PRKCQ

Summary

PRKCQ (protein kinase C theta, HGNC:9410) is a protein-coding gene on chromosome 10p15.1, encoding Protein kinase C theta type (Q04759). Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of m….

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. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipid-dependent protein kinase. This kinase is important for T-cell activation. It is required for the activation of the transcription factors NF-kappaB and AP-1, and may link the T cell receptor (TCR) signaling complex to the activation of the transcription factors.

Source: NCBI Gene 5588 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 102 total
• Druggable target: yes — 37 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006257

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9410
Approved symbol	PRKCQ
Name	protein kinase C theta
Location	10p15.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000065675
Ensembl biotype	protein_coding
OMIM	600448
Entrez	5588

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 16 protein_coding

ENST00000263125, ENST00000397176, ENST00000539722, ENST00000866196, ENST00000866197, ENST00000866198, ENST00000866199, ENST00000915285, ENST00000915286, ENST00000915287, ENST00000915288, ENST00000955424, ENST00000955425, ENST00000955426, ENST00000955427, ENST00000955428

RefSeq mRNA: 7 — MANE Select: NM_006257 NM_001242413, NM_001282644, NM_001282645, NM_001323265, NM_001323266, NM_001323267, NM_006257

CCDS: CCDS55701, CCDS60482, CCDS7079

Canonical transcript exons

ENST00000263125 — 18 exons

Exon	Start	End
ENSE00000464823	6486035	6486144
ENSE00000689349	6430810	6430938
ENSE00000689350	6441893	6442081
ENSE00000689351	6456674	6456812
ENSE00000689352	6462303	6462365
ENSE00000689354	6464313	6464404
ENSE00000689355	6478992	6479165
ENSE00000689356	6483440	6483600
ENSE00000689357	6485152	6485269
ENSE00000689358	6491683	6491812
ENSE00000689359	6497035	6497120
ENSE00000689360	6497220	6497251
ENSE00000689362	6507436	6507496
ENSE00000837256	6498396	6498558
ENSE00003603466	6510995	6511194
ENSE00003648839	6515018	6515144
ENSE00003889853	6427148	6428362
ENSE00003895023	6580211	6580276

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 98.10.

FANTOM5 (CAGE): breadth broad, TPM avg 4.1279 / max 129.6997, expressed in 606 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108161	2.9147	493
108164	0.9054	342
108160	0.1730	26
108162	0.0893	53
108163	0.0300	5
108159	0.0155	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
triceps brachii	UBERON:0001509	98.10	gold quality
gluteal muscle	UBERON:0002000	97.75	gold quality
biceps brachii	UBERON:0001507	97.69	gold quality
vastus lateralis	UBERON:0001379	97.59	gold quality
quadriceps femoris	UBERON:0001377	97.38	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.29	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.23	gold quality
skeletal muscle tissue	UBERON:0001134	96.22	gold quality
diaphragm	UBERON:0001103	95.82	gold quality
deltoid	UBERON:0001476	95.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.82	gold quality
tibialis anterior	UBERON:0001385	94.03	gold quality
muscle organ	UBERON:0001630	93.71	gold quality
gastrocnemius	UBERON:0001388	93.27	gold quality
muscle of leg	UBERON:0001383	92.42	gold quality
pigmented layer of retina	UBERON:0001782	91.85	gold quality
muscle tissue	UBERON:0002385	90.93	gold quality
body of tongue	UBERON:0011876	89.38	gold quality
granulocyte	CL:0000094	89.02	gold quality
thymus	UBERON:0002370	86.61	gold quality
blood	UBERON:0000178	84.13	gold quality
buccal mucosa cell	CL:0002336	83.29	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.10	gold quality
type B pancreatic cell	CL:0000169	81.29	gold quality
olfactory bulb	UBERON:0002264	81.25	gold quality
tongue	UBERON:0001723	80.50	gold quality
corpus callosum	UBERON:0002336	80.44	gold quality
thyroid gland	UBERON:0002046	80.43	gold quality
lymph node	UBERON:0000029	80.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	855.49
E-ANND-3	yes	8.00
E-MTAB-6379	no	652.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ITGB1	Activation

Upstream regulators (CollecTRI, top): AP1, EBF1, HAND1, HAND2, JUND, MYC, NFKB, PDGFB, RUNX1, SSRP1, STAT3, STAT4, STAT6

miRNA regulators (miRDB)

54 targeting PRKCQ, 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-4776-3P	100.00	68.73	1340
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-6809-5P	99.13	68.45	1223

Literature-anchored findings (GeneRIF, showing 40)

• Rac1, Rac2 and Mtl, have overlapping functions in the control of epithelial morphogenesis, myoblast fusion, and axon growth and guidance (PMID:11919634)
• axon growth, guidance and branching could be controlled by differential activation of Rac signalling pathways (PMID:11919635)
• Interaction of Bruton’s tyrosine kinase and protein kinase Ctheta in platelets (PMID:11788586)
• Translocation of PKC[theta] in T cells is mediated by a nonconventional, PI3-K- and Vav-dependent pathway, but does not absolutely require phospholipase C (PMID:11956228)
• PKC theta functions as a positive modulator of calcineurin-regulated retinoid X receptor responsive element-dependent transcription during T cell activation. (PMID:12097375)
• PKC theta is rapidly and persistently activated in gamma delta T cells by the mycobacterial phosphoantigen isopentenyl pyrophosphate, as determined by evidence of translocation and phosphorylation. (PMID:12421956)
• T cell activation silences nuclear receptor-dependent transactivation in part through PKC theta-dependent enhancement of silencing mediator of retinoic acid and thyroid hormone receptors (SMRT)-receptor interaction. (PMID:12890684)
• documented the first deficiency of a human PKC isozyme (PKC-), suggesting a major role of this isozyme in platelet production and function (PMID:14525764)
• Required for changes in cytoskeletal assembly and barrier permeability in intestinal monolayers. Involves changes in phosphorylation and/or assembly of cytoskeleton. Ability to alter cytoskeletal and barrier dynamics. (PMID:14985240)
• contribution of two lipid pools to PLC-dependent Ras activation in response to TCR triggering (PMID:15064353)
• PKC-theta is an interferon-inducible kinase that plays an important role in the generation of interferon-responses in T-cells (PMID:15150272)
• protein kinase C alpha, iota, and theta binding to L-selectin cytoplasmic domain is modulated by receptor phosphorylation (PMID:15192100)
• PKC-theta may have a role in development of gastrointestinal stromal tumors (PMID:15217944)
• Increased Protein Kinase C theta expression and constitutive activation is associated with gastrointestinal stromal tumors (PMID:15289315)
• PKCtheta has been shown to be required for T-cell IL-2 production (PMID:15358536)
• Data suggest that PKCtheta plays a critical role in the co-stimulatory functions of CD43 in human T cells. (PMID:15522211)
• PKC theta mediates the activation of NF-kappa B by pre-TCR in immature thymocytes and contributes to the development of Notch3-dependent T-cell lymphoma. (PMID:15592506)
• increased translocation from the cytoplasm to the membrane of protein kinase theta, a T cell signaling molecule that colocalizes with the TCR within the supramolecular activation cluster (PMID:15749850)
• Using a panel of phospho-specific antibodies, we have determined that PKC beta(I) and delta are constitutively phosphorylated on all three sites in unstimulated and activated T cells. (PMID:16009340)
• In CD8+ T cells from TCR-transgenic mice crossed to protein kinase C-theta PKCtheta-deficient mice, PKCtheta is not required for CD8+ T cell proliferation but is important for T cell survival and differentiation into functional CTLs (PMID:16210616)
• Data suggest that autophosphorylation of protein kinase Ctheta at Thr-219 plays an important role in the correct targeting and cellular function of PKCtheta upon antigen receptor ligation. (PMID:16252004)
• Menin’s dynamic regulation of histone modifiers with JunD is responsible for PKC theta-synergistic effect on Nur77 expression in T cell (PMID:16264271)
• PKC-theta can both positively and negatively regulate the Ca2+ influx that is critical for NFAT activity. (PMID:16309697)
• T cell receptor/CD28-induced recruitment of PKC theta to specific sites such as the T cell-antigen-presenting-cell (APC) contact area represents a critical mechanism that regulates the unique functions of PKC theta and its access to substrates in T cells. (PMID:16849481)
• Results demonstrate that protein kinase Ctheta-dependent reactive oxygen species generation by mitochondrial complex I is essential for activation-induced T-cell death. (PMID:17339328)
• PKC has a unique membrane binding and activation mechanism that may account for its subcellular targeting properties (PMID:17548359)
• These data demonstrate that atypical PKCzeta/iota isotypes serve as direct downstream targets of PKCtheta in the signalling pathway leading to NF-kappaB activation in T lymphocytes. (PMID:17588663)
• TCL1 inhibits activation-induced cell death in T cells by blocking PKCtheta and ERK activation, upon cellular activation (PMID:17846228)
• study concludes that the activation of novel protein kinase Cs, PKC delta and theta, by Nef is required to increase viral replication/infectivity and direct the subcellular localization of Nef (PMID:17904606)
• activation of PKCtheta inhibits the FOXO3a/ERalpha/p27(Kip1) axis that normally maintains an epithelial cell phenotype and induces c-Rel target genes, thereby promoting proliferation, survival, and more invasive breast cancer. (PMID:18037997)
• PKC theta activation induces insulin-mediated vasoconstriction by inhibition of Akt and stimulation of ERK1/2 in muscle resistance arteries. (PMID:18086904)
• Moraxella catarrhalis infection activates protein kinase C and its isoforms alpha, epsilon and theta, which differentially regulate interleukin-8 transcription in human pulmonary epithelial cells. (PMID:18184679)
• Overexpression of an active form of protein kinase C-theta reverts A238L-mediated inhibition of the transcriptional activity of coactivator p300. (PMID:18250452)
• Protein kinase C-theta regulates KIT expression and proliferation in gastrointestinal stromal tumors. (PMID:18521081)
• PKC-tetha sets the threshold for T-cell activation by positively regulating both the cytokine responses and the adhesive capacities of T lymphocytes. (PMID:18796635)
• Formation of a stable peripheral activation cluster of the immunological synapse is partially controlled by protein kinase C theta, confines released lytic molecules at the synaptic interface and enhances the effectiveness of target cell lysis. (PMID:18802085)
• In the T cell-dendritic cell synapse, transgenic murine CD80 clusters are colocalized with CD28 and protein kinase C theta, a characteristic of the central supramolecular activation cluster. (PMID:18802089)
• Protein kinase C theta is a downstream effector of lymphocyte specific protein tyrosine kinase p56 (Lck) and cooperatively promotes HIV transcription. (PMID:19050260)
• PKC-theta isoform plays a significant role in platelet functional responses downstream of PAR and GPVI receptors. (PMID:19164598)
• Reduced expression of PKCtheta is well correlated with the grade of human hepatocellular carcinoma cancer cells (PMID:19949911)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkcq	ENSDARG00000034173
mus_musculus	Prkcq	ENSMUSG00000026778
rattus_norvegicus	Prkcq	ENSRNOG00000019057

Paralogs (5): AKT2 (ENSG00000105221), AKT3 (ENSG00000117020), PDPK1 (ENSG00000140992), AKT1 (ENSG00000142208), PRKCD (ENSG00000163932)

Protein

Protein identifiers

Protein kinase C theta type — Q04759 (reviewed: Q04759)

Alternative names: nPKC-theta

All UniProt accessions (1): Q04759

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in ‘outside-in’ signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at ‘Ser-504’ and ‘Ser-532’ and negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylates CCDC88A/GIV and inhibits its guanine nucleotide exchange factor activity. Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking.

Subunit / interactions. Part of a lipid raft complex composed at least of BCL10, CARD11, MALT1 and IKBKB. Interacts with GLRX3 (via N-terminus). Interacts with ECT2. Interacts with CCDC88A/GIV; the interaction leads to phosphorylation of CCDC88A and inhibition of its guanine nucleotide exchange factor activity. Interacts with PRKCH upstream open reading frame 2; the interaction leads to inhibition of kinase activity. Interacts with CD28.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Expressed in skeletal muscle, T-cells, megakaryoblastic cells and platelets.

Post-translational modifications. Autophosphorylation at Thr-219 is required for targeting to the TCR and cellular function of PRKCQ upon antigen receptor ligation. Following TCR stimulation, phosphorylated at Tyr-90 and Ser-685.

Activity regulation. Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-538 (activation loop of the kinase domain), Ser-676 (turn motif) and Ser-695 (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.

Isoforms (3)

UniProt ID	Names	Canonical?
Q04759-1	1	yes
Q04759-2	2
Q04759-3	3

RefSeq proteins (7): NP_001229342, NP_001269573, NP_001269574, NP_001310194, NP_001310195, NP_001310196, NP_006248* (*=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
IPR027264	PKC_theta	Family
IPR034668	nPKC_theta	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF00069, PF00130, PF00433, PF21494

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 (82 total): strand 27, helix 20, modified residue 7, mutagenesis site 7, turn 5, sequence variant 4, domain 3, splice variant 2, zinc finger region 2, binding site 2, chain 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
1XJD	X-RAY DIFFRACTION	2
5F9E	X-RAY DIFFRACTION	2
2JED	X-RAY DIFFRACTION	2.32
4Q9Z	X-RAY DIFFRACTION	2.6
4RA5	X-RAY DIFFRACTION	2.61
2ENJ	SOLUTION NMR
2ENN	SOLUTION NMR
2ENZ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04759-F1	80.20	0.45

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): 504 (proton acceptor)

Ligand- & substrate-binding residues (2): 386–394; 409

Post-translational modifications (7): 219, 348, 538, 676, 685, 695, 90

Mutagenesis-validated functional residues (7):

Position	Phenotype
90	loss of function in t-cells proliferation. no effect on kinase activity.
148	constitutively active form.
219	loss of transactivation of the il2 promoter and translocation to the plasma membrane. no effect on kinase activity.
409	loss of kinase activity.
538	loss of kinase activity.
676	reduction in kinase activity.
695	reduction in kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

36 pathways

ID	Pathway
R-HSA-111465	Apoptotic cleavage of cellular proteins
R-HSA-114508	Effects of PIP2 hydrolysis
R-HSA-202424	Downstream TCR signaling
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-373752	Netrin-1 signaling
R-HSA-418597	G alpha (z) signalling events
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-9648002	RAS processing
R-HSA-109581	Apoptosis
R-HSA-109582	Hemostasis
R-HSA-1266738	Developmental Biology
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-202403	TCR signaling
R-HSA-212436	Generic Transcription Pathway
R-HSA-2187338	Visual phototransduction
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling
R-HSA-2514856	The phototransduction cascade
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-416476	G alpha (q) signalling events
R-HSA-422475	Axon guidance
R-HSA-5357801	Programmed Cell Death
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-5683057	MAPK family signaling cascades
R-HSA-5684996	MAPK1/MAPK3 signaling
R-HSA-73857	RNA Polymerase II Transcription

MSigDB gene sets: 401 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_CELL_CHEMOTAXIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS

GO Biological Process (26): regulation of cell growth (GO:0001558), regulation of DNA-templated transcription (GO:0006355), membrane protein ectodomain proteolysis (GO:0006509), inflammatory response (GO:0006954), axon guidance (GO:0007411), positive regulation of telomere maintenance (GO:0032206), positive regulation of interleukin-17 production (GO:0032740), positive regulation of interleukin-2 production (GO:0032743), positive regulation of interleukin-4 production (GO:0032753), intracellular signal transduction (GO:0035556), CD4-positive, alpha-beta T cell proliferation (GO:0035739), Fc-epsilon receptor signaling pathway (GO:0038095), negative regulation of insulin receptor signaling pathway (GO:0046627), positive regulation of T cell activation (GO:0050870), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), cell chemotaxis (GO:0060326), negative regulation of T cell apoptotic process (GO:0070233), regulation of platelet aggregation (GO:0090330), positive regulation of T-helper 17 type immune response (GO:2000318), positive regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000563), positive regulation of T-helper 2 cell activation (GO:2000570), immune system process (GO:0002376), protein phosphorylation (GO:0006468), T cell activation (GO:0042110), negative regulation of apoptotic process (GO:0043066), positive regulation of DNA metabolic process (GO:0051054)

GO Molecular Function (11): 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), 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 (7): immunological synapse (GO:0001772), cytosol (GO:0005829), plasma membrane (GO:0005886), aggresome (GO:0016235), centriolar satellite (GO:0034451), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Immune System	2
Apoptotic execution phase	1
G alpha (q) signalling events	1
Platelet activation, signaling and aggregation	1
TCR signaling	1
The phototransduction cascade	1
Fc epsilon receptor (FCERI) signaling	1
Axon guidance	1
GPCR downstream signalling	1
Transcriptional regulation by RUNX1	1
RAF/MAP kinase cascade	1
Programmed Cell Death	1
Adaptive Immune System	1
RNA Polymerase II Transcription	1
Sensory Perception	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
positive regulation of cytokine production	3
intracellular anatomical structure	2
protein kinase activity	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
membrane protein proteolysis	1
defense response	1
axonogenesis	1
neuron projection guidance	1
telomere maintenance	1
regulation of telomere maintenance	1
positive regulation of DNA metabolic process	1
positive regulation of chromosome organization	1
interleukin-17 production	1
regulation of interleukin-17 production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
interleukin-4 production	1
regulation of interleukin-4 production	1
signal transduction	1
CD4-positive, alpha-beta T cell activation	1
alpha-beta T cell proliferation	1
Fc receptor signaling pathway	1
insulin receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
negative regulation of cellular response to insulin stimulus	1
T cell activation	1
regulation of T cell activation	1
positive regulation of lymphocyte activation	1
positive regulation of leukocyte cell-cell adhesion	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
negative regulation of lymphocyte apoptotic process	1

Protein interactions and networks

STRING

1914 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKCQ	CARD11	Q9BXL7	927
PRKCQ	CD28	P10747	919
PRKCQ	BCL10	O95999	902
PRKCQ	GLRX3	O76003	893
PRKCQ	MALT1	Q9UDY8	769
PRKCQ	PLCG1	P19174	725
PRKCQ	FYN	P06241	715
PRKCQ	LCK	P06239	710
PRKCQ	ZAP70	P43403	642
PRKCQ	GATA3	P23771	598
PRKCQ	IKBKG	Q9Y6K9	576
PRKCQ	TAGAP	Q8N103	571
PRKCQ	C1QTNF6	Q9BXI9	554
PRKCQ	REL	Q04864	549
PRKCQ	NFKB1	P19838	537

IntAct

53 interactions, top by confidence:

A	B	Type	Score
PRKCQ	FYN	psi-mi:“MI:0915”(physical association)	0.660
FYN	PRKCQ	psi-mi:“MI:0915”(physical association)	0.660
PRKCQ	FYN	psi-mi:“MI:0217”(phosphorylation reaction)	0.660
MAP4K3	PRKCQ	psi-mi:“MI:0915”(physical association)	0.640
MAP4K3	PRKCQ	psi-mi:“MI:0914”(association)	0.640
PRKCQ	MAP4K3	psi-mi:“MI:0407”(direct interaction)	0.640
MAP4K3	PRKCQ	psi-mi:“MI:0407”(direct interaction)	0.640
GLRX3	PRKCQ	psi-mi:“MI:0915”(physical association)	0.600
PRKCQ	GLRX3	psi-mi:“MI:0915”(physical association)	0.600
GLRX3	PRKCQ	psi-mi:“MI:0403”(colocalization)	0.600
PRKCQ	PRKCZ	psi-mi:“MI:0915”(physical association)	0.580
PRKCZ	PRKCQ	psi-mi:“MI:0915”(physical association)	0.580
PRKCQ	HSF1	psi-mi:“MI:0915”(physical association)	0.540
HSF1	PRKCQ	psi-mi:“MI:0217”(phosphorylation reaction)	0.540
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
PRKCQ	C2CD2L	psi-mi:“MI:0914”(association)	0.530
PRKCD	PRKCB	psi-mi:“MI:0914”(association)	0.530
BTK	PRKCQ	psi-mi:“MI:0915”(physical association)	0.520
MEF2A	Nfix	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (89): PRKCQ (Affinity Capture-MS), PRKCQ (Affinity Capture-MS), PRKCQ (Affinity Capture-Western), PRKCQ (Affinity Capture-Western), PRKCQ (Affinity Capture-MS), C2CD2L (Affinity Capture-MS), ZNF24 (Affinity Capture-MS), CARD11 (Biochemical Activity), PRKCQ (Biochemical Activity), PRKCQ (Affinity Capture-MS), PRKCQ (Affinity Capture-MS), PRKCQ (Phenotypic Enhancement), PRKCQ (Affinity Capture-Western), VAV1 (Affinity Capture-Western), FYN (Reconstituted Complex)

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: 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

36 interactions.

A	Effect	B	Mechanism
PRKCQ	up-regulates	RASGRP3	phosphorylation
PDPK1	up-regulates	PRKCQ	phosphorylation
MAP4K3	up-regulates	PRKCQ	phosphorylation
PRKCQ	up-regulates	RAPGEF2	phosphorylation
PRKCQ	up-regulates	HSF1	phosphorylation
1,2-diacyl-sn-glycerol	“up-regulates activity”	PRKCQ	binding
PRKCQ	“up-regulates activity”	ICAM3	phosphorylation
PRKCQ	unknown	MSN	phosphorylation
PRKCQ	“up-regulates activity”	CARD11	phosphorylation
PRKCQ	“down-regulates activity”	HABP4	phosphorylation
PRKCQ	“up-regulates activity”	PRKCQ	phosphorylation
PRKCQ	“down-regulates activity”	NOS3	phosphorylation
PRKCQ	“up-regulates activity”	FOSL1	phosphorylation
CARD10	“up-regulates activity”	PRKCQ	relocalization
PRKCQ	“up-regulates activity”	TBK1	phosphorylation
PRKCQ	“up-regulates activity”	PTPN7	phosphorylation
PRKCQ	“down-regulates activity”	PTPN6	phosphorylation
PRKCQ	“down-regulates activity”	KDM1A	phosphorylation
FYN	up-regulates	PRKCQ	phosphorylation
LCK	unknown	PRKCQ	phosphorylation
VAV1	up-regulates	PRKCQ
PRKCQ	“form complex”	PKCtheta/Nfix	binding
PRKCQ	“up-regulates quantity by expression”	ITGB1	“transcriptional regulation”
PRKCQ	“down-regulates activity”	IRS1	phosphorylation
PRKCQ	“up-regulates activity”	CBL	phosphorylation
PRKCQ	“up-regulates activity”	WIPF1	phosphorylation
PRKCQ	“up-regulates activity”	GRM5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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
TCR signaling	5	95.5×	4e-07
Signaling by the B Cell Receptor (BCR)	5	66.5×	1e-06
Fc epsilon receptor (FCERI) signaling	5	52.3×	3e-06
Platelet activation, signaling and aggregation	5	20.3×	1e-04
Signaling by Receptor Tyrosine Kinases	5	9.9×	2e-03
Innate Immune System	9	8.8×	2e-05
Adaptive Immune System	7	8.0×	4e-04
Hemostasis	5	6.9×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
T cell receptor signaling pathway	6	28.5×	2e-05
positive regulation of canonical NF-kappaB signal transduction	5	11.3×	4e-03
intracellular signal transduction	9	10.7×	2e-05
protein phosphorylation	5	10.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3691 predictions. Top by Δscore:

Variant	Effect	Δscore
10:6428364:T:C	acceptor_gain	1.0000
10:6428369:CAGAG:C	acceptor_gain	1.0000
10:6428373:G:GC	acceptor_gain	1.0000
10:6428374:T:C	acceptor_gain	1.0000
10:6428375:T:C	acceptor_gain	1.0000
10:6428375:T:TC	acceptor_gain	1.0000
10:6430804:CCTTA:C	donor_loss	1.0000
10:6430805:CTTA:C	donor_loss	1.0000
10:6430806:TTA:T	donor_loss	1.0000
10:6430807:TA:T	donor_loss	1.0000
10:6430808:A:AC	donor_gain	1.0000
10:6430809:C:CC	donor_gain	1.0000
10:6430809:C:CG	donor_loss	1.0000
10:6430809:CCA:C	donor_gain	1.0000
10:6441889:TTA:T	donor_loss	1.0000
10:6441890:TA:T	donor_loss	1.0000
10:6441891:ACC:A	donor_loss	1.0000
10:6442082:C:CC	acceptor_gain	1.0000
10:6442091:C:CT	acceptor_gain	1.0000
10:6456668:TCCTA:T	donor_loss	1.0000
10:6456669:CCTA:C	donor_loss	1.0000
10:6456670:CTACC:C	donor_loss	1.0000
10:6456671:TAC:T	donor_loss	1.0000
10:6456672:A:C	donor_loss	1.0000
10:6456673:C:T	donor_loss	1.0000
10:6456673:CCT:C	donor_gain	1.0000
10:6456808:GGTCC:G	acceptor_gain	1.0000
10:6456809:GTCC:G	acceptor_gain	1.0000
10:6456810:TCC:T	acceptor_gain	1.0000
10:6456811:CC:C	acceptor_gain	1.0000

AlphaMissense

4761 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:6428324:G:C	F668L	1.000
10:6428324:G:T	F668L	1.000
10:6428325:A:C	F668C	1.000
10:6428325:A:G	F668S	1.000
10:6428326:A:G	F668L	1.000
10:6428336:G:C	F664L	1.000
10:6428336:G:T	F664L	1.000
10:6428338:A:G	F664L	1.000
10:6430912:C:A	R621S	1.000
10:6430912:C:G	R621S	1.000
10:6430913:C:A	R621M	1.000
10:6430913:C:G	R621T	1.000
10:6441969:A:G	L587P	1.000
10:6441992:G:C	F579L	1.000
10:6441992:G:T	F579L	1.000
10:6441994:A:G	F579L	1.000
10:6441996:G:T	P578H	1.000
10:6442026:A:G	L568P	1.000
10:6442032:C:T	G566E	1.000
10:6442033:C:A	G566W	1.000
10:6442040:C:A	W563C	1.000
10:6442040:C:G	W563C	1.000
10:6442042:A:G	W563R	1.000
10:6442042:A:T	W563R	1.000
10:6442045:A:G	W562R	1.000
10:6442045:A:T	W562R	1.000
10:6442048:C:G	D561H	1.000
10:6456681:G:T	A547D	1.000
10:6456688:A:G	Y545H	1.000
10:6456699:C:T	G541E	1.000

dbSNP variants (sampled 300 via entrez): RS1000027317 (10:6471121 C>T), RS1000039652 (10:6551351 T>C), RS1000061540 (10:6471370 G>A), RS1000062107 (10:6509605 C>G,T), RS1000069675 (10:6467692 C>T), RS1000080618 (10:6467286 C>T), RS1000087480 (10:6506954 C>A), RS1000096997 (10:6423446 A>G), RS1000118407 (10:6513224 C>T), RS1000121346 (10:6523461 A>C), RS1000121381 (10:6434264 G>C), RS1000126846 (10:6465430 T>C), RS1000152318 (10:6434061 G>A), RS1000200304 (10:6570208 C>A), RS1000215466 (10:6394300 A>C,G)

Disease associations

OMIM: gene MIM:600448 | disease phenotypes: MIM:266600

GenCC curated gene-disease

Mondo (1): inflammatory bowel disease 1 (MONDO:0009960)

Orphanet (0):

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000232_7	Rheumatoid arthritis	4.000000e-06
GCST000258_2	Type 1 diabetes	4.000000e-09
GCST000392_1	Type 1 diabetes	1.000000e-07
GCST001491_11	Immune response to smallpox vaccine (IL-6)	3.000000e-08
GCST001911_1	Asthma (bronchodilator response)	2.000000e-07
GCST001945_3	Body mass index in asthmatics	7.000000e-06
GCST002318_76	Rheumatoid arthritis	3.000000e-10
GCST002318_92	Rheumatoid arthritis	4.000000e-10
GCST002520_4	Celiac disease	2.000000e-07
GCST004132_31	Crohn’s disease	2.000000e-08
GCST005523_27	Celiac disease	2.000000e-08
GCST005537_184	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	9.000000e-09
GCST006048_10	Rheumatoid arthritis (ACPA-positive)	1.000000e-08
GCST006959_175	Rheumatoid arthritis	3.000000e-08
GCST006959_20	Rheumatoid arthritis	3.000000e-09
GCST007401_17	Factor VII activity	2.000000e-06
GCST007798_94	Asthma	5.000000e-10
GCST007800_59	Asthma (childhood onset)	4.000000e-15
GCST007932_99	Medication use (thyroid preparations)	4.000000e-09
GCST007995_29	Asthma (childhood onset)	8.000000e-14
GCST008644_15	Celiac disease and Rheumatoid arthritis	8.000000e-11
GCST009798_72	Asthma	4.000000e-08
GCST009873_2	Autoimmune traits (pleiotropy)	1.000000e-08
GCST012125_2	Chronic pain	1.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004340	body mass index
EFO:0004619	factor VII measurement
EFO:0009933	Thyroid preparation use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2096620 (PROTEIN FAMILY), CHEMBL3920 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

37 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 473,684 (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
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3622821	UPADACITINIB	4	2,726
CHEMBL3813873	PEXIDARTINIB	4	3,586
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL265502	SURAMIN	3	36,848
CHEMBL38380	FASUDIL	3	11,953
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL140	CURCUMIN	3	93,882
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2
CHEMBL28509	EDELFOSINE	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL574737	UCN-01	2
CHEMBL1721885	SU-014813	2
CHEMBL1967878	CENISERTIB	2
CHEMBL1976040	ADAVOSERTIB	2
CHEMBL3982723	DAROVASERTIB	2
CHEMBL565612	SOTRASTAURIN	2
CHEMBL572878	TOZASERTIB	2

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4750316	PRKCQ		0.00	0
rs500766	PRKCQ		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Delta subfamily

Most potent curated ligand interactions (8 total), top 8:

Ligand	Action	Affinity	Parameter
PKCθ inhibitor 14	Inhibition	9.6	pIC50
darovasertib	Inhibition	9.4	pIC50
10-Me-Aplog-1	Activation	9.27	pKi
sotrastaurin	Inhibition	9.0	pIC50
GSK690693	Inhibition	8.7	pIC50
CC-90005	Inhibition	8.1	pIC50
compound 41 [PMID: 25000588]	Inhibition	7.64	pIC50
aplithianine A	Inhibition	7.44	pIC50

Binding affinities (BindingDB)

255 measured of 287 human assays (287 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
3-amino-N-[4-(4-aminopiperidin-1-yl)-3-pyridinyl]-6-(2-fluorophenyl)pyrazine-2-carboxamide	IC50	0.1 nM	US-9452998: Protein kinase C inhibitors and methods of their use
CHEMBL4578497	IC50	0.1 nM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[2-morpholin-4-yl-5-(trifluoromethyl)pyrimidin-4-yl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(3-morpholin-4-ylphenyl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[2-(3,6-dihydro-2H-pyran-4-yl)-5-(trifluoromethyl)pyrimidin-4-yl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-(2-morpholin-4-ylquinazolin-4-yl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[2-(trifluoromethyl)-1H-indol-4-yl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[6-(dimethylamino)-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[2-(4,4-difluoropiperidin-1-yl)-5-fluoropyrimidin-4-yl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(1-methylindol-4-yl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(1H-indazol-4-yl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(6-fluoro-2-morpholin-4-ylquinazolin-4-yl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(2-methyl-1H-indol-4-yl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(1H-indol-4-yl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[3-morpholin-4-yl-5-(trifluoromethyl)phenyl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-[4-amino-4-(hydroxymethyl)piperidin-1-yl]-2-pyridinyl]-6-[6-morpholin-4-yl-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
CHEMBL3741746	IC50	0.13 nM
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-(5-fluoro-2-morpholin-4-ylpyrimidin-4-yl)pyrazine-2-carboxamide	IC50	0.14 nM	US-9452998: Protein kinase C inhibitors and methods of their use
CHEMBL4528495	IC50	0.15 nM
3-amino-N-[3-[4-amino-4-(ethoxymethyl)piperidin-1-yl]-2-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.16 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[5-morpholin-4-yl-2-(trifluoromethyl)phenyl]pyrazine-2-carboxamide	IC50	0.17 nM	US-9452998: Protein kinase C inhibitors and methods of their use
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(6-morpholin-4-yl-2-pyridinyl)pyrazine-2-carboxamide	IC50	0.19 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[6-(azetidin-1-yl)-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.2 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[4-(4-aminopiperidin-1-yl)-3-pyridinyl]-6-phenylpyrazine-2-carboxamide	IC50	0.2 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[4-(4-aminopiperidin-1-yl)-3-pyridinyl]-6-(4-methoxyphenyl)pyrazine-2-carboxamide	IC50	0.2 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-6-(2-fluorophenyl)-N-(4-piperazin-1-yl-3-pyridinyl)pyrazine-2-carboxamide	IC50	0.2 nM	US-9452998: Protein kinase C inhibitors and methods of their use
CHEMBL4435580	IC50	0.22 nM
3-amino-N-[3-[(1S,5R,8S)-8-amino-6-oxa-3-azabicyclo[3.2.1]octan-3-yl]-2-pyridinyl]-6-[6-morpholin-4-yl-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.24 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-[(3S,4R)-4-amino-3-fluoropiperidin-1-yl]-2-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.25 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-[4-amino-4-(hydroxymethyl)piperidin-1-yl]-2-pyridinyl]-6-(1-morpholin-4-ylisoquinolin-3-yl)pyrazine-2-carboxamide	IC50	0.25 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[6-[[(2R)-1-hydroxypropan-2-yl]amino]-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.26 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(1-methylpyrazolo[3,4-d]pyrimidin-4-yl)pyrazine-2-carboxamide	IC50	0.27 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(2-morpholin-4-ylpyrimidin-4-yl)pyrazine-2-carboxamide	IC50	0.29 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[2-morpholin-4-yl-5-(trifluoromethyl)pyrimidin-4-yl]pyrazine-2-carboxamide	IC50	0.3 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-3-fluoropiperidin-1-yl)-2-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.3 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[6-[(3S)-3-methylmorpholin-4-yl]-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.32 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazine-2-carboxamide	IC50	0.33 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(3-fluoro-2-pyridinyl)pyrazine-2-carboxamide	IC50	0.33 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-6-(2-amino-5-chloropyrimidin-4-yl)-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.35 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-3-methoxypiperidin-1-yl)-2-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.36 nM	US-9452998: Protein kinase C inhibitors and methods of their use
CHEMBL4587471	IC50	0.36 nM
CHEMBL4540382	IC50	0.38 nM
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[6-cyclopropyl-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.4 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-(3-cyano-2-pyridinyl)pyrazine-2-carboxamide	IC50	0.4 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-(2-carbamoyl-5-fluoropyrimidin-4-yl)pyrazine-2-carboxamide	IC50	0.4 nM	US-9452998: Protein kinase C inhibitors and methods of their use
CHEMBL4580751	IC50	0.42 nM
CHEMBL4575526	IC50	0.44 nM

ChEMBL bioactivities

1445 potent at pChembl≥5 of 1574 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	Ki	0.08	nM	CHEMBL2326002
10.10	IC50	0.08	nM	STAUROSPORINE
10.07	IC50	0.086	nM	CHEMBL4082370
10.05	IC50	0.09	nM	CHEMBL4442196
10.00	IC50	0.1	nM	CHEMBL2151411
10.00	Ki	0.1	nM	CHEMBL2326001
10.00	Ki	0.1	nM	CHEMBL2326000
10.00	Ki	0.1	nM	CHEMBL2325998
10.00	IC50	0.1	nM	CHEMBL4578497
10.00	IC50	0.1	nM	CHEMBL5631319
10.00	IC50	0.1	nM	CHEMBL5632236
9.96	Ki	0.11	nM	DEBROMOAPLYSIATOXIN
9.89	IC50	0.13	nM	CHEMBL3921551
9.89	IC50	0.13	nM	CHEMBL3920517
9.89	IC50	0.13	nM	CHEMBL3741746
9.85	IC50	0.14	nM	CHEMBL3586039
9.85	IC50	0.14	nM	CHEMBL4575056
9.82	IC50	0.15	nM	CHEMBL4528495
9.80	IC50	0.16	nM	CHEMBL3893533
9.80	Ki	0.16	nM	APLYSIATOXIN
9.77	IC50	0.17	nM	CHEMBL4538431
9.74	IC50	0.18	nM	CHEMBL4065996
9.74	IC50	0.18	nM	CHEMBL4443190
9.72	EC50	0.19	nM	CHEMBL3741746
9.70	Ki	0.2	nM	CHEMBL2326007
9.70	Ki	0.2	nM	DEMETHOXYDEBROMOAPLYSIATOXIN
9.70	IC50	0.2	nM	CHEMBL3966595
9.70	Ki	0.2	nM	CHEMBL4469412
9.70	IC50	0.2	nM	CHEMBL3982497
9.66	IC50	0.22	nM	CHEMBL4435580
9.66	IC50	0.22	nM	SOTRASTAURIN
9.64	IC50	0.23	nM	CHEMBL3982497
9.64	IC50	0.23	nM	CHEMBL4547465
9.62	IC50	0.24	nM	CHEMBL3907088
9.60	IC50	0.25	nM	CHEMBL3798011
9.60	IC50	0.25	nM	CHEMBL3943813
9.57	IC50	0.27	nM	CHEMBL3984070
9.57	IC50	0.27	nM	CHEMBL3937993
9.55	IC50	0.28	nM	CHEMBL571581
9.54	IC50	0.29	nM	CHEMBL3987185
9.52	IC50	0.3	nM	CHEMBL3892099
9.52	Ki	0.3	nM	CHEMBL4528271
9.52	IC50	0.3	nM	CHEMBL3966643
9.52	IC50	0.3	nM	SOTRASTAURIN
9.50	Ki	0.3162	nM	CHEMBL1996510
9.49	IC50	0.32	nM	CHEMBL3586038
9.49	IC50	0.32	nM	CHEMBL1082225
9.48	IC50	0.33	nM	CHEMBL3967601
9.48	IC50	0.33	nM	CHEMBL3895998
9.44	IC50	0.36	nM	CHEMBL3969856

PubChem BioAssay actives

1216 with measured affinity, of 3229 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
4-N-[[(3S)-1-ethylpiperidin-3-yl]methyl]-5-fluoro-2-N-[3-methoxy-5-(5-methyltetrazol-1-yl)phenyl]pyrimidine-2,4-diamine	1231896: Inhibition of human full length PKCtheta assessed as fluorescence intensity after 60 mins	ic50	0.0001	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-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
5-fluoro-2-[(3S)-3-[(2R)-2-hydroxy-3-methylbutan-2-yl]piperazin-1-yl]-6-(2H-pyrazolo[3,4-b]pyridin-3-yl)pyridin-3-ol	728627: Inhibition of full-length recombinant PKC theta (unknown origin) using ERMRPRKRQGSVRRRV as substrate after 60 mins by scintillation counting analysis in presence of [gamma-33P]ATP	ki	0.0001	uM
1-[3-chloro-6-(1,4-diazepan-1-yl)-2-pyridinyl]-7-ethoxy-3H-imidazo[4,5-b]pyridin-2-one	1450036: Inhibition of N-terminal FLAG-tagged PKCtheta (unknown origin) expressed in baculovirus expression system using fluorescein-PKC as substrate preincubated for 5 mins followed by substrate addition measured after 60 mins in presence of ATP by Lathascreen TR-FRET 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
16,16-dimethyl-10-oxa-2,4,6,15,17,22-hexazapentacyclo[13.6.2.12,5.019,23.09,24]tetracosa-1(22),5,7,9(24),19(23),20-hexaene-3,18-dione	2139570: Inhibition of PKC theta (unknown origin) in presence of ATP at Km	ic50	0.0001	uM
11,15,15-trimethyl-10-oxa-2,4,6,14,16,21-hexazapentacyclo[12.6.2.12,5.018,22.09,23]tricosa-1(21),5,7,9(23),18(22),19-hexaene-3,17-dione	2139570: Inhibition of PKC theta (unknown origin) in presence of ATP at Km	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
(2R)-2-[(2S)-4-[3,5-difluoro-6-(2H-pyrazolo[3,4-b]pyridin-3-yl)-2-pyridinyl]piperazin-2-yl]-3-methylbutan-2-ol	728627: Inhibition of full-length recombinant PKC theta (unknown origin) using ERMRPRKRQGSVRRRV as substrate after 60 mins by scintillation counting analysis in presence of [gamma-33P]ATP	ki	0.0001	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	728627: Inhibition of full-length recombinant PKC theta (unknown origin) using ERMRPRKRQGSVRRRV as substrate after 60 mins by scintillation counting analysis in presence of [gamma-33P]ATP	ki	0.0001	uM
(2R)-2-[(2S)-4-[5-fluoro-3-(hydroxymethyl)-6-(2H-pyrazolo[3,4-b]pyridin-3-yl)-2-pyridinyl]piperazin-2-yl]-3-methylbutan-2-ol	728627: Inhibition of full-length recombinant PKC theta (unknown origin) using ERMRPRKRQGSVRRRV as substrate after 60 mins by scintillation counting analysis in presence of [gamma-33P]ATP	ki	0.0001	uM
3-(7-methyl-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	690003: Inhibition of PKCtheta by scintillation proximity assay	ic50	0.0001	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	687835: Inhibition of [3H]PDBu binding to PKCtheta C1B domain	ki	0.0001	uM
4-[[4-[(4-aminocyclohexyl)amino]-1-adamantyl]methylamino]-2-[[2-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carbonitrile	1572469: Inhibition of recombinant human full length PKCtheta using biotin-labelled STK substrate-1 as substrate after 60 mins by fluorescence assay	ic50	0.0001	uM
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	1902444: Inhibition of full length human PKCtheta using 5-FAM-RFARKGSLRQKNV-OH peptide substrate incubated for 30 mins by IMAP kinase assay	ic50	0.0002	uM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(3-morpholin-4-ylisoquinolin-1-yl)pyrazine-2-carboxamide	2098473: Inhibition of PKCtheta (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0002	uM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(1H-indol-4-yl)pyrazine-2-carboxamide	2098473: Inhibition of PKCtheta (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0002	uM
tert-butyl 4-[5-nitro-6-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)-2-pyridinyl]-3-phenylpiperazine-1-carboxylate	1450036: Inhibition of N-terminal FLAG-tagged PKCtheta (unknown origin) expressed in baculovirus expression system using fluorescein-PKC as substrate preincubated for 5 mins followed by substrate addition measured after 60 mins in presence of ATP by Lathascreen TR-FRET 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-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,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	517269: Inhibition of [3H]PDBu binding to PKCtheta C1B peptide	ki	0.0002	uM
2-methyl-2-[3-(1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl]pent-4-yn-1-amine	1600582: Inhibition of human recombinant full length His tagged PKC theta expressed in baculovirus using ERMRPRKRQGSVRRRV peptide as substrate incubated for 60 mins in presence of [33P] gammaATP by microbeta liquid scintillation counter	ki	0.0002	uM
(2R)-2-[(2S)-4-[5-fluoro-6-(2H-pyrazolo[3,4-b]pyridin-3-yl)-2-pyridinyl]piperazin-2-yl]-3-methylbutan-2-ol	728627: Inhibition of full-length recombinant PKC theta (unknown origin) using ERMRPRKRQGSVRRRV as substrate after 60 mins by scintillation counting analysis in presence of [gamma-33P]ATP	ki	0.0002	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	768060: Displacement of [3H]PDBu from PKCtheta C1B domain (unknown origin)	ki	0.0002	uM
4-[[4-[(4-hydroxycyclohexyl)methylamino]-1-adamantyl]methylamino]-2-[(2-propan-2-ylsulfanyl-3-pyridinyl)methylamino]pyrimidine-5-carbonitrile	1572469: Inhibition of recombinant human full length PKCtheta using biotin-labelled STK substrate-1 as substrate after 60 mins by fluorescence assay	ic50	0.0002	uM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[6-morpholin-4-yl-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	2098473: Inhibition of PKCtheta (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0003	uM
5-fluoro-2-N-[3-methoxy-5-(5-methyltetrazol-1-yl)phenyl]-4-N-[[(3S)-1-methylpiperidin-3-yl]methyl]pyrimidine-2,4-diamine	1231896: Inhibition of human full length PKCtheta assessed as fluorescence intensity after 60 mins	ic50	0.0003	uM
4-[(4-methyl-1H-indol-5-yl)amino]-5-[5-[(4-methylpiperazin-1-yl)methyl]-1-benzofuran-2-yl]pyridine-3-carbonitrile	447950: Inhibition of human PKCtheta by IMAP fluorescence polarization technology	ic50	0.0003	uM
2-[3-(3-chloro-2H-pyrazolo[3,4-b]pyridin-4-yl)phenyl]-2-methylbutan-1-amine	1600582: Inhibition of human recombinant full length His tagged PKC theta expressed in baculovirus using ERMRPRKRQGSVRRRV peptide as substrate incubated for 60 mins in presence of [33P] gammaATP by microbeta liquid scintillation counter	ki	0.0003	uM
4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-[6-(piperazin-1-ylmethyl)-2-pyridinyl]ethenyl]pyridine-3-carbonitrile	463329: Inhibition of PKCtheta	ic50	0.0003	uM
2,2-dimethyl-7-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)-1-[(1R)-1-phenylethyl]-3H-quinazolin-4-one	1298481: Inhibition of N-terminal FLAG-tagged PKCtheta (unknown origin) expressed in baculovirus preincubated for 5 mins using fluorescein-PKC substrate measured after 60 mins in presence of ATP by TR-FRET assay	ic50	0.0003	uM
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	1768630: Inhibition of PKA-theta (unknown origin) using Fam-labelled S6-derived peptide incubated for 2 hrs by TR-FRET assay	ic50	0.0004	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
6-methyl-4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-[3-(4-methylpiperazin-1-yl)sulfonylphenyl]ethenyl]pyridine-3-carbonitrile	469102: Inhibition of PKCtheta	ic50	0.0004	uM
2-methyl-2-[3-[3-(trifluoromethyl)-2H-pyrazolo[3,4-b]pyridin-4-yl]phenyl]butan-1-amine	1600582: Inhibition of human recombinant full length His tagged PKC theta expressed in baculovirus using ERMRPRKRQGSVRRRV peptide as substrate incubated for 60 mins in presence of [33P] gammaATP by microbeta liquid scintillation counter	ki	0.0004	uM
4-[[4-[(4-hydroxycyclohexyl)amino]-1-adamantyl]methylamino]-2-[[2-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carbonitrile	1572469: Inhibition of recombinant human full length PKCtheta using biotin-labelled STK substrate-1 as substrate after 60 mins by fluorescence assay	ic50	0.0004	uM
4-[[4-[(4-hydroxycyclohexyl)methylamino]-1-adamantyl]methylamino]-2-[[2-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carbonitrile	1572469: Inhibition of recombinant human full length PKCtheta using biotin-labelled STK substrate-1 as substrate after 60 mins by fluorescence assay	ic50	0.0004	uM
4-[[4-[(4-hydroxycyclohexyl)methylamino]-1-adamantyl]methylamino]-2-[(2-methylsulfanyl-3-pyridinyl)methylamino]pyrimidine-5-carbonitrile	1572469: Inhibition of recombinant human full length PKCtheta using biotin-labelled STK substrate-1 as substrate after 60 mins by fluorescence assay	ic50	0.0004	uM
1-benzyl-2,2-dimethyl-7-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)-3H-quinazolin-4-one	1298481: Inhibition of N-terminal FLAG-tagged PKCtheta (unknown origin) expressed in baculovirus preincubated for 5 mins using fluorescein-PKC substrate measured after 60 mins in presence of ATP by TR-FRET assay	ic50	0.0005	uM
3-(1H-indol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	690003: Inhibition of PKCtheta by scintillation proximity assay	ic50	0.0005	uM
5-fluoro-4-N-[[(3S)-1-(2-methoxyethyl)piperidin-3-yl]methyl]-2-N-[3-methoxy-5-(5-methyltetrazol-1-yl)phenyl]pyrimidine-2,4-diamine	1231896: Inhibition of human full length PKCtheta assessed as fluorescence intensity after 60 mins	ic50	0.0005	uM
14-methyl-10-oxa-2,4,6,18,22-pentazapentacyclo[13.6.2.12,5.019,23.09,24]tetracosa-1(22),5,7,9(24),15(23),16,18,20-octaen-3-one	2139570: Inhibition of PKC theta (unknown origin) in presence of ATP at Km	ic50	0.0005	uM
21-fluoro-11,14-dimethyl-10-oxa-2,4,6,15,22-pentazapentacyclo[13.6.2.12,5.019,23.09,24]tetracosa-1(21),5,7,9(24),16,19,22-heptaene-3,18-dione	2139570: Inhibition of PKC theta (unknown origin) in presence of ATP at Km	ic50	0.0005	uM
19-oxo-7,12-dioxa-1,16,18,21-tetrazatetracyclo[11.6.1.12,6.017,20]henicosa-2(21),3,5,13(20),14,16-hexaene-5-carboxamide	2139570: Inhibition of PKC theta (unknown origin) in presence of ATP at Km	ic50	0.0005	uM
11,14-dimethyl-10-oxa-2,4,6,14,18,22-hexazapentacyclo[13.6.2.12,5.019,23.09,24]tetracosa-1(22),5,7,9(24),15(23),16,18,20-octaen-3-one	2139570: Inhibition of PKC theta (unknown origin) in presence of ATP at Km	ic50	0.0005	uM
11,14-dimethyl-10-oxa-2,4,6,18,22-pentazapentacyclo[13.6.2.12,5.019,23.09,24]tetracosa-1(22),5,7,9(24),15(23),16,18,20-octaen-3-one	2139570: Inhibition of PKC theta (unknown origin) in presence of ATP at Km	ic50	0.0005	uM
21-fluoro-11,14-dimethyl-10-oxa-2,4,6,14,18,22-hexazapentacyclo[13.6.2.12,5.019,23.09,24]tetracosa-1(22),5,7,9(24),15(23),16,18,20-octaen-3-one	2139570: Inhibition of PKC theta (unknown origin) in presence of ATP at Km	ic50	0.0005	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases abundance	3
Arsenic	affects methylation, decreases expression, decreases phosphorylation, increases abundance	3
Valproic Acid	affects expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	2
Nickel	increases expression	2
Quercetin	decreases reaction, increases expression	2
Tetrachlorodibenzodioxin	decreases response to substance, affects localization, affects binding, increases reaction, increases activity	2
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, affects methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation	1
puag-haad	increases expression	1
rottlerin	decreases activity	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
pomalidomide	affects cotreatment, increases activity, increases reaction	1
abrine	decreases expression	1
incobotulinumtoxinA	decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Ascorbic Acid	affects cotreatment, increases expression	1
Cannabinoids	affects methylation, increases abundance	1
Chelating Agents	affects binding, decreases expression	1
Cisplatin	increases expression	1
Coal	decreases expression, decreases phosphorylation, increases abundance	1
Copper	affects binding, decreases expression	1
Dietary Carbohydrates	affects cotreatment, decreases expression	1

ChEMBL screening assays

754 unique, capped per target: 743 binding, 11 functional

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

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7YK	Ubigene A-549 PRKCQ KO	Cancer cell line	Male
CVCL_D9PP	Ubigene HEK293 PRKCQ KO	Transformed cell line	Female
CVCL_TG92	HAP1 PRKCQ (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01585155	PHASE3	COMPLETED	Clinical Study of TA-650 in Pediatric Patients With Ulcerative Colitis
NCT04348890	PHASE1/PHASE2	WITHDRAWN	Proof of Concept Trial of Vamorolone in Pediatric Ulcerative Colitis
NCT02694042	Not specified	TERMINATED	Mission is Remission®: How Can a Disease Self-management Website Change Care?
NCT02985489	Not specified	WITHDRAWN	Pre-Operative Parenteral Nutrition in Malnourished Patients
NCT03827109	Not specified	TERMINATED	Peer Mentoring to Improve Self-management in Youth With IBD
NCT04207008	Not specified	COMPLETED	Trial of a Decision Support Intervention for Adolescents and Young Adults With Ulcerative Colitis
NCT04867408	Not specified	RECRUITING	Endoscopic Severity Image Recognition to Advance Research and Training in Inflammatory Bowel Disease (EVEREST - IBD)
NCT05591976	Not specified	COMPLETED	Exercise Training in Youth With Inflammatory Bowel Disease
NCT05673278	Not specified	UNKNOWN	Non-Invasive Monitoring Through Bowel Ultrasound in Paediatric Inflammatory Bowel Disease Study
NCT07198113	Not specified	RECRUITING	COMPARE - Pediatric Inflammatory Bowel Disease (PIBD)