SMYD3

Summary

SMYD3 (SET and MYND domain containing 3, HGNC:15513) is a protein-coding gene on chromosome 1q44, encoding Histone-lysine N-methyltransferase SMYD3 (Q9H7B4). Histone methyltransferase.

This gene encodes a histone methyltransferase which functions in RNA polymerase II complexes by an interaction with a specific RNA helicase. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 64754 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 111 total
• Druggable target: yes
• MANE Select transcript: NM_001167740

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15513
Approved symbol	SMYD3
Name	SET and MYND domain containing 3
Location	1q44
Locus type	gene with protein product
Status	Approved
Aliases	KMT3E
Ensembl gene	ENSG00000185420
Ensembl biotype	protein_coding
OMIM	608783
Entrez	64754

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding_CDS_not_defined, 6 protein_coding, 1 retained_intron

ENST00000366516, ENST00000366517, ENST00000391836, ENST00000403792, ENST00000453676, ENST00000455277, ENST00000462422, ENST00000464398, ENST00000470510, ENST00000470863, ENST00000482592, ENST00000483072, ENST00000488153, ENST00000490107, ENST00000490322, ENST00000492487, ENST00000493441, ENST00000630181

RefSeq mRNA: 6 — MANE Select: NM_001167740 NM_001167740, NM_001375962, NM_001375963, NM_001375965, NM_001375966, NM_022743

CCDS: CCDS31083, CCDS53486

Canonical transcript exons

ENST00000490107 — 12 exons

Exon	Start	End
ENSE00002067094	246507054	246507279
ENSE00003683086	246355031	246355094
ENSE00003777951	245858496	245858670
ENSE00003779374	245929870	245929937
ENSE00003779817	245927931	245928033
ENSE00003780541	246330480	246330537
ENSE00003781031	246327201	246327337
ENSE00003781340	246335367	246335474
ENSE00003782765	245915530	245915640
ENSE00003783154	245764041	245764149
ENSE00003783526	245863799	245863886
ENSE00003848550	245749347	245749664

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 93.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.6352 / max 485.4285, expressed in 1799 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18478	15.8232	1792
18474	2.4501	350
18428	1.1946	92
18479	0.6553	361
18472	0.1636	77
18473	0.0890	49
18452	0.0772	39
18471	0.0518	22
18454	0.0340	16
18464	0.0280	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	93.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.09	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.79	gold quality
stromal cell of endometrium	CL:0002255	91.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.18	gold quality
cortical plate	UBERON:0005343	89.72	gold quality
prefrontal cortex	UBERON:0000451	89.44	gold quality
adrenal tissue	UBERON:0018303	89.10	gold quality
calcaneal tendon	UBERON:0003701	88.92	gold quality
cerebellar cortex	UBERON:0002129	88.31	gold quality
cerebellar hemisphere	UBERON:0002245	88.24	gold quality
colonic epithelium	UBERON:0000397	88.15	gold quality
ganglionic eminence	UBERON:0004023	88.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.07	gold quality
left lobe of thyroid gland	UBERON:0001120	87.79	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.62	gold quality
left adrenal gland cortex	UBERON:0035825	87.59	gold quality
left adrenal gland	UBERON:0001234	87.58	gold quality
anterior cingulate cortex	UBERON:0009835	87.58	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.55	gold quality
cerebellum	UBERON:0002037	87.48	gold quality
right frontal lobe	UBERON:0002810	87.47	gold quality
cingulate cortex	UBERON:0003027	87.44	gold quality
right adrenal gland cortex	UBERON:0035827	87.37	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.25	gold quality
right adrenal gland	UBERON:0001233	87.09	gold quality
thyroid gland	UBERON:0002046	87.01	gold quality
frontal cortex	UBERON:0001870	87.00	gold quality
right lobe of thyroid gland	UBERON:0001119	86.97	gold quality
neocortex	UBERON:0001950	86.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

11 targeting SMYD3, 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-3910	99.95	71.13	2227
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-346	97.01	66.97	662

Literature-anchored findings (GeneRIF, showing 40)

• SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. (PMID:15235609)
• SMYD3-NY is a novel transcript variant of the SMYD3 gene, and SMYD3-NY protein may influence transcriptional regulation during spermatogenesis via HTMase activity (PMID:16081583)
• The common variable number of tandem repeats polymorphism in SMYD3 is a susceptibility factor for some types of human cancer. (PMID:16155568)
• Enhanced SMYD3 expression is associated with growth of breast cancer (PMID:16441421)
• study shows that SMYD3 polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in Chinese population (PMID:17431393)
• The proliferation, migration induction and apoptosis inhibition activities of SMYD3 in hepatocellular carcinoma may be mediated through RIZ1 CpG promoter hypermethylation. (PMID:17963297)
• A cleaved form lacking the amino-terminal 34 amino acids is higher in methyltransferase activity in cancer cells. (PMID:17998933)
• data indicate that the SMYD3 genotype is not related to the risk of developing NSCLC (PMID:18027872)
• VNTR polymorphism in the promoter region of SMYD3 gene may be a susceptibility factor for human cancers such as ESCC by interacting with tobacco carcinogens. (PMID:18294291)
• SMYD3 plays crucial roles in HeLa cell proliferation and migration/invasion, and that it may be a useful therapeutic target in human cervical carcinomas. (PMID:18452649)
• SMYD3 has a role in regulation of c-Met expression and in cell migration and invasion induced by HGF (PMID:19321255)
• HBx may induce the expression of histone methyltransferase SMYD3, which in turn stimulates cell proliferation and blocks apoptosis in HepG2 cells. (PMID:19403031)
• The results presented here identify SMYD3 as a new coactivator for estrogen receptor-mediated transcription, providing a possible link between SMYD3 overexpression and breast cancer. (PMID:19509295)
• presence of activating KRAS mutations is significantly correlated to an upregulation of 13 genes (adjusted P-value <0.05), among them DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase (PMID:20725992)
• Down-regulation of SMYD3 induces G1-phase cell cycle arrest, indicating the potent induction of apoptosis by SMYD3 knockdown. (PMID:20957523)
• SmyD3 has a two-lobed structure with the substrate binding cleft located at the bottom of a 15-A-deep crevice formed between the N- and C-terminal lobes. (PMID:21167177)
• Structural analysis shows that the previously uncharacterized C-terminal domain of Smyd3 contains a tetratrico-peptide repeat domain which together with the SET and post-SET domains forms a deep, narrow substrate binding pocket. (PMID:21266482)
• HCVc could upregulate the methylation status of the RASSF1A promoter through regulation of SMYD3, and histone methylation may affect the DNA methylation of downstream gene by an unknown mechanism (PMID:21450690)
• The structure revealed an overall compact architecture in which the “split-SET” domain adopts a canonical SET domain fold and closely assembles with a Zn-binding MYND domain and a C-terminal superhelical 9 alpha-helical bundle. (PMID:21779408)
• Results show SMYD3 as an important new regulator of MMP-9 transcription, and provide a molecular link between SMYD3 overexpression and metastatic cancer progression. (PMID:22194464)
• Depletion of Smyd3 leads to diminished cell proliferation in HeLa cell line. (PMID:22419068)
• low miR-124 levels mediated by HCV core protein via DNMT1 promote intrahepatic cholangiocarcinoma cell migration and invasion by targeting SMYD3 (PMID:22819820)
• SMYD3 promotes prostate tumorigenesis and mediates epigenetic upregulation of AR expression. (PMID:24174655)
• Overexpression of SMYD3 promotes MRTF-A-mediated upregulation of MYL9 and migration of MCF-7 breast cancer cells (PMID:24189459)
• The expression profiling revealed in the more aggressive diseases (i.e. occurrence of metastases; persistent disease; disease-related death) a significant increase of EZH2 and SMYD3 gene expression. (PMID:24813658)
• methylation of MAP3K2 by SMYD3 increases MAP kinase signalling and promotes the formation of Ras-driven carcinomas (PMID:24847881)
• Results suggest that high expression of SMYD3 is related to the occurrence of esophageal squamous cell carcinoma. Also, its suppression promoted the expression of RIZ1 suggesting a signal transduction pathway between SMYD3 and RIZ1. (PMID:24993551)
• Mutational analyses revealed that the MYND-domain of SMYD3 and domain III of hepatitis C virus NS5A are required for the interaction. (PMID:25092459)
• role of histone methyltransferase SMYD3 in tumors (PMID:25248712)
• SMYD3-mediated methylation of MAP3K2 increases mutant K-Ras-induced activation of ERK1/2. (Review) (PMID:25382779)
• High SMYD3 and pSTAT3 expressions may indicate poor prognosis of patients with gastric cancer (PMID:25471787)
• SMYD3 performed an important function in the aggressiveness of gastric carcinoma and may act as a promising target for prognostic prediction. (PMID:25472580)
• SMYD3 and MMP-9 may play important roles in tumor invasion, metastasis, and prognosis and could work as promising targets for prognostic prediction in gastric cancer. (PMID:25627005)
• represent the proof of principle that SMYD3 is a druggable target (PMID:25728514)
• Loss of SMYD3-HSP90 interaction leads to SMYD3 mislocalization within the nucleus, thereby losing its chromatin association. This results in reduction of SMYD3-mediated cell proliferation and, potentially, impairment of SMYD3’s oncogenic activity. (PMID:25738358)
• Results support a proto-oncogenic role for SMYD3 in prostate carcinogenesis, mainly due to its methyltransferase enzymatic activity. (PMID:25980436)
• SET and MYND domain-containing protein 3 expression and TGF-beta1 expression in gastric cancer (GC) tissues were significantly and positively correlated. High expression levels of SMYD3 and TGF-beta1 can indicate poor prognoses for GC patients. (PMID:26077602)
• SMYD3 interacts with the human positive coactivator 4 (PC4) and that such interaction potentiates a group of genes whose expression is linked to cell proliferation and invasion. (PMID:26350217)
• A novel HBx-interacting protein, SMYD3, was identified, leading to proposal of a novel mechanism of AP-1 activation in HBV-infected cells. (PMID:26616333)
• SMYD3 physically interacts with the promoter of BCLAF1 and upregulates its expression by accumulating di- and trimethylation of H3K4 at the BCLAF1 locus. SMYD3 overexpression in bladder cancer cells promotes autophagy activation. (PMID:26676636)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	smyd3	ENSDARG00000058050
mus_musculus	Smyd3	ENSMUSG00000055067
rattus_norvegicus	Smyd3	ENSRNOG00000066304
drosophila_melanogaster	Smyd3	FBGN0011566
drosophila_melanogaster	dao	FBGN0028862
drosophila_melanogaster	SmydA-9	FBGN0030102
drosophila_melanogaster	SmydA-5	FBGN0033061
drosophila_melanogaster	Smyd4-1	FBGN0033427
drosophila_melanogaster	Smyd4-2	FBGN0036282
drosophila_melanogaster	CG18213	FBGN0038470
drosophila_melanogaster	SmydA-8	FBGN0053548
caenorhabditis_elegans	set-18	WBGENE00044070

Paralogs (5): SMYD1 (ENSG00000115593), SMYD5 (ENSG00000135632), ZMYND15 (ENSG00000141497), SMYD2 (ENSG00000143499), SMYD4 (ENSG00000186532)

Protein

Protein identifiers

Histone-lysine N-methyltransferase SMYD3 — Q9H7B4 (reviewed: Q9H7B4)

Alternative names: SET and MYND domain-containing protein 3, Zinc finger MYND domain-containing protein 1

All UniProt accessions (5): A8MXR1, B0QZ88, B0QZ99, B0QZA0, Q9H7B4

UniProt curated annotations — full annotation on UniProt →

Function. Histone methyltransferase. Specifically methylates ‘Lys-4’ of histone H3, inducing di- and tri-methylation, but not monomethylation. Also methylates ‘Lys-5’ of histone H4. Plays an important role in transcriptional activation as a member of an RNA polymerase complex. Binds DNA containing 5’-CCCTCC-3’ or 5’-GAGGGG-3’ sequences.

Subunit / interactions. Interacts with HSPCA. Interacts with HELZ. Interacts with POLR2A; the interaction may be indirect and may be mediated by HELZ. Interacts with HSP90AA1; this interaction enhances SMYD3 histone-lysine N-methyltransferase.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in skeletal muscles and testis. Overexpressed in a majority of colorectal and hepatocellular carcinomas.

Activity regulation. Histone methyltransferase activity strongly stimulated by HSPCA.

Similarity. Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H7B4-1	1	yes
Q9H7B4-2	2
Q9H7B4-3	3

RefSeq proteins (5): NP_001161212, NP_001362891, NP_001362892, NP_001362894, NP_073580 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR002893	Znf_MYND	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR025805	Hist-Lys_N-MeTrfase_SMYD3	Family
IPR044420	SMYD3_SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR050869	H3K4_H4K5_MeTrfase	Family

Pfam: PF00856, PF01753

Enzyme classification (BRENDA):

• EC 2.1.1.354 — [histone H3]-lysine4 N-trimethyltransferase (BRENDA: 18 organisms, 22 substrates, 3 inhibitors, 20 Km, 20 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ART(KME1)QTARKSTGGKAPRKQLATKAA-GK-BIOTIN	0.0002–0.002	5
ART(KME2)QTARKSTGGKAPRKQLATKAA-GK-BIOTIN	0.0003–0.004	5
ARTKQTARKSTGGKAPRKQLATKAA-GK-BIOTIN	0.0002–0.0017	5
S-ADENOSYL-L-METHIONINE	0.014–0.9	5

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H(+) (RHEA:60260)

UniProt features (65 total): helix 20, binding site 15, strand 11, turn 8, splice variant 3, modified residue 2, sequence conflict 2, chain 1, domain 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

34 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6P7Z	X-RAY DIFFRACTION	1.19
6PAF	X-RAY DIFFRACTION	1.24
5V37	X-RAY DIFFRACTION	1.42
5CCL	X-RAY DIFFRACTION	1.5
7O2C	X-RAY DIFFRACTION	1.52
3QWP	X-RAY DIFFRACTION	1.53
6P6K	X-RAY DIFFRACTION	1.55
6ZRB	X-RAY DIFFRACTION	1.55
7O2A	X-RAY DIFFRACTION	1.57
7QNR	X-RAY DIFFRACTION	1.57
6O9O	X-RAY DIFFRACTION	1.59
6P6G	X-RAY DIFFRACTION	1.59
7BJ1	X-RAY DIFFRACTION	1.61
7QNU	X-RAY DIFFRACTION	1.64
5XXJ	X-RAY DIFFRACTION	1.69
3PDN	X-RAY DIFFRACTION	1.7
5HQ8	X-RAY DIFFRACTION	1.72
7QLB	X-RAY DIFFRACTION	1.8
8OWO	X-RAY DIFFRACTION	1.8
3RU0	X-RAY DIFFRACTION	1.85
6YUH	X-RAY DIFFRACTION	1.93
7O2B	X-RAY DIFFRACTION	2.03
3MEK	X-RAY DIFFRACTION	2.1
5YJO	X-RAY DIFFRACTION	2.13
5XXG	X-RAY DIFFRACTION	2.14
5HI7	X-RAY DIFFRACTION	2.15
5CCM	X-RAY DIFFRACTION	2.3
5XXD	X-RAY DIFFRACTION	2.31
6IJL	X-RAY DIFFRACTION	2.35
5EX3	X-RAY DIFFRACTION	2.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H7B4-F1	97.36	0.98

Functional residue map

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

Ligand- & substrate-binding residues (15): 75; 83; 87; 124; 132; 181; 205–206; 239; 259; 14–16; 49; 52 …

Post-translational modifications (2): 1, 22

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization

MSigDB gene sets: 211 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MORF_RAD51L3, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_CORTICOSTEROID_STIMULUS, GOBP_RESPONSE_TO_KETONE, MORF_CTSB, MORF_PRKCA, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_RESPONSE_TO_STEROID_HORMONE

GO Biological Process (7): nucleosome assembly (GO:0006334), myotube cell development (GO:0014904), methylation (GO:0032259), establishment of protein localization (GO:0045184), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to dexamethasone stimulus (GO:0071549), chromatin organization (GO:0006325)

GO Molecular Function (12): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), RNA polymerase II complex binding (GO:0000993), RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding (GO:0001162), zinc ion binding (GO:0008270), histone H4 methyltransferase activity (GO:0140939), histone H3K36 dimethyltransferase activity (GO:0140954), histone H3K4 trimethyltransferase activity (GO:0140999), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), histone methyltransferase activity (GO:0042054), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
myotube differentiation	1
striated muscle cell development	1
metabolic process	1
establishment of localization	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cellular response to glucocorticoid stimulus	1
response to dexamethasone	1
cellular response to ketone	1
cellular component organization	1
cis-regulatory region sequence-specific DNA binding	1
RNA polymerase core enzyme binding	1
intronic transcription regulatory region sequence-specific DNA binding	1
transition metal ion binding	1
histone methyltransferase activity	1
histone H3K36 methyltransferase activity	1
histone H3K4 methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
protein methyltransferase activity	1
histone modifying activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2067 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMYD3	HELZ	P42694	946
SMYD3	NKX2-8	O15522	862
SMYD3	HSP90AA1	P07900	835
SMYD3	ESR1	P03372	820
SMYD3	H3-5	Q6NXT2	686
SMYD3	H3C14	Q71DI3	685
SMYD3	H3-7	Q5TEC6	685
SMYD3	H3-3A	P06351	684
SMYD3	H3-4	Q16695	684
SMYD3	H3C1	P02295	683
SMYD3	MAP3K2	Q9Y2U5	681
SMYD3	SETD7	Q8WTS6	671
SMYD3	PRMT6	Q96LA8	655
SMYD3	PRMT8	Q9NR22	655
SMYD3	HSP90AB1	P08238	626

IntAct

57 interactions, top by confidence:

A	B	Type	Score
OSBPL5	NAGLU	psi-mi:“MI:0914”(association)	0.640
ENKD1	SMYD3	psi-mi:“MI:0915”(physical association)	0.560
ZIC1	SMYD3	psi-mi:“MI:0915”(physical association)	0.560
NUP54	SMYD3	psi-mi:“MI:0915”(physical association)	0.560
CSTF2T	SMYD3	psi-mi:“MI:0915”(physical association)	0.560
PKN1	SMYD3	psi-mi:“MI:0915”(physical association)	0.560
MKRN3	SMYD3	psi-mi:“MI:0915”(physical association)	0.560
SHC3	SMYD3	psi-mi:“MI:0915”(physical association)	0.560
SMYD3		psi-mi:“MI:0915”(physical association)	0.550
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
TMA7	SMYD3	psi-mi:“MI:0915”(physical association)	0.400
SMYD3	CAMK2B	psi-mi:“MI:0915”(physical association)	0.370
SMYD3	NDUFAB1	psi-mi:“MI:0915”(physical association)	0.370
NFYB	SMYD3	psi-mi:“MI:0915”(physical association)	0.370
CYP39A1	SMYD3	psi-mi:“MI:0915”(physical association)	0.370
VANGL1	SMYD3	psi-mi:“MI:0915”(physical association)	0.370
CFTR	SMYD3	psi-mi:“MI:0915”(physical association)	0.370
SMYD3	ECE1	psi-mi:“MI:0915”(physical association)	0.370
SMYD3	H3-5	psi-mi:“MI:0915”(physical association)	0.370
SMYD3	TRIT1	psi-mi:“MI:0915”(physical association)	0.370
SMYD3	ZNF57	psi-mi:“MI:0915”(physical association)	0.370
		psi-mi:“MI:0914”(association)	0.350
RCAN3	OBSL1	psi-mi:“MI:0914”(association)	0.350
SMYD3	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
SMYD3	AMY1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (100): HSP90AA1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), HSP90AB3P (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), MAGED4B (Affinity Capture-MS), KDM3B (Affinity Capture-MS), SMYD3 (Affinity Capture-MS), SMYD3 (Co-fractionation), SMYD3 (Co-fractionation), SMYD3 (Affinity Capture-MS), HSP90AB3P (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), SMYD3 (Affinity Capture-MS)

ESM2 similar proteins: A4IFF3, A4IG72, A6QQ71, A7MB11, D3ZQF4, E9PY46, F6PHZ6, O02697, O75344, O95801, P27124, P30416, P48736, P54729, Q02790, Q0P5H9, Q17QZ7, Q1RLX4, Q3UR70, Q3V3E1, Q4U2V3, Q5EA11, Q5F3K0, Q5RBW9, Q5RGL7, Q62018, Q6GM65, Q6GN68, Q6GNY1, Q6GPE5, Q6P3X3, Q7DMA9, Q7ZXV5, Q80SY4, Q86YT6, Q8BTI9, Q8CD92, Q8N0Z6, Q8R3H9, Q8WUH2

Diamond homologs: A3M0J3, A5DQN2, A6ZTB4, A7TPV3, E1C5V0, O74467, O94256, P38890, Q54DL6, Q54R14, Q557F7, Q5A1M3, Q5RGL7, Q6BSV3, Q6C9E7, Q6CX91, Q6FTT0, Q6GPQ4, Q75BF1, Q9CWR2, Q9H7B4, Q9ZUM9, Q54D67, Q557F6, Q9FG08, F4K1J4, Q5UNT8, Q6GMV2, A9CPT4, C3RZA1, D3ZKV9, F1QN74, F1RET2, P97443, Q0P585, Q12529, Q3TYX3, Q4VC12, Q5BJI7, Q5F3V0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

9197 predictions. Top by Δscore:

Variant	Effect	Δscore
1:245863800:C:CA	donor_gain	1.0000
1:245863897:C:CT	acceptor_gain	1.0000
1:245863898:A:T	acceptor_gain	1.0000
1:245915526:ATAC:A	donor_loss	1.0000
1:245915527:TACCT:T	donor_loss	1.0000
1:245915643:G:C	acceptor_gain	1.0000
1:245915651:C:CT	acceptor_gain	1.0000
1:245915651:C:T	acceptor_gain	1.0000
1:245927925:CCTTA:C	donor_loss	1.0000
1:245927927:TTACC:T	donor_loss	1.0000
1:245927929:ACCT:A	donor_gain	1.0000
1:245927930:C:A	donor_loss	1.0000
1:245927930:CCTC:C	donor_gain	1.0000
1:245928029:AGATA:A	acceptor_gain	1.0000
1:245928030:GATA:G	acceptor_gain	1.0000
1:245928031:ATA:A	acceptor_gain	1.0000
1:245928032:TA:T	acceptor_gain	1.0000
1:245928034:C:CC	acceptor_gain	1.0000
1:245929868:ACCT:A	donor_loss	1.0000
1:245929869:CCTG:C	donor_loss	1.0000
1:245929894:T:TA	donor_gain	1.0000
1:245929933:ATCAC:A	acceptor_gain	1.0000
1:245929934:TCAC:T	acceptor_gain	1.0000
1:245929935:CAC:C	acceptor_gain	1.0000
1:245929935:CACC:C	acceptor_gain	1.0000
1:245929936:AC:A	acceptor_gain	1.0000
1:245929936:ACCTG:A	acceptor_loss	1.0000
1:245929937:CC:C	acceptor_gain	1.0000
1:245929938:C:CC	acceptor_gain	1.0000
1:245929938:C:CG	acceptor_loss	1.0000

AlphaMissense

2837 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:245915566:A:C	F259L	0.998
1:245915566:A:T	F259L	0.998
1:245915568:A:G	F259L	0.998
1:245927997:A:C	C212W	0.998
1:246355075:A:G	C62R	0.998
1:245764048:A:G	L393P	0.997
1:245764090:A:G	L379P	0.997
1:245927985:G:C	F216L	0.997
1:245927985:G:T	F216L	0.997
1:245927987:A:G	F216L	0.997
1:245929882:C:T	G196D	0.997
1:246335463:C:A	W80C	0.997
1:246335463:C:G	W80C	0.997
1:246507073:A:G	C49R	0.997
1:245915597:C:G	R249P	0.996
1:245915639:A:T	L235H	0.996
1:246335392:A:G	L104P	0.996
1:246355036:A:G	C75R	0.996
1:246355051:A:C	Y70D	0.996
1:246355051:A:G	Y70H	0.996
1:246355066:A:G	C65R	0.996
1:246355073:G:C	C62W	0.996
1:246355074:C:G	C62S	0.996
1:246355075:A:T	C62S	0.996
1:246507072:C:T	C49Y	0.996
1:245764096:C:T	G377D	0.995
1:245915585:A:G	L253P	0.995
1:245915598:G:T	R249S	0.995
1:245927999:A:G	C212R	0.995
1:245928011:A:G	C208R	0.995

dbSNP variants (sampled 300 via entrez): RS1000002248 (1:246137515 G>A), RS1000010378 (1:246189716 A>G), RS1000011304 (1:246106363 G>C), RS1000011360 (1:246481309 T>C), RS1000013494 (1:246440205 T>C), RS1000016223 (1:245818214 C>A,T), RS1000017257 (1:245805895 T>C), RS1000021176 (1:245984781 A>G), RS1000024684 (1:245757597 C>A,T), RS1000035473 (1:246111993 T>G), RS1000038634 (1:245794836 C>T), RS1000039384 (1:245918860 A>G), RS1000046624 (1:246001574 G>A), RS1000048485 (1:246214176 G>A,C,T), RS1000048810 (1:246398045 A>G)

Disease associations

OMIM: gene MIM:608783 | disease phenotypes: MIM:192350

GenCC curated gene-disease

Mondo (1): VACTERL/vater association (MONDO:0008642)

Orphanet (1): VACTERL/VATER association (Orphanet:887)

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST001762_277	Obesity-related traits	4.000000e-06
GCST001762_770	Obesity-related traits	4.000000e-06
GCST002304_10	Fractional exhaled nitric oxide (childhood)	8.000000e-06
GCST003118_2	Response to serotonin reuptake inhibitors in non-psychotic unipolar depression	6.000000e-06
GCST003262_571	Post bronchodilator FEV1	4.000000e-06
GCST003262_572	Post bronchodilator FEV1	4.000000e-06
GCST003262_573	Post bronchodilator FEV1	4.000000e-06
GCST005831_1	Systemic lupus erythematosus	4.000000e-08
GCST006522_10	Upper eyelid sagging severity	4.000000e-06
GCST006879_25	Blood metabolite levels	9.000000e-16
GCST008103_176	Bipolar disorder	8.000000e-06
GCST008526_75	Coffee consumption	9.000000e-06
GCST010276_6	Renal underexcretion gout	6.000000e-07
GCST010320_120	PR interval	9.000000e-14
GCST010321_185	PR interval	9.000000e-13
GCST010725_52	Malaria	4.000000e-07
GCST010796_2856	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_2857	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_2858	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST90006987_5	Gut microbiota relative abundance (Bifidobacterium)	7.000000e-06
GCST90093090_1	DHEAS levels	5.000000e-06
GCST90093091_3	DHEAS levels	3.000000e-06

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005109	energy expenditure
EFO:0005536	nitric oxide exhalation measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0004314	forced expiratory volume
EFO:0006781	coffee consumption measurement
EFO:0004462	PR interval
EFO:0004327	electrocardiography
EFO:0007874	gut microbiome measurement
EFO:0007001	dehydroepiandrosterone sulphate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2321643 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2485914	SMYD3		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 2.1.1.43 Histone methyltransferases (HMTs)

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

Ligand	Action	Affinity	Parameter
EPZ031686	Inhibition	8.52	pIC50
BAY-6035	Inhibition	7.06	pIC50
EM127	Inhibition	5.21	pKi

Binding affinities (BindingDB)

378 measured of 713 human assays (713 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-((1R,3R,5S)-8-(((1r,4R)-4-aminocyclohexyl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoindoline-5-carboxamide	IC50	0.44 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((1R,3r,5S)-8-((4-aminopiperidin-1-yl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-6-fluoro-2-oxoindoline-5-carboxamide	IC50	0.49 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((1R,3r,5S)-8-(((1-methylpiperidin-4-yl)methyl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoindoline-5-carboxamide	IC50	0.67 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((1R,3r,5S)-8-((4-aminopiperidin-1-yl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoindoline-5-carboxamide	IC50	0.68 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((1R,3r,5S)-8-((4-aminopiperidin-1-yl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-6-chloro-2-oxoindoline-5-carboxamide	IC50	0.81 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((2S,4S)-1-((4-aminopiperidin-1-yl)sulfonyl)-2-methylpiperidin-4-yl)-2-oxoindoline-5-carboxamide	IC50	0.9 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((1R,3r,5S)-8-(((1-(3-hydroxypropyl)piperidin-4-yl)methyl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoindoline-5-carboxamide	IC50	0.95 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((2S,4S)-1-((4-aminopiperidin-1-yl)sulfonyl)-2-methylpiperidin-4-yl)-6-chloro-2-oxoindoline-5-carboxamide	IC50	0.98 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((1R,3R,5S)-8-(((1r,4R)-4-aminocyclohexyl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-6-chloro-2-oxoindoline-5-carboxamide	IC50	1.1 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((2S)-1-((4-(2-aminopropan-2-yl)phenyl)sulfonyl)-2-methylpiperidin-4-yl)-2-oxoindoline-5-carboxamide	IC50	1.47 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
6-chloro-N-((1R,3r,5S)-8-(((1-(3-hydroxypropyl)piperidin-4-yl)methyl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoindoline-5-carboxamide	IC50	1.73 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
6-chloro-N-((1R,3r,5S)-8-((4-(methylamino)piperidin-1-yl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoindoline-5-carboxamide	IC50	1.89 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((1R,3r,5S)-8-((4-(benzylamino)piperidin-1-yl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoindoline-5-carboxamide	IC50	1.98 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((2S,4S)-1-((4-(2-aminopropan-2-yl)phenyl)sulfonyl)-2-methylpiperidin-4-yl)-6-chloro-2-oxoindoline-5-carboxamide	IC50	1.98 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((1R,3r,5S)-8-((4-(methylamino)piperidin-1-yl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoindoline-5-carboxamide	IC50	2.13 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
2-oxo-N-((1R,3r,5S)-8-((piperidin-3-ylmethyl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)indoline-5-carboxamide	IC50	2.14 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((1R,3R,5S)-8-(((1s,4S)-4-aminocyclohexyl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoindoline-5-carboxamide	IC50	2.33 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((1R,3r,5S)-8-((4-(benzylamino)piperidin-1-yl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-6-chloro-2-oxoindoline-5-carboxamide	IC50	2.58 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-((1R,3r,5S)-8-((4-(dimethylamino)piperidin-1-yl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoindoline-5-carboxamide	IC50	2.89 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
6-chloro-N-((1R,3r,5S)-8-((4-(dimethylamino)piperidin-1-yl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoindoline-5-carboxamide	IC50	3.46 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
6-chloro-2-oxo-N-((1R,3r,5S)-8-(((1-(4,4,4-trifluorobutyl)piperidin-4-yl)methyl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)indoline-5-carboxamide	IC50	3.54 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
6-chloro-2-oxo-N-((1R,3r,5S)-8-((piperidin-4-ylmethyl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)indoline-5-carboxamide	IC50	3.6 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
2-oxo-N-[(1R,5S)-8-(piperidin-4-ylmethylsulfonyl)-8-azabicyclo[3.2.1]octan-3-yl]-1,3-dihydroindole-5-carboxamide	IC50	3.98 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
6-chloro-2-oxo-N-[(1S,5R)-8-(piperidin-3-ylmethylsulfonyl)-8-azabicyclo[3.2.1]octan-3-yl]-1,3-dihydroindole-5-carboxamide	IC50	4.12 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(2S,4S)-2-methyl-1-(piperidin-4-ylmethylsulfonyl)piperidin-4-yl]-2-oxo-1,3-dihydroindole-5-carboxamide	IC50	4.42 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
2-oxo-N-[(1S,5R)-8-(piperidin-4-ylmethylsulfonyl)-8-azabicyclo[3.2.1]octan-3-yl]-3H-1,3-benzoxazole-6-carboxamide	IC50	5.21 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(1S,5R)-8-(4-aminopiperidin-1-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-6-bromo-2-oxo-1,3-dihydroindole-5-carboxamide	IC50	7.12 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(3S)-1-(4-aminopiperidin-1-yl)sulfonyl-3-methylpiperidin-4-yl]-6-chloro-2-oxo-1,3-dihydroindole-5-carboxamide	IC50	8.53 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(1S,5R)-8-(4-aminopiperidin-1-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-6-chloro-1-methyl-2-oxo-3H-indole-5-carboxamide	IC50	13.5 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(2S,4S)-1-(4-aminopiperidin-1-yl)sulfonyl-2-methylpiperidin-4-yl]-5-ethyl-1,2-thiazole-3-carboxamide	IC50	15.4 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(1S,5R)-8-(4-aminopiperidin-1-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-6-methyl-2-oxo-1,3-dihydroindole-5-carboxamide	IC50	15.6 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(2S,4S)-1-(4-aminopiperidin-1-yl)sulfonyl-2-methylpiperidin-4-yl]-5-cyclopropyl-1,3,4-thiadiazole-2-carboxamide	IC50	18.1 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(1R,5S)-8-(4-aminopiperidin-1-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-3-cyclopropyl-1,2-oxazole-5-carboxamide	IC50	18.5 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(3R,4R)-1-(4-aminopiperidin-1-yl)sulfonyl-3-methylpiperidin-4-yl]-6-chloro-2-oxo-1,3-dihydroindole-5-carboxamide	IC50	21.4 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(1S,5R)-8-(4-aminopiperidin-1-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-3-oxo-4H-1,4-benzoxazine-6-carboxamide	IC50	23.7 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(1S,5R)-8-(4-aminopiperidin-1-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-5-ethyl-1,2-thiazole-3-carboxamide	IC50	23.8 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
1-methyl-2-oxo-N-[(1R,5S)-8-(piperidin-4-ylmethylsulfonyl)-8-azabicyclo[3.2.1]octan-3-yl]-3H-indole-5-carboxamide	IC50	25.9 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(1S,2R,4S)-4-[[(3R)-3-aminobutanoyl]amino]-2-benzylcyclohexyl]-5-cyclopropyl-1,2-oxazole-3-carboxamide	IC50	28.6 nM	US-10106510: Substituted isoxazoles for treating cancer
N-[(1R,5S)-8-[4-(2-aminopropan-2-yl)phenyl]sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-2-oxo-1,3-dihydroindole-5-carboxamide	IC50	30.7 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(1S,5R)-8-[4-(2-aminopropan-2-yl)phenyl]sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-6-chloro-2-oxo-1,3-dihydroindole-5-carboxamide	IC50	37.1 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
6-chloro-2-oxo-N-[(1S,5R)-8-(2-pyrrolidin-1-ylethylsulfonyl)-8-azabicyclo[3.2.1]octan-3-yl]-1,3-dihydroindole-5-carboxamide	IC50	46 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
2-oxo-N-[(1R,5S)-8-(2-pyrrolidin-1-ylethylsulfonyl)-8-azabicyclo[3.2.1]octan-3-yl]-1,3-dihydroindole-5-carboxamide	IC50	49.7 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(1S,5R)-8-(4-aminopiperidin-1-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-5-ethylpyridazine-3-carboxamide	IC50	49.9 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
6-chloro-1-methyl-2-oxo-N-[(1S,5R)-8-(piperidin-4-ylmethylsulfonyl)-8-azabicyclo[3.2.1]octan-3-yl]-3H-indole-5-carboxamide	IC50	52.3 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(1R,5S)-8-(4-aminopiperidin-1-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-5-cyclopropyl-1,3,4-thiadiazole-2-carboxamide	IC50	55.8 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(2S,4S)-1-(4-aminopiperidin-1-yl)sulfonyl-2-methylpiperidin-4-yl]-5-ethylpyridazine-3-carboxamide	IC50	59.6 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
2-oxo-N-[1-(piperidin-4-ylmethylsulfonyl)piperidin-4-yl]-1,3-dihydroindole-5-carboxamide	IC50	68.2 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-(3-aminopropylsulfonyl)piperidin-4-yl]-6-chloro-2-oxo-1,3-dihydroindole-5-carboxamide	IC50	77.5 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[(1S,2R,4S)-4-[[(3R)-3-aminobutanoyl]amino]-2-ethylcyclohexyl]-5-ethyl-1,2-oxazole-3-carboxamide	IC50	97.3 nM	US-10106510: Substituted isoxazoles for treating cancer
N-((1r,4r)-4-(3-aminobutanamido)cyclohexyl)-2-oxoindoline-5-carboxamide	IC50	110 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer

ChEMBL bioactivities

1224 potent at pChembl≥5 of 1441 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.40	IC50	0.4	nM	CHEMBL5930708
9.36	IC50	0.44	nM	CHEMBL3799083
9.31	IC50	0.49	nM	CHEMBL3798134
9.22	IC50	0.6	nM	CHEMBL6062390
9.17	IC50	0.67	nM	CHEMBL3797708
9.17	IC50	0.68	nM	CHEMBL3798006
9.15	IC50	0.71	nM	CHEMBL5915469
9.12	IC50	0.76	nM	CHEMBL5817493
9.10	IC50	0.8	nM	CHEMBL5983928
9.10	IC50	0.8	nM	CHEMBL5749196
9.09	IC50	0.81	nM	CHEMBL3797749
9.06	IC50	0.88	nM	CHEMBL5976516
9.05	IC50	0.9	nM	CHEMBL6024972
9.05	IC50	0.9	nM	CHEMBL5767419
9.05	IC50	0.9	nM	CHEMBL5964919
9.05	IC50	0.9	nM	CHEMBL5956627
9.03	IC50	0.94	nM	CHEMBL5777063
9.02	IC50	0.95	nM	CHEMBL6012342
9.02	IC50	0.95	nM	CHEMBL5759159
9.01	IC50	0.98	nM	CHEMBL5969580
9.00	IC50	1	nM	CHEMBL3798006
9.00	IC50	1	nM	CHEMBL3797749
9.00	IC50	1	nM	CHEMBL3797708
9.00	IC50	1	nM	CHEMBL5880073
9.00	IC50	1	nM	CHEMBL5976948
8.99	IC50	1.03	nM	CHEMBL5989847
8.98	IC50	1.04	nM	CHEMBL6054359
8.97	IC50	1.07	nM	CHEMBL5910850
8.96	Ki	1.1	nM	CHEMBL3798741
8.96	IC50	1.1	nM	CHEMBL6052246
8.96	IC50	1.1	nM	CHEMBL6006815
8.95	IC50	1.12	nM	CHEMBL6195954
8.94	IC50	1.14	nM	CHEMBL6040217
8.93	IC50	1.18	nM	CHEMBL5874030
8.92	Ki	1.2	nM	CHEMBL3798741
8.92	IC50	1.2	nM	CHEMBL5920563
8.92	IC50	1.2	nM	CHEMBL5847089
8.92	IC50	1.2	nM	CHEMBL5984539
8.92	IC50	1.21	nM	CHEMBL5843540
8.91	IC50	1.22	nM	CHEMBL6020373
8.91	IC50	1.23	nM	CHEMBL5777827
8.91	IC50	1.24	nM	CHEMBL5845495
8.89	Ki	1.3	nM	CHEMBL3798468
8.89	IC50	1.3	nM	CHEMBL4594207
8.89	IC50	1.3	nM	CHEMBL5887443
8.89	IC50	1.3	nM	CHEMBL5894057
8.89	IC50	1.3	nM	CHEMBL5678791
8.89	IC50	1.3	nM	CHEMBL5917319
8.89	IC50	1.29	nM	CHEMBL5966075
8.87	IC50	1.36	nM	CHEMBL5930979

PubChem BioAssay actives

200 with measured affinity, of 418 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
N-[(1R,5S)-8-(4-aminopiperidin-1-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-2-oxo-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0010	uM
N-[(1S,5R)-8-(4-aminopiperidin-1-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-6-chloro-2-oxo-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0010	uM
N-[(1R,5S)-8-[(1-methylpiperidin-4-yl)methylsulfonyl]-8-azabicyclo[3.2.1]octan-3-yl]-2-oxo-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0010	uM
5-cyclopropyl-N-[1-[[4-[methyl(4,4,4-trifluorobutyl)amino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0010	uM
5-cyclopropyl-N-[1-[[4-(dimethylamino)cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0010	uM
5-cyclopropyl-N-[1-[[4-[(5-fluoro-2-pyridinyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0010	uM
N-[1-[[4-(benzylamino)cyclohexyl]methylsulfonyl]piperidin-4-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0010	uM
5-cyclopropyl-N-[1-[[4-[(3-fluorophenyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0010	uM
5-cyclopropyl-N-[1-[[4-[(2-methylphenyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0010	uM
N-[1-[[4-[(5-chloro-2-pyridinyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0010	uM
5-cyclopropyl-N-[1-[[4-[(5-fluoro-3-pyridinyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0010	uM
N-[1-[[4-[(4-chlorophenyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0010	uM
5-cyclopropyl-N-[1-[[4-(3,3,3-trifluoropropylamino)cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0010	uM
6-chloro-2-oxo-N-[(1S,5R)-8-[[1-(4,4,4-trifluorobutyl)piperidin-4-yl]methylsulfonyl]-8-azabicyclo[3.2.1]octan-3-yl]-1,3-dihydroindole-5-carboxamide	1296661: Non-competitive inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using varying N-terminal GST-tagged MEKK2 substrate and fixed SAM levels preincubated for 30 mins followed by substrate addition by filter plate assay	ki	0.0011	uM
N-[(1S,5R)-8-[4-(benzylamino)piperidin-1-yl]sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-6-chloro-2-oxo-1,3-dihydroindole-5-carboxamide	1296661: Non-competitive inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using varying N-terminal GST-tagged MEKK2 substrate and fixed SAM levels preincubated for 30 mins followed by substrate addition by filter plate assay	ki	0.0013	uM
5-cyclopropyl-N-[1-[[4-[(4-fluorophenyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0013	uM
N-[1-(4-aminocyclohexyl)sulfonylpiperidin-4-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0016	uM
N-[(1S,5R)-8-(4-aminocyclohexyl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide	2163211: Inhibition of SMYD3 (unknown origin) N-terminal GST-tagged MAP3K2 and 3H-SAM as substrate for 2 hrs by TopCount NXT plate reader	ic50	0.0018	uM
6-chloro-N-[(1S,5R)-8-[4-(methylamino)piperidin-1-yl]sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-2-oxo-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0020	uM
6-chloro-N-[(1S,5R)-8-[[1-(3-hydroxypropyl)piperidin-4-yl]methylsulfonyl]-8-azabicyclo[3.2.1]octan-3-yl]-2-oxo-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0020	uM
5-cyclopropyl-N-[1-[[4-[(2-fluorophenyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0025	uM
N-[1-[(4-aminocyclohexyl)methylsulfonyl]piperidin-4-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0025	uM
6-chloro-N-[(1S,5R)-8-[4-(dimethylamino)piperidin-1-yl]sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-2-oxo-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0030	uM
5-cyclopropyl-N-[1-[[4-(4,4,4-trifluorobutylamino)cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0032	uM
N-[(1R,5S)-8-(4-aminocyclohexyl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-2-oxo-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0040	uM
2-oxo-N-[(1R,5S)-8-(piperidin-4-ylmethylsulfonyl)-8-azabicyclo[3.2.1]octan-3-yl]-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0040	uM
6-chloro-2-oxo-N-[(1S,5R)-8-(piperidin-4-ylmethylsulfonyl)-8-azabicyclo[3.2.1]octan-3-yl]-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0040	uM
6-chloro-2-oxo-N-[(1S,5R)-8-[[(3S)-piperidin-3-yl]methylsulfonyl]-8-azabicyclo[3.2.1]octan-3-yl]-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0040	uM
N-[(1S,5R)-8-(4-aminopiperidin-1-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-6-fluoro-2-oxo-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0050	uM
6-chloro-2-oxo-N-[(1S,5R)-8-[[(3R)-piperidin-3-yl]methylsulfonyl]-8-azabicyclo[3.2.1]octan-3-yl]-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0050	uM
5-cyclopropyl-N-[1-[[4-[(5-methyl-2-pyridinyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0050	uM
5-cyclopropyl-N-[1-[[4-(methylamino)cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0050	uM
5-cyclopropyl-N-[1-[4-(4,4,4-trifluorobutylamino)cyclohexyl]sulfonylpiperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0063	uM
N-[1-[[4-[(3-chlorophenyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0080	uM
5-cyclopropyl-N-[1-[[4-[(4-fluoro-2-pyridinyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0100	uM
5-cyclopropyl-N-[1-[[4-[(3-methylphenyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0100	uM
propyl (2R)-4-[2-[4-(1-aminocyclopropyl)phenyl]-4-chloroquinoline-7-carbonyl]-2-methylpiperazine-1-carboxylate	1510670: Inhibition of SMYD3 (unknown origin) using MAP3K2 peptide as substrate pretreated for 30 mins followed by substrate addition and measured after 30 mins by MTase Glo reagent based luminescence assay	ic50	0.0117	uM
N-[(1S,5R)-8-(4-aminopiperidin-1-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]-6-methyl-2-oxo-1,3-dihydroindole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0160	uM
5-cyclopropyl-N-[1-[4-(pyrrolidin-1-ylmethyl)phenyl]sulfonylpiperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0160	uM
5-cyclopropyl-N-[1-[[4-(2-methylpropylamino)cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0160	uM
5-cyclopropyl-N-(1-piperidin-4-ylsulfonylpiperidin-4-yl)-1,2-oxazole-3-carboxamide	1541953: Uncompetitive inhibition of SMYD3 (unknown origin) assessed as inhibitory constant incubated for 60 mins by Cheng-Prusoff equation analysis	ki	0.0170	uM
N-[1-[4-(azetidin-1-ylmethyl)phenyl]sulfonylpiperidin-4-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0200	uM
5-cyclopropyl-N-[1-[[4-[(4-methylphenyl)methylamino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0200	uM
5-cyclopropyl-N-[1-[[4-[ethyl(4,4,4-trifluorobutyl)amino]cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0200	uM
5-cyclopropyl-N-[1-[[4-(3,3-dimethylbutylamino)cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0200	uM
(2S)-1-(4-aminopiperidine-1-carbonyl)-N-(2-cyclopropylethyl)-2-methyl-4-oxo-3,5-dihydro-2H-1,5-benzodiazepine-7-carboxamide	2162032: Binding affinity to recombinant human SMYD3 expressed in Escherichia coli assessed as catalytic inhibition using DYDNPIFEKFGKGGTYPRRYHVSYHGK-Biotin as substrate by scintillation proximity assay	ic50	0.0245	uM
5-cyclopropyl-N-[1-[[4-(pyridin-2-ylmethylamino)cyclohexyl]methylsulfonyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0250	uM
N-[1-(4-aminobutylsulfonyl)piperidin-4-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0250	uM
N-[1-[4-(aminomethyl)cyclohexyl]sulfonylpiperidin-4-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide	1541949: Inhibition of recombinant N-terminal FLAG/His-tagged SMYD3 (unknown origin) expressed in baculovirus infected insect cells using 3H-SAM as substrate assessed as 3H-MEKK2 methylation incubated for 40 mins by scintillation proximity assay	ic50	0.0250	uM
1-methyl-2-oxo-N-[(1R,5S)-8-(piperidin-4-ylmethylsulfonyl)-8-azabicyclo[3.2.1]octan-3-yl]-3H-indole-5-carboxamide	1296641: Inhibition of full length N-terminal His-tagged SMYD3 (1 to 428 residues) (unknown origin) expressed in Escherichia coli using N-terminal GST-tagged MEKK2 as substrate preincubated for 30 mins followed by substrate addition by scintillation proximity assay in presence of [3H]SAM	ic50	0.0260	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	10
Aflatoxin B1	affects expression, decreases expression, increases methylation	7
Cisplatin	affects expression, affects cotreatment, decreases expression	4
Valproic Acid	affects expression, increases expression, increases methylation	4
bisphenol A	increases methylation, decreases expression	2
sodium arsenite	increases abundance, increases expression, affects methylation	2
Arsenic	affects methylation, increases abundance, increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Methyl Methanesulfonate	decreases expression	2
Progesterone	increases expression, affects cotreatment	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
cobaltous chloride	decreases expression	1
nickel sulfate	decreases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
beta-methylcholine	affects expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
K 7174	decreases expression	1
ICG 001	affects expression	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
incobotulinumtoxinA	increases expression	1

ChEMBL screening assays

129 unique, capped per target: 127 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2330196	Binding	Inhibition of SMYD3 (unknown origin) using histone H3-H4 tetramer as substrate after 1 hr by filter plate assay in presence of [3H]-S-adenosylmethionine	Exploiting an allosteric binding site of PRMT3 yields potent and selective inhibitors. — J Med Chem
CHEMBL5723138	Functional	Affinity Biochemical interaction: (inhibition of methylation activity, scintillation proximity assay utilizing [3 H]-SAM with specific product capture of biotin-tagged peptides on streptavidin SPA beads) EUB0002243aAD SMYD3	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7ZI	Abcam Raji SMYD3 KO	Cancer cell line	Male
CVCL_C0AB	Abcam THP-1 SMYD3 KO	Cancer cell line	Male
CVCL_C7BZ	Abcam PC-3 SMYD3 KO	Cancer cell line	Male
CVCL_TP74	HAP1 SMYD3 (-) 1	Cancer cell line	Male
CVCL_XT59	HAP1 SMYD3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03799705	Not specified	COMPLETED	Genetic Variants in Nicotinamide Adenine Dinucleotide (NAD) Synthesis Pathway