PRKD3

Summary

PRKD3 (protein kinase D3, HGNC:9408) is a protein-coding gene on chromosome 2p22.2, encoding Serine/threonine-protein kinase D3 (O94806). Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC.

This gene belongs to the multigene protein kinase D family of serine/threonine kinases, which bind diacylglycerol and phorbol esters. Members of this family are characterized by an N-terminal regulatory domain comprised of a tandem repeat of cysteine-rich zinc-finger motifs and a pleckstrin domain. The C-terminal region contains the catalytic domain and is distantly related to calcium-regulated kinases. Catalytic activity of this enzyme promotes its nuclear localization. This protein has been implicated in a variety of functions including negative regulation of human airway epithelial barrier formation, growth regulation of breast and prostate cancer cells, and vesicle trafficking.

Source: NCBI Gene 23683 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 84 total
• GTEx eGene: eQTL in 45 tissues, sQTL in 25 (q < 0.05)
• ChEMBL bioactivity: 62 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.68 (unconstrained)
• MANE Select transcript: NM_005813
• Notable: 84 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9408
Approved symbol	PRKD3
Name	protein kinase D3
Location	2p22.2
Locus type	gene with protein product
Status	Approved
Aliases	PKD3, EPK2
Ensembl gene	ENSG00000115825
Ensembl biotype	protein_coding
OMIM	607077
Entrez	23683

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 17 protein_coding, 8 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000234179

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 2, TSL 4: 3, TSL 5: 1

ENST00000234179, ENST00000379066, ENST00000443187, ENST00000443977, ENST00000452104, ENST00000464552, ENST00000469275, ENST00000475912, ENST00000477132, ENST00000494667, ENST00000887822, ENST00000933385, ENST00000933386, ENST00000933387, ENST00000933388, ENST00000933389, ENST00000933390, ENST00001002271, ENST00001002272, ENST00001011567, ENST00001011568, ENST00001086046, ENST00001086047, ENST00001086048, ENST00001086049, ENST00001086050, ENST00001086051, ENST00001110303, ENST00001110304, ENST00001143406

RefSeq mRNA: 1 — MANE Select: NM_005813 NM_005813

CCDS: CCDS1789

Canonical transcript exons

ENST00000234179 — 19 exons

Exon	Start	End
ENSE00001479694	37316237	37317179
ENSE00003535964	37272380	37272432
ENSE00003544987	37293133	37293271
ENSE00003553892	37290868	37290999
ENSE00003568681	37277866	37277989
ENSE00003573308	37267430	37267536
ENSE00003583881	37260223	37260384
ENSE00003598470	37269615	37269687
ENSE00003624331	37289356	37289513
ENSE00003638671	37286177	37286369
ENSE00003641683	37282542	37282619
ENSE00003649347	37275767	37275844
ENSE00003650125	37274421	37274697
ENSE00003654574	37256662	37256929
ENSE00003670761	37279746	37279929
ENSE00003676063	37259583	37259681
ENSE00003892067	37250502	37253350
ENSE00003896164	37254204	37254289
ENSE00003901272	37324681	37324833

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 96.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.2560 / max 197.0390, expressed in 1731 samples.

Highest expression (Bgee): calcaneal tendon, buccal mucosa cell, sperm, tendon, corpus epididymis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRKD3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 45 tissues and its splicing (sQTL) in 25 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 70 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	sqtl	1.3e-81	+1.00	2:37292936:G:T
Thyroid	eqtl	8.9e-49	-0.42	2:37292936:G:T
Cells Cultured fibroblasts	sqtl	2.6e-43	+0.82	2:37292936:G:T
Nerve Tibial	eqtl	2.6e-37	-0.28	2:37238166:A:G
Spleen	eqtl	4.5e-32	-0.60	2:37292826:A:G
Lung	eqtl	6.2e-28	-0.26	2:37292936:G:T
Esophagus Muscularis	eqtl	1.0e-25	-0.34	2:37239703:G:A
Whole Blood	eqtl	3.0e-25	-0.23	2:37280201:T:C
Artery Aorta	eqtl	1.2e-23	-0.37	2:37292936:G:T
Heart Atrial Appendage	eqtl	2.5e-23	-0.26	2:37238166:A:G
Artery Tibial	eqtl	8.5e-19	-0.26	2:37238166:A:G
Testis	sqtl	1.7e-18	+0.79	2:37292936:G:T
Heart Left Ventricle	eqtl	1.2e-17	-0.27	2:37288737:T:G
Esophagus Gastroesophageal Junction	eqtl	2.4e-17	-0.34	2:37239703:G:A
Esophagus Mucosa	eqtl	2.4e-16	-0.27	2:37262480:C:A
Colon Sigmoid	eqtl	5.3e-16	-0.24	2:37260580:G:A
Skin Sun Exposed Lower leg	eqtl	6.0e-16	-0.22	2:37239703:G:A
Adipose Subcutaneous	sqtl	6.9e-16	-1.04	2:37305541:T:C
Artery Coronary	eqtl	1.7e-15	-0.45	2:37299694:A:C
Skin Not Sun Exposed Suprapubic	eqtl	1.9e-13	-0.25	2:37239703:G:A

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
27783	13.3356	1717
27784	0.7577	521
27779	0.4622	234
27782	0.3611	163
27778	0.0893	24
27777	0.0753	21
27781	0.0689	16
27776	0.0579	9
27780	0.0481	11

Top tissues by expression

showing 100 of 296 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.35	gold quality
buccal mucosa cell	CL:0002336	94.95	gold quality
sperm	CL:0000019	94.23	gold quality
tendon	UBERON:0000043	93.05	gold quality
corpus epididymis	UBERON:0004359	92.23	gold quality
cauda epididymis	UBERON:0004360	92.18	gold quality
skin of hip	UBERON:0001554	92.12	gold quality
parietal pleura	UBERON:0002400	91.64	gold quality
male germ cell	CL:0000015	91.38	gold quality
tibia	UBERON:0000979	90.98	gold quality
cartilage tissue	UBERON:0002418	90.96	gold quality
superficial temporal artery	UBERON:0001614	90.84	gold quality
pleura	UBERON:0000977	90.45	gold quality
colonic epithelium	UBERON:0000397	90.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.14	gold quality
ventricular zone	UBERON:0003053	90.00	gold quality
caput epididymis	UBERON:0004358	89.95	gold quality
stromal cell of endometrium	CL:0002255	89.94	gold quality
endometrium	UBERON:0001295	89.62	gold quality
blood vessel layer	UBERON:0004797	89.53	gold quality
visceral pleura	UBERON:0002401	89.28	gold quality
adrenal tissue	UBERON:0018303	89.18	gold quality
right adrenal gland cortex	UBERON:0035827	89.13	gold quality
ganglionic eminence	UBERON:0004023	88.90	gold quality
vermiform appendix	UBERON:0001154	88.86	gold quality
lymph node	UBERON:0000029	88.82	gold quality
tonsil	UBERON:0002372	88.66	gold quality
tendon of biceps brachii	UBERON:0008188	88.51	gold quality
adrenal cortex	UBERON:0001235	88.36	gold quality
adrenal gland	UBERON:0002369	88.33	gold quality
upper leg skin	UBERON:0004262	88.15	gold quality
left adrenal gland cortex	UBERON:0035825	88.14	gold quality
left adrenal gland	UBERON:0001234	88.04	gold quality
right adrenal gland	UBERON:0001233	88.02	gold quality
caecum	UBERON:0001153	87.99	gold quality
monocyte	CL:0000576	87.91	gold quality
mononuclear cell	CL:0000842	87.89	gold quality
leukocyte	CL:0000738	87.76	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.56	gold quality
lower lobe of lung	UBERON:0008949	87.37	gold quality
bone marrow cell	CL:0002092	87.36	gold quality
mammary duct	UBERON:0001765	87.17	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.56	gold quality
thoracic mammary gland	UBERON:0005200	86.55	gold quality
mammary gland	UBERON:0001911	86.48	gold quality
uterus	UBERON:0000995	86.47	gold quality
gastrocnemius	UBERON:0001388	86.45	gold quality
smooth muscle tissue	UBERON:0001135	86.28	gold quality
embryo	UBERON:0000922	86.27	gold quality
epithelium of mammary gland	UBERON:0003244	86.21	gold quality
periodontal ligament	UBERON:0008266	86.16	silver quality
connective tissue	UBERON:0002384	86.12	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.03	gold quality
gall bladder	UBERON:0002110	86.01	gold quality
seminal vesicle	UBERON:0000998	85.99	gold quality
pigmented layer of retina	UBERON:0001782	85.99	gold quality
sigmoid colon	UBERON:0001159	85.98	gold quality
adipose tissue	UBERON:0001013	85.93	gold quality
muscle of leg	UBERON:0001383	85.90	gold quality
synovial joint	UBERON:0002217	85.90	gold quality
right lung	UBERON:0002167	85.87	gold quality
tibial nerve	UBERON:0001323	85.86	gold quality
descending thoracic aorta	UBERON:0002345	85.79	gold quality
right coronary artery	UBERON:0001625	85.66	gold quality
spleen	UBERON:0002106	85.66	gold quality
urinary bladder	UBERON:0001255	85.52	gold quality
germinal epithelium of ovary	UBERON:0001304	85.51	gold quality
tibial artery	UBERON:0007610	85.49	gold quality
popliteal artery	UBERON:0002250	85.48	gold quality
mucosa of stomach	UBERON:0001199	85.45	gold quality
islet of Langerhans	UBERON:0000006	85.44	gold quality
endocervix	UBERON:0000458	85.36	gold quality
ovary	UBERON:0000992	85.29	gold quality
body of uterus	UBERON:0009853	85.26	gold quality
aorta	UBERON:0000947	85.17	gold quality
myometrium	UBERON:0001296	85.13	gold quality
urethra	UBERON:0000057	85.10	gold quality
trabecular bone tissue	UBERON:0002483	85.07	gold quality
female reproductive system	UBERON:0000474	85.06	gold quality
bone element	UBERON:0001474	84.98	gold quality
lung	UBERON:0002048	84.94	gold quality
mammalian vulva	UBERON:0000997	84.89	gold quality
thoracic aorta	UBERON:0001515	84.76	gold quality
rectum	UBERON:0001052	84.67	gold quality
ascending aorta	UBERON:0001496	84.67	gold quality
left coronary artery	UBERON:0001626	84.65	gold quality
bone marrow	UBERON:0002371	84.43	gold quality
coronary artery	UBERON:0001621	84.20	gold quality
left ovary	UBERON:0002119	84.20	gold quality
eye	UBERON:0000970	84.12	gold quality
right ovary	UBERON:0002118	84.07	gold quality
penis	UBERON:0000989	84.03	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.03	gold quality
sural nerve	UBERON:0015488	84.02	gold quality
testis	UBERON:0000473	83.88	gold quality
medial globus pallidus	UBERON:0002477	83.87	gold quality
oral cavity	UBERON:0000167	83.86	gold quality
omental fat pad	UBERON:0010414	83.86	gold quality
peritoneum	UBERON:0002358	83.85	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.24
E-GEOD-100618	no	467.01

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Retina	tissue	38.5
Lymph node	tissue	27.1	medium
Tonsil	tissue	27.1	medium
Spinal cord	tissue	24.3
Superior colliculi	tissue	22.2
Spleen	tissue	22.0	medium
Periaqueductal gray	tissue	21.9
Testis	tissue	21.8	high
Midbrain	tissue	21.8
Substantia nigra	tissue	21.8
Thalamus	tissue	21.2
Medulla oblongata	tissue	21.1
Pons	tissue	20.0
Thymus	tissue	19.3
Hypothalamus	tissue	19.1
Cervix	tissue	18.2	not detected
Ovary	tissue	18.2	medium
Endometrium 1	tissue	17.7	low
Corpus callosum	tissue	17.4
Appendix	tissue	17.1	medium
Adrenal gland	tissue	15.9	high
Septum	tissue	15.3
Smooth muscle	tissue	15.1	high
Hippocampal formation	tissue	14.8
Putamen	tissue	14.7
Amygdala	tissue	14.7
Urinary bladder	tissue	14.5	low
Adipose tissue	tissue	14.1	high
Placenta	tissue	14.0	high
Lung	tissue	13.9	high
Ventral forebrain	tissue	13.9
Breast	tissue	13.4	high
Epididymis	tissue	13.0	medium
Caudate putamen	tissue	12.9
Thyroid gland	tissue	12.6	medium
Gallbladder	tissue	12.5	high
Basal ganglia	tissue	12.3	medium
Entorhinal cortex	tissue	12.2
Cerebral cortex	tissue	11.9	medium
Temporal cortex	tissue	11.9
Seminal vesicle	tissue	11.8	medium
Stomach 1	tissue	11.7	medium
Nucleus accumbens	tissue	11.7
Hippocampus	tissue	11.7	medium
Motor cortex	tissue	11.6
Skin 1	tissue	11.5	not detected
Olfactory bulb	tissue	11.5
Locus coeruleus	tissue	11.4
Insular cortex	tissue	11.4
Tongue	tissue	11.3
Kidney	tissue	11.2	high
Prefrontal cortex	tissue	11.0
Parathyroid gland	tissue	11.0	medium
Colon	tissue	11.0	medium
Prostate	tissue	11.0	medium
Retrosplenial and cingulate cortex	tissue	10.9
Retrosplenial cortex	tissue	10.9
Postcentral gyrus	tissue	10.7
Rectum	tissue	10.3	medium
Esophagus	tissue	10.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Ventral spinal cord (24.3), Dorsal spinal cord (23.8), Posterior thalamic nucleus (17.5), White matter (17.4), Cerebellar cortex (16.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, GATA4, NFKB, NKX2-5, RELA

miRNA regulators (miRDB)

Targeting PRKD3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 174 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4725-3P	99.96	69.53	2520

Functional genomics

gnomAD constraint: pLI 8.72e-06, LOEUF 0.682, missense Z 0.938 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000234179 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:37,253,180–37,256,692	125 / 120.6	1.04	no
2:37,256,693–37,269,685	184 / 275.1	0.67	no
2:37,269,686–37,316,524	710 / 692.7	1.02	no

Literature-anchored findings (GeneRIF, showing 35)

• Novel isoforms regulate human keratinocyte differentiation by activating a p38 delta mitogen-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha. (PMID:12080077)
• PKCnu is an important component of signaling pathways downstream from novel PKC enzymes after B-cell receptor engagement (PMID:12506120)
• the effect of G protein-coupled receptor agonists on the regulatory properties, continuous shuttling, and intracellular distribution of Protein kinase C nu/protein kinase D3 (PMID:12676944)
• specificity of different PKD isoforms in regulating protein trafficking from the trans-Golgi network (PMID:14743217)
• PKD3 directly contributes to insulin-independent basal glucose uptake in L6 skeletal muscle cells. (PMID:15496505)
• Expression of constitutively activated PKCeta caused Golgi fragmentation. (PMID:15824133)
• the catalytic activity of PKD3 may regulate its nuclear import through autophosphorylation and/or interaction with another protein (PMID:16380377)
• The vesicular distribution may be attributed in part to the direct interaction between PKD3 and vesicle-associated membrane protein VAMP2, through which PKD3 may regulate VAMP2 vesicle trafficking by facilitating its recruitment to the target membrane. (PMID:17196367)
• A pathway comprising PKCs>Raf-1>MEK-1>ERK-1/-2 mediates the effect of gastrin on the CgA promoter, and strongly suggests that enhanced phosphorylation of Sp1 and CREB is crucial for CgA transactivation through the G protein-coupled CCK-B/gastrin receptor. (PMID:17889508)
• The data suggest that protein kinase C contributes to the phosphorylation of influenza PB1 and NS1 proteins which appears to be functionally relevant for both viral RNA polymerase activity and efficient viral replication. (PMID:19264651)
• Data demonstrate the functional role of protein kinase D1 and protein kinase D3 in modulating physiological responses to Ox1R activation. (PMID:20621130)
• PKD3 may contribute to the malignant progression of prostate cancer cells through negative regulation of MMP-7 expression. (PMID:20813660)
• PKD3 contributes to the proliferation and malignant growth of androgen-dependent prostate cancer cells in part by upregulating PSA expression. (PMID:20813663)
• phosphorylation of GIT1 on serine 46 by PKD3 represents a molecular switch by which GIT1 localization, paxillin trafficking, and cellular protrusive activity are regulated. (PMID:22893698)
• PKD antagonists inhibited differentiation and viability of human hematopoietic stem cells, and had less HDAC phosphorylation, confirming the need for PKD-HDAC signaling in erythropoiesis. (PMID:22983445)
• We have identified PKD2 and PKD3, especially PKD3, as novel cell growth regulators in HCC1806 triple-negative breast cancer cells (PMID:23393329)
• PKD3 negatively regulates human airway epithelial barrier formation and integrity through down-regulation of claudin-1, which is a key component of tight junctions. (PMID:24265314)
• PKD3 in TNBC cells provides a molecular connection between the Golgi and endolysosomal compartments to enhance proliferative mTORC1-S6K1 signaling. (PMID:24337579)
• Activation of PKD2 and further increase of PKD3 activity leads to additional phosphorylation and inhibition of endogenous phosphatase slingshot 1L. (PMID:24840177)
• for the first time, PKD3 is implicated in the transcription activation of latent HIV-1 provirus, and our results revealed a molecular mechanism of prostratin-induced HIV-1 transcription via PKCepsilon/PKD3/NF-kappaB signaling pathway. (PMID:25136641)
• Loss of PKD2 enhanced KC proliferative potential while loss of PKD3 resulted in a progressive proliferation defect, loss of clonogenicity and diminished tissue regenerative ability. (PMID:25802335)
• Studies indicate that the loss of protein kinase D PKD1 is thought to promote invasion and metastasis, while PKD2 and upregulated PKD3 to be positive regulators of proliferation. (PMID:26253275)
• None of the Polymorphous low-grade adenocarcinoma (PLGA) lacking PRKD1 somatic mutations or PRKD gene family rearrangements harboured somatic mutations in the kinase domains of the PRKD2 or PRKD3 genes. (PMID:26426580)
• This study discovered and characterized a novel, highly conserved N-terminal domain, comprising 92 amino acids, which mediates dimerization of Protein Kinase D (PKD) isoforms, PKD1, PKD2, and PKD3 monomers. (PMID:27662904)
• Our findings suggest that abnormal PKD3 expression might contribute to hepatocellular carcinoma progression. Furthermore, high PKD3 expression predicts a poor prognosis in hepatocellular carcinoma patients after hepatectomy (PMID:28363424)
• The enriched pathway analysis reveals that PRKD3 regulates pathways contributing to multiple cancer related events, including cell cycle, migration and others. (PMID:28656000)
• KD2 and PKD3 were the two major isoforms of PKD overexpressed in breast cancer. Suppressing either PKD2 or PKD3 was able to reduce breast cancer cell proliferation and metastasis. (PMID:30652415)
• exogenous SCF, CCL5 and CCL11 reversed the effect on MCs migration inhibited by PKD2/3 silencing. Mechanistically, PKD2/3 interacted with Erk1/2 and activated Erk1/2 or NF-kappaB signaling pathway, leading to AP-1 or NF-kappaB binding to the promoter of scf, ccl5 and ccl11. (PMID:30841931)
• The PRKD3 up-regulated 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and activated glycolysis as shown by increased glucose consumption and lactate production. (PMID:31026442)
• The GEF-H1/PKD3 signaling pathway promotes the maintenance of triple-negative breast cancer stem cells. (PMID:31745977)
• Protein Kinase D3 promotes the cell proliferation by activating the ERK1/c-MYC axis in breast cancer. (PMID:31944568)
• Deletion of Protein Kinase D3 Promotes Liver Fibrosis in Mice. (PMID:32048304)
• Protein kinase D3 regulates the expression of the immunosuppressive protein, PDL1, through STAT1/STAT3 signaling. (PMID:32319563)
• PRKD3 promotes malignant progression of OSCC by downregulating KLF16 expression. (PMID:33378018)
• Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration. (PMID:36672148)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkd3	ENSDARG00000079967
mus_musculus	Prkd3	ENSMUSG00000024070
rattus_norvegicus	Prkd3	ENSRNOG00000005289
drosophila_melanogaster	PKD	FBGN0038603
caenorhabditis_elegans		WBGENE00011254
caenorhabditis_elegans		WBGENE00018620
caenorhabditis_elegans		WBGENE00018621

Paralogs (2): PRKD2 (ENSG00000105287), PRKD1 (ENSG00000184304)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1922542) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal trabecular bone morphology	1
abnormal vertebrae morphology	1
abnormal femur morphology	1
impaired glucose tolerance	1
increased circulating aspartate transaminase level	1
abnormal retina blood vessel morphology	1
preweaning lethality, incomplete penetrance	1
decreased total retina thickness	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	A6N9I4	96.7%	Diamond
Xenopus laevis	Q32N25	95.6%	Diamond
Xenopus tropicalis	A4IJ06	95.2%	Diamond
Mesocricetus auratus	Q64398	94.2%	Diamond
Caenorhabditis briggsae	A8XWC4	84.3%	Diamond
Aspergillus niger CBS 513.88	A2QIL5	67.8%	Diamond
Dictyostelium discoideum	Q55CY9	62.2%	Diamond
Schizosaccharomyces pombe 972h-	Q09746	53.7%	Diamond
Aspergillus nidulans FGSC A4	P0C1B1	49.2%	Diamond
Toxoplasma gondii ME49	S8G6L4	42.8%	Diamond
Saccharomyces cerevisiae S288C	P39009	40.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CEBPZOS	protein-coding	100505876
CEBPZ	protein-coding	10153
GPATCH11	protein-coding	253635
SULT6B1	protein-coding	391365
NDUFAF7	protein-coding	55471
EIF2AK2	protein-coding	5610
PRKD3-DT	ncRNA	101929542
QPCT	protein-coding	25797

Protein

Protein identifiers

Serine/threonine-protein kinase D3 — O94806 (reviewed: O94806)

Alternative names: Protein kinase C nu type, Protein kinase EPK2, nPKC-nu

All UniProt accessions (4): C9JKP8, H0Y5M6, H7C172, O94806

UniProt curated annotations — full annotation on UniProt →

Function. Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. Involved in resistance to oxidative stress.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Ubiquitous.

Activity regulation. Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domains 1 and 2 bind both DAG and phorbol ester with high affinity and mediate translocation to the cell membrane. Autophosphorylation of Ser-735 and phosphorylation of Ser-731 by PKC relieves auto-inhibition by the PH domain.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O94806-1	1	yes
O94806-2	2

RefSeq proteins (1): NP_005804* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001849	PH_domain	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015727	Protein_Kinase_C_mu-related	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020454	DAG/PE-bd	Domain
IPR046349	C1-like_sf	Homologous_superfamily
IPR057764	Ubiquitin_PRKD1-3_N	Domain

Pfam: PF00069, PF00130, PF00169, PF25525

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)

• 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 (52 total): modified residue 18, mutagenesis site 8, sequence variant 6, strand 6, domain 2, splice variant 2, zinc finger region 2, turn 2, binding site 2, chain 1, region of interest 1, helix 1, active site 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
2D9Z	Solution structure of the PH domain of Protein kinase C, nu type from human	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94806-F1	69.57	0.26

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, CAMK Ser/Thr protein kinases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane; basal body; nucleoplasm; vesicles

Antibody reliability (HPA): IH uncertain · IF supported

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)

Position	Role
699	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
582–590	ATP
605	ATP

Post-translational modifications (18)

Type	Positions
Phosphoserine	27, 37, 41, 44, 213, 216, 364, 391, 395, 442, 539, 731, 735, 6
Phosphotyrosine	426, 457, 742
Phosphothreonine	535

Mutagenesis-validated functional residues (8)

Position	Phenotype
156	slight loss in ability to bind dag and phorbol-ester; when associated with f-158.
158	slight loss in ability to bind dag and phorbol-ester; when associated with a-156.
165	no effect on ability to bind phorbol ester, loss of ability to bind dag, reduced dag-induced membrane translocation.
166	slight loss in ability to bind dag and phorbol-ester.
170	slight loss in ability to bind dag and phorbol-ester.
282	no effect on ability to bind phorbol ester, increase in ability to bind dag.
284	slight increase in ability to bind dag, no effect on phorbol-ester binding.
293	increased ability to bind dag, no effect on phorbol-ester binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-1660661	Sphingolipid de novo biosynthesis	—
R-HSA-428157	Sphingolipid metabolism	—

MSigDB gene sets: 258 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, VICENT_METASTASIS_UP, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, YANG_BREAST_CANCER_ESR1_LASER_DN, BROWNE_HCMV_INFECTION_16HR_UP, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_2NM_UP, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_2_UP, BROWNE_HCMV_INFECTION_48HR_DN, MARTINEZ_RB1_TARGETS_UP, MODULE_289, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN

GO Biological Process (4): protein phosphorylation (GO:0006468), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), sphingolipid biosynthetic process (GO:0030148), intracellular signal transduction (GO:0035556)

GO Molecular Function (12): protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), diacylglycerol-dependent, calcium-independent serine/threonine kinase activity (GO:0004699), ATP binding (GO:0005524), zinc ion binding (GO:0008270), kinase activity (GO:0016301), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

28 GO namespaces:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
protein kinase activity	2
phosphorylation	1
protein modification process	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
sphingolipid metabolic process	1
lipid biosynthetic process	1
signal transduction	1
protein serine/threonine kinase activity	1
diacylglycerol-dependent serine/threonine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
transition metal ion binding	1
transferase activity, transferring phosphorus-containing groups	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
membrane	1
cell periphery	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
cytosol	CC	direct assay
plasma membrane	CC	direct assay
kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 930 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKD3	PLEK2	Q9NYT0	752
PRKD3	PLEK	P08567	751
PRKD3	OSBP	P22059	591
PRKD3	KIDINS220	Q9ULH0	586
PRKD3	PI4KB	P78405	584
PRKD3	HDAC5	Q9UQL6	570
PRKD3	CERT1	Q9Y5P4	566
PRKD3	SSH1	Q8WYL5	504
PRKD3	VAPA	Q9P0L0	479
PRKD3	AKAP10	O43572	429
PRKD3	HDAC9	Q9UKV0	429
PRKD3	CALML4	Q96GE6	425
PRKD3	NFKBIA	P25963	413
PRKD3	CALML5	Q9NZT1	405
PRKD3	CALML6	Q8TD86	404

IntAct

Human interaction partners of PRKD3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
PRKD2	association	0.730	1
PRKD1	association	0.640	2
VAMP2	physical association	0.620	7
PKM	phosphorylation reaction	0.440	1
DLAT	physical association	0.370	1
NUDT3	physical association	0.370	1
SKA2	physical association	0.370	1
NDUFA4	association	0.350	1
MYH3	physical association	0.000	1
TAF1	physical association	0.000	1

BioGRID (63 interactions; top human partners by supporting records): PRKD2 (Affinity Capture-MS; 6 records), PRKD1 (Affinity Capture-MS; 3 records), RAB7A (Proximity Label-MS; 2 records), ALDH5A1 (Affinity Capture-MS), ANXA5 (Affinity Capture-MS), ASB11 (Proximity Label-MS), ATAD3B (Affinity Capture-MS), ATP5O (Affinity Capture-MS), BCL6 (Affinity Capture-MS), DLAT (Two-hybrid), EXTL3 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), FUCA1 (Affinity Capture-MS), HDAC2 (Affinity Capture-MS), HDAC5 (Affinity Capture-MS)

SIGNOR signaling

showing 7 of 11 signaling interactions:

A	Effect	B	Mechanism
PRKD3	unknown	GIT1	phosphorylation
PKA	“up-regulates activity”	PRKD3	phosphorylation
PRKD3	“up-regulates activity”	HDAC5	phosphorylation
PRKD3	“up-regulates activity”	PAK4	phosphorylation
PRKD3	“up-regulates activity”	HDAC7	phosphorylation
PRKD3	“down-regulates activity”	SSH1	phosphorylation
PRKD3	“up-regulates activity”	MFF	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for PRKD3: 84 ClinVar records (0 pathogenic / likely pathogenic); 14 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	2
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 44 predictions of 2,383):

Position(s)	Effect	Δscore	Sites
2:37254202–37254203	donor_loss	1.0000	5
2:37254290–37254291	acceptor_loss	1.0000	4
2:37267428–37267429	donor_loss	1.0000	6
2:37269613–37269614	donor_loss	1.0000	4
2:37269688–37269689	acceptor_loss	1.0000	6
2:37272378–37272379	donor_loss	1.0000	5
2:37272433–37272434	acceptor_loss	1.0000	6
2:37272435	acceptor_gain	1.0000
2:37272440–37272442	acceptor_gain	1.0000	2
2:37279744–37279745	donor_loss	1.0000	5

AlphaMissense

3,014 missense substitutions predicted likely pathogenic (of 5,901 scored), across 597 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M652	9	0.990	1.000
M641	9	0.940	0.994
M401	9	0.923	0.985
M174	9	0.920	0.999
M659	9	0.908	0.997
M792	9	0.904	0.997
M759	9	0.880	0.998
D699	8	1.000	1.000
N704	8	1.000	1.000
D720	8	1.000	1.000
D758	8	1.000	1.000
H193	8	0.999	1.000
H310	8	0.999	1.000
H697	8	0.999	1.000
H272	8	0.998	1.000
D658	8	0.998	1.000
H155	8	0.997	0.999
H691	8	0.997	1.000
F721	8	0.997	1.000
F774	8	0.997	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Chromophobe (TCGA)	unfavorable	4.5e-06
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000712

Disease associations

OMIM: gene MIM:607077 | disease phenotypes:

GWAS associations

14 associations:

Study	Trait	p-value
GCST90002389_328	Lymphocyte percentage of white cells	2e-12
GCST004904_63	Body mass index	3e-12
GCST004279_30	Systolic blood pressure	7e-11
GCST007099_45	Systolic blood pressure	1e-10
GCST006979_1017	Heel bone mineral density	4e-10
GCST90002399_302	Neutrophil percentage of white cells	4e-10
GCST012182_14	Alzheimer’s disease	1e-9
GCST004904_44	Body mass index	3e-9
GCST002149_12	Schizophrenia	7e-9
GCST011769_2	Schizophrenia	9e-9
GCST004146_1	Chronic lymphocytic leukemia	5e-8
GCST007096_22	Pulse pressure	5e-8
GCST007094_94	Diastolic blood pressure	1e-6
GCST002299_6	Chronic lymphocytic leukemia	9e-6

EFO canonical traits (from GWAS)

7 canonical traits:

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0004340	body mass index
EFO:0009270	heel bone mineral density
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2096620 (PROTEIN FAMILY), CHEMBL2595 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 540,020 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 62 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3301610	ABEMACICLIB	4	7,497
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL2325741	CAPIVASERTIB	4	2,281
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL2028663	DABRAFENIB	4	13,060
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL31	GATIFLOXACIN	4	25,411
CHEMBL939	GEFITINIB	4	119,425
CHEMBL1863513	INGENOL MEBUTATE	4	1,527
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL1078178	MOMELOTINIB	4	3,649
CHEMBL180022	NERATINIB	4	9,891
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL189963	PALBOCICLIB	4	13,796
CHEMBL535	SUNITINIB	4	80,232
CHEMBL83	TAMOXIFEN	4	173,287
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL2105728	CRENOLANIB	3	2,278
CHEMBL522892	DOVITINIB	3	5,162
CHEMBL38380	FASUDIL	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL265502	SURAMIN	3
CHEMBL1976040	ADAVOSERTIB	2
CHEMBL495727	AT-9283	2
CHEMBL513909	BI-2536	2
CHEMBL3545396	BMS-690514	2
CHEMBL1614713	CC-401	2
CHEMBL1967878	CENISERTIB	2
CHEMBL28509	EDELFOSINE	2
CHEMBL1230609	FORETINIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL564829	MILCICLIB	2
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2
CHEMBL475251	R-406	2
CHEMBL565612	SOTRASTAURIN	2
CHEMBL1721885	SU-014813	2
CHEMBL363648	TAK-715	2
CHEMBL230011	TG100-115	2
CHEMBL574737	UCN-01	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL1090090	VX-702	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL2140408	AMG-900	1
CHEMBL574738	AST-487	1
CHEMBL2041933	AZD-7762	1
CHEMBL296468	BMS-387032	1
CHEMBL482967	CYC-116	1
CHEMBL1090479	GSK-1070916	1
CHEMBL1908394	GSK-461364	1
CHEMBL494089	GSK-690693	1
CHEMBL1908397	KW-2449	1
CHEMBL49120	PD-0166285	1
CHEMBL1084546	PF-00562271	1
CHEMBL3128043	PF-03758309	1
CHEMBL4289017	PF-03814735	1
CHEMBL1230607	PHA-793887	1
CHEMBL1230122	R-1487	1
CHEMBL3545083	RGB-286638	1
CHEMBL3545328	XL-019	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Protein kinase D (PKD) family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
BPKDi	Inhibition	9.0	pIC50
CRT 0066101	Inhibition	8.7	pIC50

Binding affinities (BindingDB)

263 measured of 421 human assays (439 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
CHEMBL4528495	IC50	0.15 nM
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
CHEMBL6144731	KD	0.18 nM
CHEMBL3741746	EC50	0.19 nM
CHEMBL4435580	IC50	0.22 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
AP-26113	IC50	0.37 nM
CHEMBL4587471	EC50	0.55 nM
CHEMBL4575056	EC50	0.6 nM
CHEMBL5440043	IC50	1 nM
CHEMBL5419827	IC50	1 nM
CHEMBL5428541	IC50	1 nM
Compound K-252a(epi)	IC50	1.2 nM
Staurosporine	KD	1.7 nM
CHEMBL83790	IC50	2.2 nM
corilagin	EC50	3.2 nM
CEP-701	KD	3.4 nM
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	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
Staurosporine, 8	IC50	6.5 nM
NB-506 Analogue	EC50	8 nM
Momelotinib	IC50	8 nM	US-9469613: (N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide
CHEMBL329274	IC50	10 nM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	KI	15 nM	US-10981896: Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase
CHEMBL1240703	KD	15 nM
CHEMBL4441825	IC50	16 nM
CHEMBL4515390	IC50	16 nM
NB-506 Analogue	EC50	17 nM
2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide	IC50	17 nM
(Rebeccamycin)1,11-dichloro-12-(3,4-dihydroxy-6-hydroxymethyl-5-methoxytetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	IC50	19 nM
NB-506 Analogue	EC50	20 nM
NB-506 Analogue	EC50	25 nM
NB-506 Analogue	EC50	26 nM
CHEMBL147986	IC50	28 nM
NB-506 Analogue	EC50	30 nM
UCN-01	IC50	30 nM
NB-506 Analogue	EC50	32 nM
CHEMBL4787572	IC50	35 nM
2,9-dihydroxy-6-(2-hydroxy-1-hydroxymethylethylamino)-13-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	37 nM
CHEMBL140600	IC50	38 nM
NB-506 Analogue	EC50	40 nM
NB-506 Analogue	EC50	42 nM
CHEMBL421947	IC50	50 nM
CHEMBL4790321	IC50	50 nM
2,10-dihydroxy-6-(2-hydroxy-1-hydroxymethylethylamino)-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	51 nM
Edotecarin	EC50	51 nM
2,9-dihydroxy-6-(2-hydroxy-1-hydroxymethylethylamino)-12-(3,4,5-trihydroxy-6-hydroxymethyltetrahydro-2H-2-pyranyl)-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione	EC50	55 nM

ChEMBL bioactivities

780 potent at pChembl≥5 of 887 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	STAUROSPORINE
10.05	IC50	0.09	nM	CHEMBL4442196
9.89	IC50	0.13	nM	CHEMBL3741746
9.85	IC50	0.14	nM	CHEMBL4575056
9.82	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
9.66	IC50	0.22	nM	CHEMBL4435580
9.44	IC50	0.36	nM	CHEMBL4587471
9.26	EC50	0.55	nM	CHEMBL4587471
9.22	EC50	0.6	nM	CHEMBL4575056
9.22	IC50	0.6	nM	STAUROSPORINE
9.00	IC50	1	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL5440043
8.83	IC50	1.49	nM	STAUROSPORINE
8.82	IC50	1.52	nM	STAUROSPORINE
8.82	IC50	1.5	nM	CHEMBL5419827
8.77	IC50	1.7	nM	CHEMBL291126
8.70	IC50	2	nM	CHEMBL162621
8.70	IC50	2	nM	STAUROSPORINE
8.70	IC50	2	nM	CHEMBL5428541
8.68	IC50	2.07	nM	STAUROSPORINE
8.68	IC50	2.1	nM	SOTRASTAURIN
8.66	IC50	2.2	nM	CHEMBL83790
8.57	IC50	2.7	nM	STAUROSPORINE
8.52	IC50	3	nM	STAUROSPORINE
8.52	Kd	3	nM	CHEMBL400402
8.40	Ki	3.981	nM	CHEMBL1986263
8.40	Ki	3.981	nM	CHEMBL1997129
8.40	Ki	3.981	nM	CHEMBL1974870
8.40	Ki	3.981	nM	CHEMBL1991063
8.39	IC50	4.1	nM	UCN-01
8.34	IC50	4.6	nM	CHEMBL6144731
8.30	IC50	5	nM	CHEMBL538718
8.30	Ki	5.012	nM	CHEMBL1994669
8.30	Ki	5.012	nM	CHEMBL1970903
8.30	Ki	5.012	nM	CHEMBL1973720
8.30	Ki	5.012	nM	CHEMBL2005509
8.28	Ki	5.3	nM	BALANOL
8.22	IC50	6	nM	CHEMBL4515390
8.22	Kd	6	nM	CHEMBL27768
8.22	IC50	6	nM	STAUROSPORINE
8.20	Ki	6.31	nM	CHEMBL1966628
8.20	Ki	6.31	nM	CHEMBL2001751
8.19	IC50	6.5	nM	STAUROSPORINE
8.15	IC50	7	nM	STAUROSPORINE
8.12	IC50	7.5	nM	STAUROSPORINE
8.10	IC50	8	nM	STAUROSPORINE
8.10	IC50	7.9	nM	STAUROSPORINE

PubChem BioAssay actives

243 with measured affinity, of 2459 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-12-benzoyloxy-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-22-acetyloxy-12-benzoyloxy-10,11-dihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] naphthalene-2-carboxylate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,25R)-12-benzoyloxy-10,11-dihydroxy-9-(hydroxymethyl)-13,15-dimethyl-22-oxo-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	165147: Inhibition Protein kinase C (PKC)	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] 4-nitrobenzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-12-benzoyloxy-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-propan-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] 4-methoxybenzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(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
2-piperazin-1-yl-6-(2-piperidin-1-yl-4-pyridinyl)pyridine-4-carboxamide	1964578: Inhibition of PKD3 (unknown origin)	ic50	0.0010	uM
3-[6-amino-5-(6-ethoxynaphthalen-2-yl)-3-pyridinyl]-N-[2-(dimethylamino)ethyl]benzamide	1964578: Inhibition of PKD3 (unknown origin)	ic50	0.0015	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
2-[4-[[(2S)-2-aminobutyl]amino]pyrimidin-2-yl]-4-(1-methylpyrazol-4-yl)phenol	1964578: Inhibition of PKD3 (unknown origin)	ic50	0.0020	uM
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	1902442: Inhibition of PKCnu (unknown origin) by IMAP kinase assay	ic50	0.0021	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1425137: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0030	uM
(17S,20S)-28-dimethylphosphoryl-13,13-difluoro-11,16-dimethyl-25-(trifluoromethyl)-4,11,16,21,23,26-hexazapentacyclo[20.3.1.15,9.117,20.02,6]octacosa-1(26),2,5,7,9(28),22,24-heptaen-10-one	2225532: Inhibition of PRKD3 (unknown origin)	ic50	0.0046	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
2-[4-[[(2R)-2-aminobutyl]amino]pyrimidin-2-yl]-4-(1-methylpyrazol-4-yl)phenol	1742911: Inhibition of recombinant FLAG-tagged PKD3 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay	ic50	0.0060	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
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-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-nonaen-3-one	508049: Binding affinity to PRKD3	kd	0.0089	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
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-(1H-indol-3-yl)-1-(piperidin-4-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-amine	1742911: Inhibition of recombinant FLAG-tagged PKD3 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay	ic50	0.0170	uM
N-[(1R)-1-cyanoethyl]-3-[5-[4-[(oxan-4-ylamino)methyl]phenyl]-1,2-oxazol-3-yl]benzamide	580272: Inhibition of human PKD3	ic50	0.0170	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-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
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-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-16-carboxylate	1425137: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0380	uM
3-(2-ethoxyquinolin-6-yl)-1-[(1-methylpiperidin-4-yl)methyl]pyrazolo[3,4-d]pyrimidin-4-amine	1742911: Inhibition of recombinant FLAG-tagged PKD3 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay	ic50	0.0430	uM
(10S,13S)-13-(hydroxymethyl)-9-methyl-10-propan-2-yl-3,9,12-triazatricyclo[6.6.1.04,15]pentadeca-1,4(15),5,7-tetraen-11-one	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	0.0470	uM
9-hydroxy-3,4-dihydro-2H-[1]benzothiolo[2,3-f][1,4]thiazepin-5-one	1964578: Inhibition of PKD3 (unknown origin)	ic50	0.0530	uM
10-hydroxy-2,3,4,5-tetrahydro-[1]benzothiolo[3,2-b][1,5]thiazocin-6-one	1799562: In Vitro Radiometric Kinase Assay from Article 10.1186/1472-6769-10-5: “Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility.”	ic50	0.0588	uM
N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-3-methylbutanamide	1425137: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0650	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149084: Binding affinity to human PRKD3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0724	uM
[(1S,4S,5S,6R,9S,10R,12R,14R)-5,6-dihydroxy-7-(hydroxymethyl)-3,11,11,14-tetramethyl-15-oxo-4-tetracyclo[7.5.1.01,5.010,12]pentadeca-2,7-dienyl] (Z)-2-methylbut-2-enoate	1459482: Activation of PKC in human platelet assessed as induction of platelet aggregation measured within 15 mins by tribidimetric method	ec50	0.0725	uM
3-[4-amino-3-(1H-indol-3-yl)pyrazolo[3,4-d]pyrimidin-1-yl]-2,2-dimethylpropan-1-ol	1742911: Inhibition of recombinant FLAG-tagged PKD3 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay	ic50	0.0760	uM
3-naphthalen-1-yl-1-(piperidin-4-ylmethyl)pyrazolo[3,4-d]pyrimidin-4-amine	1742911: Inhibition of recombinant FLAG-tagged PKD3 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay	ic50	0.0780	uM
bis(3,3-bis[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-2-phenylprop-2-enenitrile);pentahydrochloride	1323681: Inhibition of PKC in human SH-SY5Y cells assessed as inhibition of PMA-stimulated MARCKS phosphorylation preincubated for 1 hr followed by PMA-stimulation for 15 mins by Western blot analysis	ic50	0.0800	uM
3-hydroxy-2-[4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]benzoic acid	254303: Inhibitory activity against protein kinase C	ki	0.0800	uM
3,13-diazahexacyclo[14.8.0.02,10.04,9.011,15.017,22]tetracosa-1(16),2(10),4,6,8,11(15),17,19,21-nonaene-12,14-dione	277640: Inhibition of PKC	ic50	0.0830	uM
3-[3-(2-piperidin-1-ylethoxy)phenyl]-5-(1H-1,2,4-triazol-5-yl)-1H-indazole	1425137: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0900	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625024: Binding constant for PRKD3 kinase domain	kd	0.0900	uM
9-hydroxy-10-iodo-3,4-dihydro-2H-[1]benzothiolo[2,3-f][1,4]thiazepin-5-one	1799562: In Vitro Radiometric Kinase Assay from Article 10.1186/1472-6769-10-5: “Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility.”	ic50	0.0911	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425137: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0930	uM
5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)-N-[(3S,4S,6S)-4-(3,4-difluorophenyl)-6-[2-(methylamino)-2-oxoethyl]piperidin-3-yl]furan-2-carboxamide	1608042: Inhibition of PKC (unknown origin)	ic50	0.0940	uM
Brigatinib	2182828: Inhibition of human PRKD3 using KKLNRTLSVA as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.0950	uM
9-methoxy-3,4-dihydro-2H-[1]benzothiolo[2,3-f][1,4]thiazepin-5-one	1799562: In Vitro Radiometric Kinase Assay from Article 10.1186/1472-6769-10-5: “Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility.”	ic50	0.0985	uM
(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-3-hydroxy-2-[3-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]propanoylamino]propanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoic acid	164148: Displacement of ATP from protein kinase C (PKC)	ki	0.1000	uM
Momelotinib	2183877: Inhibition of PRKCN (unknown origin)	ic50	0.1000	uM
1-tert-butyl-3-naphthalen-1-ylpyrazolo[3,4-d]pyrimidin-4-amine	1964578: Inhibition of PKD3 (unknown origin)	ic50	0.1040	uM
2-(5-chloro-2-fluorophenyl)-N-pyridin-4-ylpteridin-4-amine	1964578: Inhibition of PKD3 (unknown origin)	ic50	0.1050	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	5
Acetaminophen	decreases expression, affects cotreatment, increases expression	2
Arsenic	increases response to substance, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
coumarin	increases phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
asparanin A	decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Carbamazepine	affects expression	1
Catechin	affects cotreatment, increases expression	1
Chenodeoxycholic Acid	affects cotreatment, increases expression	1
Cisplatin	increases expression	1
Deoxycholic Acid	affects cotreatment, increases expression	1
Diclofenac	affects expression	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Glycochenodeoxycholic Acid	increases expression, affects cotreatment	1

ChEMBL screening assays

557 unique, capped per target: 546 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

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

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

Cellosaurus	Name	Category	Sex
CVCL_B2C7	Abcam HeLa PRKD3 KO	Cancer cell line	Female
CVCL_D7YP	Ubigene A-549 PRKD3 KO	Cancer cell line	Male
CVCL_D8U2	Ubigene HCT 116 PRKD3 KO	Cancer cell line	Male
CVCL_D9PT	Ubigene HEK293 PRKD3 KO	Transformed cell line	Female
CVCL_E0M0	Ubigene HeLa PRKD3 KO	Cancer cell line	Female
CVCL_TH00	HAP1 PRKD3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PRKD3 across ~30M SureChEMBL compounds — explore on Sugi Predict.