHAT	phosphorylation
PRKCZ	down-regulates	ADD2	phosphorylation
PRKCZ	down-regulates	CASP9	phosphorylation
PRKCZ	down-regulates	MYH10	phosphorylation
PRKCZ	up-regulates	SP1	phosphorylation
PRKCZ	up-regulates	RELA	phosphorylation
PRKCZ	“down-regulates activity”	BAX	phosphorylation
PRKCZ	“up-regulates activity”	STK11	phosphorylation
PRKCZ	up-regulates	AQP9	phosphorylation
PRKCZ	up-regulates	NR1H4	phosphorylation
PRKCZ	unknown	TRAF2	phosphorylation
PRKCZ	up-regulates	STK11	phosphorylation
PRKCZ	up-regulates	NfKb-p65/p50	phosphorylation
PRKCZ	“down-regulates quantity by destabilization”	IRS1	phosphorylation
1,2-diacyl-sn-glycerol	“up-regulates activity”	PRKCZ	binding
PRKCZ	“up-regulates activity”	AKT3	phosphorylation
PRKCZ	“up-regulates activity”	IKBKB	phosphorylation
PRKCZ	“up-regulates activity”	PSEN1	phosphorylation
PRKCZ	“down-regulates activity”	HABP4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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
Tight junction interactions	6	46.0×	1e-06
Constitutive Signaling by AKT1 E17K in Cancer	5	44.1×	1e-05
VEGFR2 mediated vascular permeability	5	42.5×	1e-05
PI3K/AKT Signaling in Cancer	5	38.4×	2e-05
Signaling by ERBB2	5	36.0×	2e-05
Programmed Cell Death	7	21.4×	8e-06
Extra-nuclear estrogen signaling	6	21.3×	2e-05
Apoptosis	6	21.0×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	7	75.3×	3e-09
establishment of cell polarity	5	35.5×	8e-05
obsolete positive regulation of NF-kappaB transcription factor activity	5	19.0×	1e-03
axonogenesis	5	14.9×	2e-03
negative regulation of apoptotic process	11	7.1×	8e-05
intracellular signal transduction	9	6.3×	1e-03
inflammatory response	8	5.6×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	6
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
394133	GRCh37/hg19 1p36.33(chr1:1538143-2140271)x1	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3960 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:2150857:T:C	F252S	1.000
1:2150872:T:A	V257D	1.000
1:2150875:T:A	I258N	1.000
1:2150877:G:A	G259R	1.000
1:2150877:G:C	G259R	1.000
1:2150877:G:T	G259W	1.000
1:2150878:G:A	G259E	1.000
1:2150878:G:C	G259A	1.000
1:2150878:G:T	G259V	1.000
1:2150880:C:A	R260S	1.000
1:2150881:G:C	R260P	1.000
1:2150883:G:A	G261R	1.000
1:2150883:G:C	G261R	1.000
1:2150883:G:T	G261W	1.000
1:2150884:G:A	G261E	1.000
1:2150884:G:C	G261A	1.000
1:2150884:G:T	G261V	1.000
1:2150886:A:C	S262R	1.000
1:2150888:C:A	S262R	1.000
1:2150888:C:G	S262R	1.000
1:2150892:G:C	A264P	1.000
1:2150893:C:A	A264D	1.000
1:2150893:C:T	A264V	1.000
1:2150895:A:G	K265E	1.000
1:2150897:G:C	K265N	1.000
1:2150897:G:T	K265N	1.000
1:2150898:G:C	V266L	1.000
1:2150899:T:C	V266A	1.000
1:2150902:T:C	L267P	1.000
1:2150905:T:C	L268P	1.000

dbSNP variants (sampled 300 via entrez): RS1000019726 (1:2106661 C>T), RS1000021623 (1:2050282 G>A), RS1000027574 (1:2077208 G>A), RS1000036283 (1:2148636 T>G), RS1000038391 (1:2087920 G>T), RS1000046125 (1:2059501 C>T), RS1000047028 (1:2127904 C>T), RS1000067811 (1:2168297 G>A), RS1000072310 (1:2077388 A>G), RS1000096076 (1:2180374 C>T), RS1000120685 (1:2085495 A>C,G), RS1000122507 (1:2116028 T>C), RS1000141506 (1:2163916 A>T), RS1000177095 (1:2151049 C>T), RS1000207669 (1:2147100 A>G,T)

Disease associations

OMIM: gene MIM:176982 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

99 total (30 of 99 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000055	Abnormal female external genitalia morphology
HP:0000077	Abnormality of the kidney
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000160	Narrow mouth
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000270	Delayed cranial suture closure
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000457	Depressed nasal ridge
HP:0000464	Abnormality of the neck
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000708	Atypical behavior
HP:0000717	Autism

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000817_140	Height	2.000000e-08
GCST000885_3	Response to antipsychotic treatment in schizophrenia (reasoning)	1.000000e-06
GCST005951_34	Body mass index	3.000000e-08
GCST005951_35	Body mass index	4.000000e-08
GCST007325_194	General risk tolerance (MTAG)	2.000000e-08
GCST010696_20	Cortical thickness (min-P)	2.000000e-10
GCST010697_42	Cortical surface area (min-P)	4.000000e-20
GCST010698_65	Subcortical volume (min-P)	2.000000e-17
GCST010699_76	Brain morphology (min-P)	3.000000e-17
GCST010700_27	Cortical thickness (MOSTest)	7.000000e-44
GCST010701_61	Cortical surface area (MOSTest)	1.000000e-14
GCST010702_167	Subcortical volume (MOSTest)	4.000000e-18
GCST010703_38	Brain morphology (MOSTest)	9.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004350	reasoning
EFO:0004340	body mass index
EFO:0008579	risk-taking behaviour
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL3438 (SINGLE PROTEIN), CHEMBL3885627 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 284,360 (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
CHEMBL265502	SURAMIN	3	36,848
CHEMBL38380	FASUDIL	3	11,953
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2	1,362
CHEMBL28509	EDELFOSINE	2	10,540
CHEMBL3137336	UPROSERTIB	2	1,624
CHEMBL574737	UCN-01	2	2,217
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980715	LAUROGUADINE	2	294
CHEMBL2107832	PIMASERTIB	2	3,452
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL572878	TOZASERTIB	2	2,998

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Iota subfamily

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 3 [PMID: 19097791]	Inhibition	8.65	pIC50
Gö 6983	Inhibition	7.22	pIC50
balanol	Inhibition	5.23	pIC50

Binding affinities (BindingDB)

78 measured of 107 human assays (108 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
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
CHEMBL4587471	IC50	0.36 nM
CHEMBL4575056	EC50	0.6 nM
(3R,4R)-3-methoxy-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	IC50	3.93 nM	US-10189849: CDK inhibitors
indazole-benzimidazole, 3	IC50	4.1 nM
indazole-benzimidazole, 4	IC50	13.3 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
6-{5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]pyridin-3-yl}isoquinolin-3-amine	IC50	31 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-[({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-({[(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
indazole-benzimidazole, 1	IC50	102 nM
indazole-benzimidazole, 12	IC50	247 nM
6-{5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]-2-ethynylpyridin-3-yl}isoquinoline	IC50	260 nM
13a (S-)	IC50	270 nM
2-{[2,6-dihydroxy-4-({[(1R,2R)-2-[(4-hydroxybenzene)amido]cycloheptyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	270 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-({[(4S)-3-[(4-hydroxybenzene)amido]-1-azabicyclo[3.2.2]nonan-4-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	415 nM
6-{5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]-2-chloropyridin-3-yl}isoquinoline	IC50	540 nM
ethyl 2-amino-4-[4-(dimethylamino)phenyl]thiophene-3-carboxylate	IC50	1000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
indazole-benzimidazole, 9	IC50	1040 nM
indazole-benzimidazole, 24	IC50	1070 nM
3-[(2S)-2-amino-3-({5-[(E)-2-(pyridin-4-yl)ethenyl]pyridin-3-yl}oxy)propyl]-1H-indole	IC50	1200 nM
indazole-benzimidazole, 16	IC50	1310 nM
indazole-benzimidazole, 11	IC50	1730 nM
ethyl 2-amino-4-(4-aminophenyl)thiophene-3-carboxylate	IC50	2000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
ethyl 2-amino-4-(1,3-benzodioxol-5-yl)thiophene-3-carboxylate	IC50	2000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
2-{[2,6-dihydroxy-4-({[(8S,9R)-9-[(4-hydroxybenzene)amido]tricyclo[5.2.1.0^{2,6}]decan-8-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	2700 nM
[2-amino-4-(3,4-dichlorophenyl)thiophen-3-yl]-morpholin-4-ylmethanone	IC50	3000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
indazole-benzimidazole, 25	IC50	3020 nM
ethyl 2-amino-4-(2-fluoro-4-methoxyphenyl)thiophene-3-carboxylate	IC50	4000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
[2-amino-4-(3,4-dimethoxyphenyl)thiophen-3-yl]-morpholin-4-ylmethanone	IC50	4000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
2-amino-4-(3,4-dimethoxyphenyl)-N-ethylthiophene-3-carboxamide	IC50	4000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
(3-methoxyphenyl)methyl 2-amino-4-(3,4-dimethoxyphenyl)thiophene-3-carboxylate	IC50	5000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
2-amino-4-(3,4-dichlorophenyl)-N-propan-2-ylthiophene-3-carboxamide	IC50	5000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
2-amino-4-(3,4-dichlorophenyl)-N-ethylthiophene-3-carboxamide	IC50	5000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
2-{[2,6-dihydroxy-4-({[(3R,4R)-3-[(4-hydroxybenzene)amido]piperidin-4-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid	IC50	5100 nM
ethyl 4-(4-acetamidophenyl)-2-aminothiophene-3-carboxylate	IC50	6000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
(3-methoxyphenyl)methyl 2-amino-4-(4-carbamoylphenyl)thiophene-3-carboxylate	IC50	6000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
benzyl 2-amino-4-(3,4-dimethoxyphenyl)thiophene-3-carboxylate	IC50	6000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
indazole-benzimidazole, 10	IC50	6100 nM
2-amino-4-(3,4-dimethoxyphenyl)thiophene-3-carbonitrile	IC50	7000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
(2-fluorophenyl)methyl 2-amino-4-(3,4-dimethoxyphenyl)thiophene-3-carboxylate	IC50	7000 nM	US-8889672: Compounds, formulations, and methods of protein kinase C inhibition
indazole-benzimidazole, 21	IC50	8930 nM
indazole-benzimidazole, 6	IC50	10000 nM

ChEMBL bioactivities

506 potent at pChembl≥5 of 677 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	IC50	0.1	nM	CHEMBL4635482
9.89	IC50	0.13	nM	CHEMBL3741746
9.85	IC50	0.14	nM	CHEMBL4575056
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	0.2	nM	CHEMBL4636488
9.66	IC50	0.22	nM	CHEMBL4435580
9.44	IC50	0.36	nM	CHEMBL4587471
9.30	IC50	0.5	nM	CHEMBL4646995
9.26	EC50	0.55	nM	CHEMBL4587471
9.22	EC50	0.6	nM	CHEMBL4575056
9.22	IC50	0.6	nM	CHEMBL4644939
9.22	IC50	0.6	nM	STAUROSPORINE
9.10	IC50	0.8	nM	CHEMBL4636337
9.05	IC50	0.9	nM	CHEMBL4632523
9.00	EC50	1	nM	CHEMBL2393448
9.00	EC50	1	nM	CHEMBL2393447
9.00	EC50	1	nM	CHEMBL2393431
9.00	IC50	1	nM	STAUROSPORINE
8.96	IC50	1.1	nM	CHEMBL4643553
8.85	IC50	1.4	nM	CHEMBL4642166
8.85	IC50	1.4	nM	CHEMBL4637452
8.77	IC50	1.7	nM	CHEMBL291126
8.70	IC50	2	nM	CHEMBL162621
8.70	IC50	2	nM	STAUROSPORINE
8.70	EC50	2	nM	CHEMBL2393450
8.70	EC50	2	nM	CHEMBL2393427
8.66	IC50	2.2	nM	CHEMBL83790
8.65	IC50	2.26	nM	CHEMBL514197
8.57	IC50	2.7	nM	STAUROSPORINE
8.52	IC50	3	nM	STAUROSPORINE
8.52	EC50	3	nM	CHEMBL200027
8.52	EC50	3	nM	CHEMBL2393423
8.47	IC50	3.4	nM	CHEMBL4647780
8.39	IC50	4.1	nM	UCN-01
8.39	IC50	4.1	nM	CHEMBL4643470
8.30	IC50	5	nM	CHEMBL538718
8.29	IC50	5.18	nM	CHEMBL480391
8.28	Ki	5.3	nM	BALANOL
8.25	IC50	5.6	nM	CHEMBL473631
8.22	Kd	6	nM	CHEMBL27768
8.22	IC50	6	nM	STAUROSPORINE
8.19	IC50	6.4	nM	CHEMBL4641918
8.19	IC50	6.5	nM	STAUROSPORINE
8.15	IC50	7	nM	STAUROSPORINE
8.12	IC50	7.5	nM	STAUROSPORINE

PubChem BioAssay actives

327 with measured affinity, of 2581 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
7-(4-amino-2-fluorophenyl)-N-[(3S)-azepan-3-yl]isoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	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
7-phenyl-N-[(3S)-piperidin-3-yl]isoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	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] 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
7-(4-aminophenyl)-N-piperidin-3-ylisoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0005	uM
4-[5-(piperidin-3-ylamino)isoquinolin-7-yl]phenol	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0006	uM
7-(4-amino-2,3-difluorophenyl)-N-[(3S)-azepan-3-yl]isoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0008	uM
7-(6-amino-3-pyridinyl)-N-[(3S)-azepan-3-yl]isoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0009	uM
ethyl 2-amino-4-(4-aminophenyl)thiophene-3-carboxylate	752123: Inhibition of atypical PKCzeta in HEK293 cells assessed as TNF-induced NFkappaB activation incubated for 3 hrs prior to TNF induction measured after 5 hrs by bright-glo luciferase reporter gene assay	ec50	0.0010	uM
ethyl 2-amino-4-[4-(dimethylamino)phenyl]thiophene-3-carboxylate	752123: Inhibition of atypical PKCzeta in HEK293 cells assessed as TNF-induced NFkappaB activation incubated for 3 hrs prior to TNF induction measured after 5 hrs by bright-glo luciferase reporter gene assay	ec50	0.0010	uM
(3-methoxyphenyl)methyl 2-amino-4-(3,4-dimethoxyphenyl)thiophene-3-carboxylate	752123: Inhibition of atypical PKCzeta in HEK293 cells assessed as TNF-induced NFkappaB activation incubated for 3 hrs prior to TNF induction measured after 5 hrs by bright-glo luciferase reporter gene assay	ec50	0.0010	uM
7-(6-amino-2-fluoro-3-pyridinyl)-N-[(3S)-azepan-3-yl]isoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0011	uM
7-(4-amino-2,5-difluorophenyl)-N-[(3S)-azepan-3-yl]isoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0014	uM
7-(4-aminophenyl)-N-[(3S)-azepan-3-yl]isoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0014	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
ethyl 2-amino-4-(1,3-benzodioxol-5-yl)thiophene-3-carboxylate	752123: Inhibition of atypical PKCzeta in HEK293 cells assessed as TNF-induced NFkappaB activation incubated for 3 hrs prior to TNF induction measured after 5 hrs by bright-glo luciferase reporter gene assay	ec50	0.0020	uM
benzyl 2-amino-4-(3,4-dimethoxyphenyl)thiophene-3-carboxylate	752123: Inhibition of atypical PKCzeta in HEK293 cells assessed as TNF-induced NFkappaB activation incubated for 3 hrs prior to TNF induction measured after 5 hrs by bright-glo luciferase reporter gene assay	ec50	0.0020	uM
2-methoxy-4-[3-[4-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-indazol-6-yl]phenol	1799297: PKC Enzyme Assay from Article 10.1016/j.bmcl.2008.11.105: “2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: design and synthesis of a potent and isoform selective PKC-zeta inhibitor.”	ic50	0.0023	uM
propan-2-yl 2-amino-4-(3,4-dimethoxyphenyl)thiophene-3-carboxylate	752123: Inhibition of atypical PKCzeta in HEK293 cells assessed as TNF-induced NFkappaB activation incubated for 3 hrs prior to TNF induction measured after 5 hrs by bright-glo luciferase reporter gene assay	ec50	0.0030	uM
[4-[[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	752123: Inhibition of atypical PKCzeta in HEK293 cells assessed as TNF-induced NFkappaB activation incubated for 3 hrs prior to TNF induction measured after 5 hrs by bright-glo luciferase reporter gene assay	ec50	0.0030	uM
7-(6-amino-4-fluoro-3-pyridinyl)-N-[(3S)-azepan-3-yl]isoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0034	uM
N’-(7-phenylisoquinolin-5-yl)ethane-1,2-diamine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0041	uM
4-[3-[4-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-indazol-6-yl]aniline	1799297: PKC Enzyme Assay from Article 10.1016/j.bmcl.2008.11.105: “2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: design and synthesis of a potent and isoform selective PKC-zeta inhibitor.”	ic50	0.0052	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
4-[3-[4-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-indazol-6-yl]phenol	1799297: PKC Enzyme Assay from Article 10.1016/j.bmcl.2008.11.105: “2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: design and synthesis of a potent and isoform selective PKC-zeta inhibitor.”	ic50	0.0056	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	2150891: Binding affinity to PKC (unknown origin) assessed as dissociation constant	kd	0.0060	uM
7-phenyl-N-piperidin-3-ylisoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0064	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	1459482: Activation of PKC in human platelet assessed as induction of platelet aggregation measured within 15 mins by tribidimetric method	ec50	0.0095	uM
N-[(3S)-azepan-3-yl]-7-phenylisoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0097	uM
1-(6-methoxy-2,3-dihydro-1H-isoindol-5-yl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzimidazole	1375387: Inhibition of full-length N-terminal GST-fused human PKC-zeta expressed in baculovirus expression system using (5FAM) RFARKGSLRQKNV as substrate after 60 mins by caliper assay	ic50	0.0100	uM
ethyl 2-amino-4-(2-fluoro-4-methoxyphenyl)thiophene-3-carboxylate	752123: Inhibition of atypical PKCzeta in HEK293 cells assessed as TNF-induced NFkappaB activation incubated for 3 hrs prior to TNF induction measured after 5 hrs by bright-glo luciferase reporter gene assay	ec50	0.0100	uM
4-piperazin-1-yl-2-pyridin-4-yl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine	1662458: Inhibition of recombinant full-length human aPKCzeta expressed in Sf21 insect cells using 5FAM-ERMRPRKRQGSVRRRV-NH2 as substrate in presence of ATP after 60 mins by IMAP fluorescence polarization analysis	ic50	0.0120	uM
N-[4-[5-(piperidin-3-ylamino)isoquinolin-7-yl]phenyl]acetamide	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0130	uM
6-[(3S)-pyrrolidin-3-yl]oxy-4-(1H-pyrrolo[2,3-b]pyridin-5-yl)isoquinoline	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0130	uM
N-[(3S)-azepan-3-yl]-7-(2,6-difluorophenyl)isoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0152	uM
5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)-N-[(3S,4S,6S)-4-(3,4-difluorophenyl)-6-(2-hydroxyethyl)piperidin-3-yl]furan-2-carboxamide	1608042: Inhibition of PKC (unknown origin)	ic50	0.0160	uM
3-methoxy-4-[3-[4-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-indazol-6-yl]phenol	1799297: PKC Enzyme Assay from Article 10.1016/j.bmcl.2008.11.105: “2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: design and synthesis of a potent and isoform selective PKC-zeta inhibitor.”	ic50	0.0220	uM
3-methoxy-4-[3-[4-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-indazol-6-yl]aniline	1799297: PKC Enzyme Assay from Article 10.1016/j.bmcl.2008.11.105: “2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: design and synthesis of a potent and isoform selective PKC-zeta inhibitor.”	ic50	0.0233	uM
(2S,5S)-9-decyl-5-(hydroxymethyl)-1-methyl-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-3-one	2163933: Activation of PKC in human ACH-2 cells infected with latent HIV-1 assessed as reversal of HIV-1 latency by measuring increase in p24 antigen level incubated for 48 hrs by chemiluminescent enzyme immunoassay	ec50	0.0250	uM
4-[6-[(3S)-pyrrolidin-3-yl]oxyisoquinolin-4-yl]aniline	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0330	uM
4-[[[6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl]amino]methyl]phenol	1180278: Inhibition of PKC (unknown origin) using C1 peptide substrate	ic50	0.0350	uM
7-phenyl-N-[(3R)-piperidin-3-yl]isoquinolin-5-amine	1658843: Inhibition of recombinant human PKCzeta using biotin-KKKKRFSFKKSFK substrate and ATP incubated for 30 mins by TR-FRET method	ic50	0.0350	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637128: Inhibition of full-length recombinant human PRKCZ expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases expression, increases methylation	4
Benzo(a)pyrene	affects methylation, decreases expression	3
Valproic Acid	increases expression, increases methylation, affects expression	3
sodium arsenite	decreases expression, increases expression	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects localization, decreases phosphorylation	2
Tetradecanoylphorbol Acetate	affects localization, increases expression	2
Cyclosporine	increases expression, decreases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	increases methylation, decreases methylation, affects cotreatment	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
trichostatin A	affects expression, decreases reaction	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
afimoxifene	decreases response to substance	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
dibenzo(a,l)pyrene	decreases expression	1
beta-methylcholine	affects expression	1
phenethyl isothiocyanate	decreases expression, decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	affects localization	1
(N)-methanocarba-2MeSADP	decreases reaction, increases activity, increases phosphorylation	1
bisphenol S	decreases methylation	1
jinfukang	increases expression, increases reaction	1
PF 3758309	increases expression	1
Temozolomide	increases expression	1

ChEMBL screening assays

638 unique, capped per target: 626 binding, 10 functional, 2 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
CHEMBL4407592	ADMET	Inhibition of recombinant human full-length untagged PRKCZ expressed in baculovirus expression system at 25 uM using FRET-labeled Ser/Thr 07 peptide as substrate measured after 1 hr by Z’-lyte assay relative to control	Optimization and Mechanistic Characterization of Pyridopyrimidine Inhibitors of Bacterial Biotin Carboxylase. — J Med Chem

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3EX	Abcam HEK293T PRKCZ KO 1	Transformed cell line	Female
CVCL_B3EY	Abcam HEK293T PRKCZ KO 2	Transformed cell line	Female
CVCL_D7YL	Ubigene A-549 PRKCZ KO	Cancer cell line	Male
CVCL_D8U0	Ubigene HCT 116 PRKCZ KO	Cancer cell line	Male
CVCL_D9PQ	Ubigene HEK293 PRKCZ KO	Transformed cell line	Female
CVCL_E0LY	Ubigene HeLa PRKCZ KO	Cancer cell line	Female
CVCL_TG93	HAP1 PRKCZ (-) 1	Cancer cell line	Male
CVCL_TG94	HAP1 PRKCZ (-) 2	Cancer cell line	Male
CVCL_TG95	HAP1 PRKCZ (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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