SMYD2

Summary

SMYD2 (SET and MYND domain containing 2, HGNC:20982) is a protein-coding gene on chromosome 1q32.3, encoding N-lysine methyltransferase SMYD2 (Q9NRG4). Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1.

SET domain-containing proteins, such as SMYD2, catalyze lysine methylation (Brown et al., 2006 [PubMed 16805913]).

Source: NCBI Gene 56950 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 71 total
• Druggable target: yes
• MANE Select transcript: NM_020197

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20982
Approved symbol	SMYD2
Name	SET and MYND domain containing 2
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Aliases	HSKM-B, ZMYND14, KMT3C
Ensembl gene	ENSG00000143499
Ensembl biotype	protein_coding
OMIM	610663
Entrez	56950

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000366957, ENST00000416415, ENST00000460580, ENST00000471645, ENST00000484459, ENST00000491455, ENST00000873620, ENST00000927350, ENST00000950473, ENST00000950474, ENST00000950475, ENST00000950476, ENST00000950477, ENST00000950478, ENST00000950479, ENST00000950480, ENST00000950481

RefSeq mRNA: 1 — MANE Select: NM_020197 NM_020197

CCDS: CCDS31022

Canonical transcript exons

ENST00000366957 — 12 exons

Exon	Start	End
ENSE00001938471	214281159	214281427
ENSE00003471373	214324641	214324708
ENSE00003475226	214334200	214334308
ENSE00003485334	214330950	214331070
ENSE00003498339	214336704	214337131
ENSE00003508888	214327622	214327724
ENSE00003556280	214330168	214330278
ENSE00003557401	214314762	214314872
ENSE00003560282	214318859	214318983
ENSE00003611894	214318079	214318139
ENSE00003662057	214332018	214332192
ENSE00003670265	214305187	214305250

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.1756 / max 257.0816, expressed in 1795 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8532	11.4566	1778
8533	1.1182	703
8529	0.9249	575
8531	0.7688	488
201949	0.5010	273
8530	0.3355	144
8528	0.0706	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.53	gold quality
heart right ventricle	UBERON:0002080	98.83	gold quality
apex of heart	UBERON:0002098	98.41	gold quality
cardiac ventricle	UBERON:0002082	98.40	gold quality
heart left ventricle	UBERON:0002084	98.39	gold quality
epithelium of bronchus	UBERON:0002031	97.80	gold quality
bronchial epithelial cell	CL:0002328	97.77	gold quality
bronchus	UBERON:0002185	97.60	gold quality
vastus lateralis	UBERON:0001379	96.68	gold quality
gluteal muscle	UBERON:0002000	96.47	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.43	gold quality
diaphragm	UBERON:0001103	96.37	gold quality
quadriceps femoris	UBERON:0001377	96.25	gold quality
skeletal muscle tissue	UBERON:0001134	95.61	gold quality
muscle organ	UBERON:0001630	95.46	gold quality
deltoid	UBERON:0001476	95.45	gold quality
gastrocnemius	UBERON:0001388	95.41	gold quality
muscle of leg	UBERON:0001383	95.28	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.20	gold quality
tongue squamous epithelium	UBERON:0006919	95.20	gold quality
biceps brachii	UBERON:0001507	95.13	gold quality
triceps brachii	UBERON:0001509	95.06	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.01	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.68	gold quality
orbitofrontal cortex	UBERON:0004167	94.45	gold quality
postcentral gyrus	UBERON:0002581	94.43	gold quality
superior frontal gyrus	UBERON:0002661	94.40	gold quality
muscle tissue	UBERON:0002385	94.38	gold quality
middle temporal gyrus	UBERON:0002771	94.34	gold quality
parietal lobe	UBERON:0001872	94.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPG

miRNA regulators (miRDB)

46 targeting SMYD2, 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-3646	100.00	73.56	5283
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-519A-3P	99.67	71.67	1868

Literature-anchored findings (GeneRIF, showing 40)

• The combination of the SMYD2 interactome with the gene expression data suggests that some of the genes regulated by SMYD2 are closely associated with SMYD2-interacting proteins. (PMID:18065756)
• SMYD2 plays an important role in tumor cell proliferation through its activation/overexpression and highlight its usefulness as a prognosticator and potential therapeutic target in ESCC. (PMID:19423649)
• RB monomethylation at lysine 860 by SMYD2 provides a direct binding site for L3MBTL1. (PMID:20870719)
• SMYD2 gene expression is decreased in both classic and follicular variants of papillary thyroid carcinoma. (PMID:21509594)
• Substrate specificity and product analysis studies established SMYD2 as a monomethyltransferase that prefers nonmethylated p53 peptide substrate. (PMID:21678921)
• Data report the crystal structure of the full-length human Smyd2 in complex with S-adenosyl-L-homocysteine (AdoHcy). (PMID:21724641)
• Structural basis of substrate methylation and inhibition of SMYD2 (PMID:21782458)
• SMYD2 has a role in specifically recognizing and regulating functions of p53 tumor suppressor through Lys-370 monomethylation (PMID:21880715)
• Data highlights the ability of SMYD proteins to form unique protein complexes that may underlie their various biological functions and the SMYD2-mediated methylation of the key molecular chaperone HSP90. (PMID:22028380)
• -dependent RB1 methylation at lysine 810 promotes cell cycle progression of cancer cells. Further study may explore SMYD2-dependent RB1 methylation as a potential therapeutic target in human cancer. (PMID:22787429)
• Findings suggest that SMYD2 (SET and MYND domain containing protein 2), a histone lysine methyltransferase, in embryonic stem (ES) cell differentiation. (PMID:23873367)
• Data suggest that SMYD2-mediated estrogen receptor alpha (ERalpha) protein methylation and p300/cAMP response element-binding protein-binding protein-dependent ERalpha acetylation play an important role in the estrogen-induced gene expression profiles. (PMID:24101509)
• Data indicate that irect estrogen receptor alpha (ERalpha) methylation by histone methyltransferase SMYD2 regulates estrogen signaling. (PMID:24594358)
• SMYD2 expression is altered in acute lymphoblastic leukemia bone marrow samples and its high expression was correlated with a bad prognosis. Moreover, SMYD2 expression level significantly decreases in patients that respond to chemotherapy treatment. (PMID:24631370)
• a novel mechanism of PARP1 in human cancer through its methylation by SMYD2 (PMID:24726141)
• A novel mechanism for human carcinogenesis via methylation of HSP90AB1 by SMYD2. (PMID:24880080)
• SMYD2 has a crucial role in tumor cell proliferation by its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in gastric cancer. (PMID:25321194)
• Comprehensive motif-based searches and mutational analysis further established four additional substrates of SMYD2. (PMID:25533488)
• in addition to esophageal squamous cell carcinoma, SMYD2 is also amplified and/or overexpressed in breast and liver primary tumors (PMID:25825497)
• SMYD2-mediated methylation negatively regulates PTEN tumor suppressor activity and results in activation of the phosphatidylinositol 3-kinase-AKT pathway. (PMID:25925379)
• Results show that high expression levels of SMYD2, SETD3, and NO66 in renal cell tumors. Their low expression levels were significantly associated with shorter disease-specific and disease-free survival. (PMID:26488939)
• Study reveals a collection of 10 enriched sequence motifs in Kme1 sites that were identified upon SMYD2 overexpression which were also downregulated in response to SMYD2 knockdown. These findings suggest that these motifs reflect the substrate specificity of SMYD2 in esophageal squamous cell carcinoma cell line. (PMID:26750096)
• High expression of SMYD2 is associated with chronic lymphocytic leukemia. (PMID:26790435)
• Suggest that SMYD2 plays a role in tumor progression and might be a useful prognosticator in HPV-unrelated, nonmultiple head and neck squamous cell carcinomas. (PMID:26826421)
• identifie novel cellular substrates of the lysine methyltransferase SMYD2. Of the 14 novel putative SMYD2 substrates identified, six were confirmed in cells by immunoprecipitation: MAPT, CCAR2, EEF2, NCOA3, STUB1, and UTP14A. Treatment with the selective SMYD2 inhibitor BAY-598 abrogated the methylation signal, indicating that methylation of these novel substrates was dependent on the catalytic activity of SMYD2 (PMID:27163177)
• Lysine methylation represses p53 activity in teratocarcinoma cancer cells via up-regulation of SMYD2 and PR-Set7 and perpetuation of cancer cells proliferation. (PMID:27535933)
• Substrate crevices of Smyd2 and Smyd3 show distinct features in terms of spatial, hydration, and electrostatic properties that emphasize their characteristic modes of substrates interaction and entry pathways for inhibitor binding. (PMID:27959541)
• SMYD2 knockdown confers relative resistance to human AML cells against multiple classes of DNA damaging agents. (PMID:28187429)
• Knockdown of SMYD2 as well as treatment with a SMYD2 inhibitor in two NSCLC cell lines with an EML4-ALK gene significantly attenuated the phosphorylation levels of the EML4-ALK protein. (PMID:28370702)
• SMYD2-H4K20me1-L3MBTL1 axis contributes to HIV-1 latency and can be targeted with small-molecule SMYD2 inhibitors. (PMID:28494238)
• The SMYD2 may promote BMP signaling by directly methylating BMPR2, which, in turn, stimulates BMPR2 kinase activity and activation of the BMP pathway. (PMID:28588028)
• The expression of SMYD2 can be upregulated by IL-6-STAT3 and TNFalpha-NF-kappaB signaling, which integrates epigenetic regulation to inflammation in triple-negative breast cancer development. (PMID:29487338)
• Study shows a significant association between the methylation status of CpGs in the SMYD2 promoter and SMYD2 gene decreased expression in abdominal aortic aneurysm. (PMID:29507647)
• We show that tool compounds as well as CRISPR/Cas9 fail to reproduce many of the cell proliferation findings associated with SMYD2 and SMYD3 inhibition previously obtained with RNAi based approaches and with early stage chemical probes. (PMID:29856759)
• the observed complex formation between SMYD2 and HSP90/P23 may contribute to ERalpha regulation. (PMID:30190324)
• Germline SMYD2 alleles are associated with bad clinical outcome of first-line platinum-based treatment in advanced Non-Small-Cell-Lung-Cancer patients and might be used as prognostic signature directing patient stratification and the choice of therapy. (PMID:30207284)
• We found that SMYD2 expression was significantly related to tumor size (P<0.001), lymph node metastasis (P<0.005), and TNM stage (P<0.005). However, no correlations were found between SMYD2 expression and patient age, sex, thyroid capsular invasion (TCI), or extrathyroidal extension (all P>0.05). (PMID:30319138)
• Results reveal that the histone methyltransferase SMYD2 is dispensable in the undifferentiated hESCs and the early neuroectodermal differentiation, but it promotes the mesendodermal differentiation of hESCs through the epigenetic control of critical genes to mesendodermal lineage commitment. (PMID:31348575)
• The recent surge of data on SMYD2 structure and function highlights that SMYD2 is a critical regulator of cardiovascular disease and cancer. Most studies have demonstrated that SMYD2 methylates nonhistone proteins to achieve its function, which is consistent with the fact that SMYD2 primarily localizes to the cytoplasm. [review] (PMID:31370883)
• Analysis of the Substrate Specificity of the SMYD2 Protein Lysine Methyltransferase and Discovery of Novel Non-Histone Substrates. (PMID:31612581)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	smyd2a	ENSDARG00000055151
mus_musculus	Smyd2	ENSMUSG00000026603
rattus_norvegicus	Smyd2	ENSRNOG00000003583
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), SMYD3 (ENSG00000185420), SMYD4 (ENSG00000186532)

Protein

Protein identifiers

N-lysine methyltransferase SMYD2 — Q9NRG4 (reviewed: Q9NRG4)

Alternative names: HSKM-B, Histone methyltransferase SMYD2, Lysine N-methyltransferase 3C, SET and MYND domain-containing protein 2

All UniProt accessions (2): Q9NRG4, B0R0U3

UniProt curated annotations — full annotation on UniProt →

Function. Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically trimethylates histone H3 ‘Lys-4’ (H3K4me3) in vivo. The activity requires interaction with HSP90alpha. Shows even higher methyltransferase activity on p53/TP53. Monomethylates ‘Lys-370’ of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates RB1 at ‘Lys-860’.

Subunit / interactions. Interacts with RNA polymerase II and HELZ. Interacts with SIN3A and HDAC1. Interacts (via MYND-type zinc finger) with EPB41L3. Interacts (via SET domain) with p53/TP53. Interacts with RB1 and HSP90AA1.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Induction. Expression is repressed by CEBPA.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRG4-1	1	yes
Q9NRG4-2	2

RefSeq proteins (1): NP_064582* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR002893	Znf_MYND	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR044419	SMYD2_SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR050869	H3K4_H4K5_MeTrfase	Family

Pfam: PF00856, PF01753

Catalyzed reactions (Rhea), 2 shown:

• L-lysyl-[protein] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine + H(+) (RHEA:51736)
• 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 (74 total): helix 22, strand 13, binding site 12, mutagenesis site 12, turn 8, sequence variant 2, chain 1, domain 1, modified residue 1, splice variant 1, zinc finger region 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
4WUY	X-RAY DIFFRACTION	1.63
5ARF	X-RAY DIFFRACTION	1.92
5KJK	X-RAY DIFFRACTION	1.93
6CBX	X-RAY DIFFRACTION	1.94
5ARG	X-RAY DIFFRACTION	1.99
3TG4	X-RAY DIFFRACTION	2
5WCG	X-RAY DIFFRACTION	2.02
9CKC	X-RAY DIFFRACTION	2.1
5KJM	X-RAY DIFFRACTION	2.19
3S7D	X-RAY DIFFRACTION	2.3
3TG5	X-RAY DIFFRACTION	2.3
3S7B	X-RAY DIFFRACTION	2.42
6N3G	X-RAY DIFFRACTION	2.43
9CKF	X-RAY DIFFRACTION	2.5
6CBY	X-RAY DIFFRACTION	2.55
5V3H	X-RAY DIFFRACTION	2.69
5KJL	X-RAY DIFFRACTION	2.7
6MON	X-RAY DIFFRACTION	2.71
5KJN	X-RAY DIFFRACTION	2.72
9CKG	X-RAY DIFFRACTION	2.75
3RIB	X-RAY DIFFRACTION	2.79
4YND	X-RAY DIFFRACTION	2.79
4O6F	X-RAY DIFFRACTION	2.82
3S7F	X-RAY DIFFRACTION	2.85
3S7J	X-RAY DIFFRACTION	3.04

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRG4-F1	97.40	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 (12): 86; 90; 137; 206–207; 258–260; 17–19; 52; 55; 65; 68; 74; 78

Post-translational modifications (1): 283

Mutagenesis-validated functional residues (12):

Position	Phenotype
187	abolishes methyltransferase activity on p53/tp53.
189	strongly reduces methyltransferase activity on p53/tp53.
190	strongly reduces methyltransferase activity on p53/tp53.
207	abolishes methyltransferase activity.
240	abolishes methyltransferase activity.
245	strongly reduces methyltransferase activity on p53/tp53.
252	slightly reduces methyltransferase activity on p53/tp53.
253	no effect on methyltransferase activity on p53/tp53.
306	no effect on methyltransferase activity on p53/tp53.
374	abolishes methyltransferase activity on p53/tp53.
429	reduces methyltransferase activity on p53/tp53.
431	strongly reduces methyltransferase activity on p53/tp53.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-6804760	Regulation of TP53 Activity through Methylation
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-4839726	Chromatin organization
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 204 (showing top): CREL_01, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_DNA_DAMAGE_RESPONSE_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_PEPTIDYL_LYSINE_MODIFICATION, MORF_ZNF10, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, GOBP_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, MORF_EPHA7, MORF_RAB3A, MORF_BMPR2, LYF1_01, AACTTT_UNKNOWN, CAIRO_HEPATOBLASTOMA_UP

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), heart development (GO:0007507), negative regulation of cell population proliferation (GO:0008285), peptidyl-lysine monomethylation (GO:0018026), peptidyl-lysine dimethylation (GO:0018027), regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043516), regulation of signal transduction by p53 class mediator (GO:1901796), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), methylation (GO:0032259)

GO Molecular Function (13): RNA polymerase II complex binding (GO:0000993), p53 binding (GO:0002039), zinc ion binding (GO:0008270), lysine N-methyltransferase activity (GO:0016278), protein-lysine N-methyltransferase activity (GO:0016279), histone H3K36 methyltransferase activity (GO:0046975), histone H3 methyltransferase activity (GO:0140938), 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), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Regulation of TP53 Activity	1
RNA Polymerase II Transcription	1
Chromatin organization	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
peptidyl-lysine methylation	2
protein methyltransferase activity	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
animal organ development	1
circulatory system development	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
DNA damage response, signal transduction by p53 class mediator	1
regulation of cellular response to stress	1
regulation of signal transduction by p53 class mediator	1
signal transduction by p53 class mediator	1
regulation of intracellular signal transduction	1
cellular component organization	1
chromatin organization	1
metabolic process	1
RNA polymerase core enzyme binding	1
protein binding	1
transition metal ion binding	1
N-methyltransferase activity	1
S-adenosylmethionine-dependent methyltransferase activity	1
lysine N-methyltransferase activity	1
protein-lysine N-methyltransferase activity	1
histone H3 methyltransferase activity	1
histone methyltransferase activity	1
histone H3K4 methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
histone modifying activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1823 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMYD2	SETD7	Q8WTS6	857
SMYD2	HSP90AA1	P07900	851
SMYD2	HSP90AB1	P08238	851
SMYD2	KMT5A	Q9NQR1	780
SMYD2	SETD3	Q86TU7	706
SMYD2	KDM1A	O60341	698
SMYD2	ASH1L	Q9NR48	679
SMYD2	SETD2	Q9BYW2	674
SMYD2	EHMT2	Q96KQ7	669
SMYD2	SUV39H2	Q9H5I1	641
SMYD2	DOT1L	Q8TEK3	639
SMYD2	EHMT1	Q9H9B1	629
SMYD2	TP53	P04637	628
SMYD2	SUV39H1	O43463	623
SMYD2	NSD2	O96028	620

IntAct

79 interactions, top by confidence:

A	B	Type	Score
TP53	SMYD2	psi-mi:“MI:0557”(adp ribosylation reaction)	0.810
TP53	SMYD2	psi-mi:“MI:0213”(methylation reaction)	0.810
SMYD2	TP53	psi-mi:“MI:0407”(direct interaction)	0.810
SMYD2	TP53	psi-mi:“MI:0213”(methylation reaction)	0.810
CILK1	SMYD2	psi-mi:“MI:0915”(physical association)	0.660
CPSF4	FIP1L1	psi-mi:“MI:0914”(association)	0.660
SMYD2	SNX11	psi-mi:“MI:0915”(physical association)	0.560
BTF3L4	SMYD2	psi-mi:“MI:0915”(physical association)	0.560
BTF3	SMYD2	psi-mi:“MI:0915”(physical association)	0.560
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.530
ZFC3H1	HNRNPCL1	psi-mi:“MI:0914”(association)	0.530
ZNF408	LRP4	psi-mi:“MI:0914”(association)	0.530
MPZL3	SMYD2	psi-mi:“MI:0915”(physical association)	0.400
CELA1	KRBA1	psi-mi:“MI:0914”(association)	0.350
TXNDC9	TUBAL3	psi-mi:“MI:0914”(association)	0.350
JPH4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
ZFC3H1	ANKHD1	psi-mi:“MI:0914”(association)	0.350
ZNF408		psi-mi:“MI:0914”(association)	0.350
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.350
CPSF4	P4HA2	psi-mi:“MI:0914”(association)	0.350
GOLGA4	TKT	psi-mi:“MI:0914”(association)	0.350
CCSER1	SMYD2	psi-mi:“MI:0914”(association)	0.350
SMYD2	HSPA4L	psi-mi:“MI:0914”(association)	0.350
CILK1	MAST4	psi-mi:“MI:0914”(association)	0.350
ZBTB3	VWA8	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350

BioGRID (88): SMYD2 (Affinity Capture-RNA), SMYD2 (Affinity Capture-RNA), ESR1 (Biochemical Activity), SMYD2 (Affinity Capture-MS), SMYD2 (Co-fractionation), SMYD2 (Affinity Capture-MS), SMYD2 (Affinity Capture-MS), SMYD2 (Affinity Capture-MS), SMYD2 (Affinity Capture-MS), SMYD2 (Affinity Capture-MS), SMYD2 (Affinity Capture-MS), SMYD2 (Affinity Capture-MS), SMYD2 (Affinity Capture-MS), SMYD2 (Affinity Capture-MS), SMYD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QP51, A2RU49, A5PJU6, A8WFT6, B4G0F3, B8BKI7, C3RZA1, C6JS30, E0CTF3, F4IVI0, F4KFT7, G1SPE9, O23617, O55060, P11172, P31754, P54319, Q0P585, Q3BCQ8, Q3BCR2, Q5IH13, Q5IH14, Q5R5S1, Q5U5V2, Q6EIC1, Q6GM82, Q6I581, Q6IQS6, Q6PB06, Q6YXW6, Q7M6Z3, Q7SY78, Q80SY6, Q8BGT5, Q8L5Z4, Q8L7M0, Q8R5A0, Q8TD30, Q8VZM1, Q90678

Diamond homologs: A3M0J3, A5DQN2, A6ZTB4, A7TPV3, E1C5V0, O74467, P38890, Q5A1M3, Q5RGL7, Q6BSV3, Q6C9E7, Q6CX91, Q6FTT0, Q6GN68, Q75BF1, Q9NRG4, A9CPT4, C3RZA1, D3ZKV9, F1QN74, F1RET2, P97443, Q0P585, Q12529, Q3TYX3, Q4VC12, Q5BJI7, Q5F3V0, Q5R5X9, Q5UNT8, Q5ZIZ2, Q6GMV2, Q6GPQ4, Q7M6Z3, Q7TSV3, Q7ZXV5, Q8BTK5, Q8IYR2, Q8NB12, Q8R5A0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EML4-ALK	“up-regulates activity”	SMYD2	methylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2741 predictions. Top by Δscore:

Variant	Effect	Δscore
1:214281425:CAGGT:C	donor_loss	1.0000
1:214281428:G:GA	donor_loss	1.0000
1:214314751:A:AG	acceptor_gain	1.0000
1:214314758:CCAG:C	acceptor_loss	1.0000
1:214314759:CAG:C	acceptor_loss	1.0000
1:214314760:A:AG	acceptor_gain	1.0000
1:214314760:AGAA:A	acceptor_loss	1.0000
1:214314761:G:GA	acceptor_loss	1.0000
1:214314761:G:GG	acceptor_gain	1.0000
1:214314869:ACAGG:A	donor_loss	1.0000
1:214314870:CAGG:C	donor_loss	1.0000
1:214314871:AGGT:A	donor_loss	1.0000
1:214314872:GGTG:G	donor_loss	1.0000
1:214314873:GTGAG:G	donor_loss	1.0000
1:214314874:T:A	donor_loss	1.0000
1:214318070:A:AG	acceptor_gain	1.0000
1:214324705:C:CG	donor_gain	1.0000
1:214324705:C:G	donor_gain	1.0000
1:214324707:GA:G	donor_gain	1.0000
1:214324709:G:GG	donor_gain	1.0000
1:214326572:G:GT	donor_gain	1.0000
1:214327612:T:TA	acceptor_gain	1.0000
1:214330163:CGTA:C	acceptor_loss	1.0000
1:214330165:TA:T	acceptor_loss	1.0000
1:214330166:A:AC	acceptor_loss	1.0000
1:214281410:C:T	donor_gain	0.9900
1:214314761:GAAA:G	acceptor_gain	0.9900
1:214318070:AATT:A	acceptor_gain	0.9900
1:214318071:A:G	acceptor_gain	0.9900
1:214318140:G:GG	donor_gain	0.9900

AlphaMissense

2889 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:214305206:T:C	C65R	1.000
1:214305215:T:C	C68R	1.000
1:214314847:T:C	L108P	1.000
1:214324656:T:C	F184L	1.000
1:214324657:T:C	F184S	1.000
1:214324658:C:A	F184L	1.000
1:214324658:C:G	F184L	1.000
1:214324678:T:C	L191P	1.000
1:214324689:G:A	G195R	1.000
1:214324689:G:C	G195R	1.000
1:214324690:G:A	G195E	1.000
1:214327640:T:A	H207Q	1.000
1:214327640:T:G	H207Q	1.000
1:214327644:T:C	C209R	1.000
1:214330177:A:C	S239R	1.000
1:214330179:C:A	S239R	1.000
1:214330179:C:G	S239R	1.000
1:214330211:G:C	R250T	1.000
1:214330211:G:T	R250I	1.000
1:214330212:A:C	R250S	1.000
1:214330212:A:T	R250S	1.000
1:214330223:T:C	L254S	1.000
1:214330240:T:C	F260L	1.000
1:214330242:T:A	F260L	1.000
1:214330242:T:G	F260L	1.000
1:214330246:T:C	C262R	1.000
1:214281408:T:C	C52R	0.999
1:214281409:G:A	C52Y	0.999
1:214281410:C:G	C52W	0.999
1:214305206:T:A	C65S	0.999

dbSNP variants (sampled 300 via entrez): RS1000010084 (1:214296387 T>C), RS1000029442 (1:214300694 A>T), RS1000034019 (1:214289040 A>G), RS1000290844 (1:214333496 C>T), RS1000332451 (1:214320303 C>G,T), RS1000340206 (1:214296730 T>C,G), RS1000345689 (1:214315320 G>A), RS1000419376 (1:214314997 T>C), RS1000484087 (1:214280816 G>A,C), RS1000484505 (1:214300939 T>C), RS1000497205 (1:214305046 T>C), RS1000526902 (1:214321684 G>A), RS1000598051 (1:214305902 A>G), RS1000614557 (1:214328696 T>C), RS1000697105 (1:214286218 G>A)

Disease associations

OMIM: gene MIM:610663 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003877_7	Abdominal aortic aneurysm	9.000000e-11
GCST006479_17	Diverticular disease	8.000000e-06
GCST012117_2	Rheumatic heart disease	1.000000e-06
GCST90000047_21	Age at first sexual intercourse	1.000000e-08
GCST90011900_30	Serum alkaline phosphatase levels	2.000000e-20

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease
EFO:0009749	age at first sexual intercourse measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2169716 (SINGLE PROTEIN)

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

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
LLY-507	Inhibition	7.82	pIC50
BAY-598	Inhibition	7.57	pIC50
AZ505	Inhibition	6.92	pIC50

Binding affinities (BindingDB)

353 measured of 384 human assays (384 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[1-[[1-[(4-chlorophenyl)methyl]pyrazol-4-yl]methyl]azetidin-3-yl]-5-cyclopropylpyridazine-3-carboxamide	IC50	1.2 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-[[1-[(4-chlorophenyl)methyl]pyrazol-4-yl]methyl]azetidin-3-yl]-4-cyclopropylpyridine-2-carboxamide	IC50	3.3 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-[[1-[(4-chlorophenyl)methyl]pyrazol-4-yl]methyl]azetidin-3-yl]-1-cyclopropyltriazole-4-carboxamide	IC50	3.9 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
Rac-N-[1-(N′-cyano-N-{5-(difluoromethoxy)-2-[3-(dimethylamino)propoxy]phenyl}-carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	IC50	5.55 nM	US-10023539: Aryl-cyanoguanidine compounds
N-[1-{N′-cyano-N-[2-methoxy-5-(trifluoromethyl)phenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide Isomer 1	IC50	6.65 nM	US-10023539: Aryl-cyanoguanidine compounds
N-[1-[(1-benzylpyrazol-4-yl)methyl]azetidin-3-yl]-5-cyclopropylpyridazine-3-carboxamide	IC50	7.8 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
Rac-N-[1-(N′-cyano-N-{2-[(1-methylpiperidin-4-yl)oxy]-5-(trifluoromethyl)phenyl}-carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	IC50	9.09 nM	US-10023539: Aryl-cyanoguanidine compounds
Rac-N-[1-{N′-cyano-N-[2-methoxy-5-(trifluoromethyl)phenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	IC50	9.98 nM	US-10023539: Aryl-cyanoguanidine compounds
N-[1-[[1-[(4-chlorophenyl)methyl]pyrazol-4-yl]methyl]azetidin-3-yl]-5-cyclopropyl-1H-imidazole-2-carboxamide	IC50	11 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
Rac-N-[1-{N′-cyano-N-[5-(difluoromethoxy)-2-methoxyphenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	IC50	12.5 nM	US-10023539: Aryl-cyanoguanidine compounds
(2R)—N-[1-{N′-cyano-N-[3-(difluoromethoxy)phenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxypropanamide (1:1 Mixture of Diastereomers)	IC50	13 nM	US-10023539: Aryl-cyanoguanidine compounds
N-[1-[(1-benzylpyrazol-4-yl)methyl]azetidin-3-yl]-4-cyclopropylpyridine-2-carboxamide	IC50	13 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
1-cyclopropyl-N-[1-[[1-[[4-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]methyl]azetidin-3-yl]triazole-4-carboxamide	IC50	14 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
Rac-N-[1-{N′-cyano-N-[3-(difluoromethoxy)phenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethylglycinamide	IC50	15 nM	US-10023539: Aryl-cyanoguanidine compounds
Rac-N-[r-(N′-cyano-N-[2-[2-(pyrrolidin-1-yl)ethoxy]-5-(trifluormethyl)phenyl]carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	IC50	15.8 nM	US-10023539: Aryl-cyanoguanidine compounds
1-cyclopropyl-N-[1-[[1-[(4-methylphenyl)methyl]pyrazol-4-yl]methyl]azetidin-3-yl]triazole-4-carboxamide	IC50	16 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-[(1-benzylpyrazol-4-yl)methyl]azetidin-3-yl]-1-cyclopropyltriazole-4-carboxamide	IC50	16.4 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-{N′-cyano-N-[3-(difluoromethoxy)-5-fluorophenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide Isomer 1	IC50	19.2 nM	US-10023539: Aryl-cyanoguanidine compounds
1-cyclopropyl-N-[1-[[1-[(4-fluorophenyl)methyl]pyrazol-4-yl]methyl]azetidin-3-yl]triazole-4-carboxamide	IC50	22 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[3-(4-Chloro-3-methylphenyl)-1-{N′-cyano-N-[3-(difluoromethoxy)phenyl]carbamimidoyl}-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-N2-methylglycinamide Isomer 2	IC50	22.9 nM	US-10023539: Aryl-cyanoguanidine compounds
N-cyclohexyl-3-[2-(3,4-dichlorophenyl)ethylamino]-N-[2-[[(2R)-2-hydroxy-2-(3-oxo-4H-1,4-benzoxazin-8-yl)ethyl]amino]ethyl]propanamide	IC50	23 nM	US-9598381: SMYD2 inhibitors
N-[1-[[1-[(3-chlorophenyl)methyl]pyrazol-4-yl]methyl]azetidin-3-yl]-1-cyclopropyltriazole-4-carboxamide	IC50	24 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
Rac-N-[1-(N′-cyano-N-{2-[(1-methylpiperidin-4-yl)oxy]-5-(trifluoromethyl)phenyl}-carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	IC50	26.1 nM	US-10023539: Aryl-cyanoguanidine compounds
5-cyclopropyl-N-[1-[1-(4-phenylmethoxyphenyl)ethyl]azetidin-3-yl]pyridazine-3-carboxamide	IC50	26.5 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
1-cyclopropyl-N-[1-[[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]methyl]azetidin-3-yl]triazole-4-carboxamide	IC50	28 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
1-cyclopropyl-N-[1-[[1-[(4-methylsulfanylphenyl)methyl]pyrazol-4-yl]methyl]azetidin-3-yl]triazole-4-carboxamide	IC50	28 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-{N′-cyano-N-[5-(difluoromethoxy)-2-methoxyphenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide Isomer 1	IC50	30 nM	US-10023539: Aryl-cyanoguanidine compounds
Rac-N-[1-{N′-cyano-N-[2-methoxy-5-(trifluoromethoxy)phenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	IC50	30.6 nM	US-10023539: Aryl-cyanoguanidine compounds
N-[1-{N′-cyano-N-[3-(difluoromethoxy)phenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-3-methyl-D-isovalinamide	IC50	32 nM	US-10023539: Aryl-cyanoguanidine compounds
N-[5-(4-chloro-3-methylphenyl)-2-[N-cyano-N’-[3-(difluoromethoxy)phenyl]carbamimidoyl]-3,4-dihydropyrazol-4-yl]-N-ethyl-2-(methylamino)acetamide	IC50	40.7 nM	US-10023539: Aryl-cyanoguanidine compounds
N-[1-[1-[2-chloro-3-(2-hydroxyethoxy)phenyl]ethyl]azetidin-3-yl]-5-cyclopropylpyridazine-3-carboxamide	IC50	41.6 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
1-cyclopropyl-N-[1-[(1R)-1-(2,3-dimethoxyphenyl)ethyl]azetidin-3-yl]triazole-4-carboxamide	IC50	44.3 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-[1-[2-chloro-3-(2-hydroxyethoxy)phenyl]ethyl]azetidin-3-yl]-1-cyclopropyltriazole-4-carboxamide	IC50	49.4 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-{N′-cyano-N-[3-(2,2,2-trifluoroethyl)phenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide Isomer 1	IC50	53 nM	US-10023539: Aryl-cyanoguanidine compounds
N-[1-[[1-[(4-tert-butylphenyl)methyl]pyrazol-4-yl]methyl]azetidin-3-yl]-1-cyclopropyltriazole-4-carboxamide	IC50	56 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-[(1S)-1-[2-chloro-3-(2-hydroxyethoxy)phenyl]ethyl]azetidin-3-yl]-1-cyclopropyltriazole-4-carboxamide	IC50	57.8 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
Rac-N-[1-(N′-cyano-N-{3-[2-(dimethylamino)ethoxy]phenyl}carbamimidoyl)-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethylglycinamide	IC50	59.5 nM	US-10023539: Aryl-cyanoguanidine compounds
Rac-N-[1-{N′-cyano-N-[3-(difluoromethoxy)-5-fluorophenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	IC50	63.1 nM	US-10023539: Aryl-cyanoguanidine compounds
Rac-N-[1-{N′-cyano-N-[3-(difluoromethoxy)-4-fluorophenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	IC50	64.8 nM	US-10023539: Aryl-cyanoguanidine compounds
N-[1-[(1-benzylpyrazol-4-yl)methyl]azetidin-3-yl]-5-cyclopropyl-1,3,4-oxadiazole-2-carboxamide	IC50	65 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-cyclohexyl-3-[2-(3,4-dichlorophenyl)ethylamino]-N-[2-[[(2S)-2-hydroxy-2-(3-oxo-4H-1,4-benzoxazin-8-yl)ethyl]amino]ethyl]propanamide	IC50	65 nM	US-9598381: SMYD2 inhibitors
Rac-N-[1-{N′-cyano-N-[3-(difluoromethoxy)-2-fluorophenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	IC50	67.4 nM	US-10023539: Aryl-cyanoguanidine compounds
N-[1-[1-[4-[(4-chlorophenyl)methoxy]phenyl]ethyl]azetidin-3-yl]-1-cyclopropyltriazole-4-carboxamide	IC50	69 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-[1-(2-chloro-3-methoxyphenyl)ethyl]azetidin-3-yl]-1-cyclopropyltriazole-4-carboxamide	IC50	69.5 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-[1-(2-chloro-3-methoxyphenyl)ethyl]azetidin-3-yl]-5-cyclopropylpyridazine-3-carboxamide	IC50	72 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-[(1-benzylpyrazol-4-yl)methyl]azetidin-3-yl]-5-cyclopropyl-1,3,4-thiadiazole-2-carboxamide	IC50	72 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-[(1-benzylpyrazol-4-yl)methyl]azetidin-3-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide	IC50	73 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-[(1-benzylpyrazol-4-yl)methyl]azetidin-3-yl]-1-cyclopropylimidazole-4-carboxamide	IC50	73 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer
N-[1-{N′-Cyano-N-[3-(difluoromethoxy)phenyl]carbamimidoyl}-3-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-4-yl]-N-ethyl-D-valinamide	IC50	73.5 nM	US-10023539: Aryl-cyanoguanidine compounds
N-[1-[[1-(1,3-benzothiazol-5-ylmethyl)pyrazol-4-yl]methyl]azetidin-3-yl]-1-cyclopropyltriazole-4-carboxamide	IC50	80 nM	US-10266526: Substituted 1,2,3-triazoles as SMYD inhibitors for treating cancer

ChEMBL bioactivities

201 potent at pChembl≥5 of 222 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.58	IC50	2.64	nM	CHEMBL5746366
8.55	IC50	2.8	nM	CHEMBL3590526
8.54	IC50	2.9	nM	CHEMBL5187983
8.52	IC50	3	nM	CHEMBL3819011
8.52	IC50	3	nM	CHEMBL5187983
8.41	IC50	3.9	nM	CHEMBL5187983
8.25	IC50	5.6	nM	CHEMBL3590527
8.22	IC50	6	nM	CHEMBL4536230
8.10	Ki	8	nM	CHEMBL3818617
8.10	IC50	8	nM	CHEMBL4520134
7.92	IC50	12	nM	CHEMBL4756148
7.88	IC50	13.2	nM	CHEMBL5789916
7.80	IC50	16	nM	CHEMBL4520134
7.80	IC50	16	nM	CHEMBL5197760
7.77	IC50	17	nM	CHEMBL4754902
7.77	IC50	17	nM	CHEMBL4798655
7.77	IC50	17	nM	CHEMBL3414623
7.72	IC50	19	nM	CHEMBL3818487
7.67	IC50	21.3	nM	CHEMBL5827171
7.64	IC50	23	nM	CHEMBL4449427
7.64	IC50	23	nM	CHEMBL4536230
7.63	IC50	23.6	nM	CHEMBL5827171
7.62	IC50	24	nM	CHEMBL4747370
7.57	IC50	27	nM	CHEMBL3818617
7.57	IC50	27	nM	CHEMBL4755178
7.57	IC50	27	nM	CHEMBL3818083
7.56	IC50	27.7	nM	CHEMBL5867448
7.55	Ki	28	nM	CHEMBL3818617
7.55	IC50	28	nM	CHEMBL4755178
7.54	IC50	28.7	nM	CHEMBL5867448
7.51	IC50	31	nM	CHEMBL4792378
7.51	IC50	31	nM	CHEMBL3414623
7.51	IC50	31	nM	CHEMBL5197760
7.50	IC50	32	nM	CHEMBL4590955
7.45	IC50	35.6	nM	CHEMBL5861178
7.43	IC50	37.2	nM	CHEMBL5861178
7.42	IC50	38	nM	CHEMBL3819284
7.42	IC50	38	nM	CHEMBL4763303
7.41	IC50	39	nM	CHEMBL4762851
7.40	IC50	40	nM	CHEMBL4439045
7.39	IC50	41	nM	CHEMBL4786535
7.36	IC50	44	nM	CHEMBL3818080
7.33	IC50	46.7	nM	CHEMBL3818083
7.32	IC50	48	nM	CHEMBL4777185
7.30	IC50	50	nM	CHEMBL3818322
7.30	IC50	50	nM	CHEMBL4753578
7.29	IC50	51	nM	CHEMBL2169920
7.28	IC50	53	nM	CHEMBL4792254
7.24	IC50	58	nM	CHEMBL4553357
7.24	IC50	57	nM	CHEMBL4761059

PubChem BioAssay actives

184 with measured affinity, of 450 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-cyclohexyl-3-[2-(3,4-dichlorophenyl)ethylamino]-N-[2-[[(2R)-2-hydroxy-2-(3-oxo-4H-1,4-benzoxazin-8-yl)ethyl]amino]ethyl]propanamide	1234041: Inhibition of SMYD2 (unknown origin) using biotinylated GSRAHSSHLKSKKGQSTSRH as substrate assessed as incorporation of tritium labeled methyl group from [3H]-SAM to biotinylated peptide substrate after 40 mins by scintillation proximity assay	ic50	0.0028	uM
N-[1-[[1-[(4-chlorophenyl)methyl]pyrazol-4-yl]methyl]azetidin-3-yl]-1-cyclopropyltriazole-4-carboxamide	1863586: Inhibition of human SMYD2 overexpressing human KYSE-150 cells assessed as SMYD2 assessed as reduction in BTF3 monomethylation by Western blot analysis	ic50	0.0029	uM
N-cyclohexyl-3-[2-(3,4-dichlorophenyl)ethylamino]-N-[2-[[(2R)-2-hydroxy-2-(5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl)ethyl]amino]ethyl]propanamide	1887903: Inhibition of SMYD2 (unknown origin) using 3H-SAM as substrate incubated for 1 hr by filter binding method	ic50	0.0030	uM
N-cyclohexyl-3-[2-(3,4-dichlorophenyl)ethylamino]-N-[2-[[(2S)-2-hydroxy-2-(3-oxo-4H-1,4-benzoxazin-8-yl)ethyl]amino]ethyl]propanamide	1234041: Inhibition of SMYD2 (unknown origin) using biotinylated GSRAHSSHLKSKKGQSTSRH as substrate assessed as incorporation of tritium labeled methyl group from [3H]-SAM to biotinylated peptide substrate after 40 mins by scintillation proximity assay	ic50	0.0056	uM
[3-(6-amino-2-methylpurin-9-yl)azetidin-1-yl]-[1-[(1-cyclohept-2-en-1-ylpiperidin-4-yl)methyl]pyrrol-3-yl]methanone	1577889: Inhibition of recombinant human SMYD2 (1 to 433 residues) expressed in baculovirus infected Sf9 insect cells using biotinylated-p53 peptide (361 to 380 residues) as substrate measured after 50 mins in presence of 70 nM [3H]-SAM by scintillation proximity assay	ic50	0.0060	uM
N-[(4S)-2-[N-cyano-N’-[3-(difluoromethoxy)phenyl]carbamimidoyl]-5-(3,4-dichlorophenyl)-3,4-dihydropyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	1308114: Competitive inhibition of full length 6xHis-tagged SMYD2 (unknown origin) expressed in Escherichia coli using varying levels of Btn-Ahx-GSRAHSSHLKSKKGQSTSRH-amide substrate after 30 mins in presence of fixed 3H-SAM level by scintillation proximity assay	ki	0.0080	uM
[3-(4-amino-6-methylimidazo[4,5-c]pyridin-1-yl)-3-methylazetidin-1-yl]-[1-[[1-[(1R)-cyclohept-2-en-1-yl]piperidin-4-yl]methyl]pyrrol-3-yl]methanone	1577889: Inhibition of recombinant human SMYD2 (1 to 433 residues) expressed in baculovirus infected Sf9 insect cells using biotinylated-p53 peptide (361 to 380 residues) as substrate measured after 50 mins in presence of 70 nM [3H]-SAM by scintillation proximity assay	ic50	0.0080	uM
5-[2-[1-[2-(3,4-dichlorophenyl)ethyl]azetidin-3-yl]oxyphenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.0120	uM
3-cyano-5-[2-[4-[2-(3-methylindol-1-yl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)benzamide	1199201: Inhibition of SMYD2 (unknown origin)	ic50	0.0150	uM
N-[1-[(1-benzylpyrazol-4-yl)methyl]azetidin-3-yl]-1-cyclopropyltriazole-4-carboxamide	1863585: Inhibition of FLAG and C-terminally Avi-tagged full length SMYD2 (unknown origin) expressed in Sf9 cells using SAM and histone H3 (1 to 29 residues) as peptide substrate preincubated for 30 mins followed by substrate addition by radiometric assay	ic50	0.0160	uM
5-[2-[4-[2-(1H-indol-3-yl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.0170	uM
5-[2-[4-[2-(3,4-dichlorophenyl)acetyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1698453: Inhibition of SMYD2 (unknown origin) transfected in human U2OS cells assessed as inhibition of methylation of monomethyl p53 peptide incubated for 24 hrs by immunofluorescence assay	ic50	0.0170	uM
N-[(4S)-2-[N-cyano-N’-[3-(difluoromethoxy)-5-fluorophenyl]carbamimidoyl]-5-(3,4-dichlorophenyl)-3,4-dihydropyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	1308097: Inhibition of full length 6xHis-tagged SMYD2 (unknown origin) expressed in Escherichia coli using Btn-Ahx GSRAHSSHLKSKKGQSTSRH-amide as substrate after 30 mins in presence 3H-SAM of by scintillation proximity assay	ic50	0.0190	uM
[3-(6-amino-2-methylpurin-9-yl)azetidin-1-yl]-[1-[(1-cycloheptylpiperidin-4-yl)methyl]pyrrol-3-yl]methanone	1577889: Inhibition of recombinant human SMYD2 (1 to 433 residues) expressed in baculovirus infected Sf9 insect cells using biotinylated-p53 peptide (361 to 380 residues) as substrate measured after 50 mins in presence of 70 nM [3H]-SAM by scintillation proximity assay	ic50	0.0230	uM
5-[2-[4-[3-(3,4-dichlorophenyl)propanoyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1698453: Inhibition of SMYD2 (unknown origin) transfected in human U2OS cells assessed as inhibition of methylation of monomethyl p53 peptide incubated for 24 hrs by immunofluorescence assay	ic50	0.0240	uM
N-[2-[N-cyano-N’-[3-(difluoromethoxy)phenyl]carbamimidoyl]-5-(3,4-dichlorophenyl)-3,4-dihydropyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	1887903: Inhibition of SMYD2 (unknown origin) using 3H-SAM as substrate incubated for 1 hr by filter binding method	ic50	0.0270	uM
3-cyano-5-[2-[4-[2-(1H-indol-3-yl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)benzamide	1845922: Inhibition of SMYD2 (unknown origin)	ic50	0.0270	uM
3-cyano-5-[2-[4-[2-(3-methylphenyl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)benzamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.0310	uM
[3-(6-amino-2-methylpurin-9-yl)azetidin-1-yl]-[5-[(1-cycloheptylpiperidin-4-yl)methyl]-1-methylpyrazol-3-yl]methanone	1577889: Inhibition of recombinant human SMYD2 (1 to 433 residues) expressed in baculovirus infected Sf9 insect cells using biotinylated-p53 peptide (361 to 380 residues) as substrate measured after 50 mins in presence of 70 nM [3H]-SAM by scintillation proximity assay	ic50	0.0320	uM
N-[(4S)-5-(4-chloro-3-methylphenyl)-2-[N-cyano-N’-[3-(difluoromethoxy)phenyl]carbamimidoyl]-3,4-dihydropyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	1308097: Inhibition of full length 6xHis-tagged SMYD2 (unknown origin) expressed in Escherichia coli using Btn-Ahx GSRAHSSHLKSKKGQSTSRH-amide as substrate after 30 mins in presence 3H-SAM of by scintillation proximity assay	ic50	0.0380	uM
5-[2-[4-[2-(3,4-dichlorophenyl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.0380	uM
5-[2-[4-[(3-methoxyphenyl)methylamino]piperidin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.0390	uM
[3-(6-amino-2-methylpurin-9-yl)azetidin-1-yl]-[5-[(4-cycloheptylpiperazin-1-yl)methyl]-1-methylpyrazol-3-yl]methanone	1577889: Inhibition of recombinant human SMYD2 (1 to 433 residues) expressed in baculovirus infected Sf9 insect cells using biotinylated-p53 peptide (361 to 380 residues) as substrate measured after 50 mins in presence of 70 nM [3H]-SAM by scintillation proximity assay	ic50	0.0400	uM
3-[2-[4-[2-(1H-indol-3-yl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)benzamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.0410	uM
N-[(4S)-2-[N’-[4-chloro-3-(difluoromethoxy)phenyl]-N-cyanocarbamimidoyl]-5-(3,4-dichlorophenyl)-3,4-dihydropyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	1308097: Inhibition of full length 6xHis-tagged SMYD2 (unknown origin) expressed in Escherichia coli using Btn-Ahx GSRAHSSHLKSKKGQSTSRH-amide as substrate after 30 mins in presence 3H-SAM of by scintillation proximity assay	ic50	0.0440	uM
5-[2-[1-[2-(3,4-dichlorophenyl)acetyl]azetidin-3-yl]oxyphenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1698453: Inhibition of SMYD2 (unknown origin) transfected in human U2OS cells assessed as inhibition of methylation of monomethyl p53 peptide incubated for 24 hrs by immunofluorescence assay	ic50	0.0480	uM
N-[(4S)-2-[N-cyano-N’-[3-(trifluoromethoxy)phenyl]carbamimidoyl]-5-(3,4-dichlorophenyl)-3,4-dihydropyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	1308097: Inhibition of full length 6xHis-tagged SMYD2 (unknown origin) expressed in Escherichia coli using Btn-Ahx GSRAHSSHLKSKKGQSTSRH-amide as substrate after 30 mins in presence 3H-SAM of by scintillation proximity assay	ic50	0.0500	uM
5-[2-[4-[2-(1H-indol-3-yl)acetyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1698453: Inhibition of SMYD2 (unknown origin) transfected in human U2OS cells assessed as inhibition of methylation of monomethyl p53 peptide incubated for 24 hrs by immunofluorescence assay	ic50	0.0500	uM
N-cyclohexyl-3-[2-(3,4-dichlorophenyl)ethylamino]-N-[2-[2-(5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl)ethylamino]ethyl]propanamide	2163210: Inhibition of SMYD2 (unknown origin) using N-terminal GST-tagged MAP3K2 and 3H-SAM as substrate for 2 hrs by TopCount NXT plate reader	ic50	0.0510	uM
5-[2-[4-(3-methylindol-1-yl)butylcarbamoyl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1698453: Inhibition of SMYD2 (unknown origin) transfected in human U2OS cells assessed as inhibition of methylation of monomethyl p53 peptide incubated for 24 hrs by immunofluorescence assay	ic50	0.0530	uM
5-[2-[1-[3-(3,4-dichlorophenyl)propanoyl]azetidin-3-yl]oxyphenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1698453: Inhibition of SMYD2 (unknown origin) transfected in human U2OS cells assessed as inhibition of methylation of monomethyl p53 peptide incubated for 24 hrs by immunofluorescence assay	ic50	0.0570	uM
5-[2-[4-[2-amino-3-(1H-indol-3-yl)propanoyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1698453: Inhibition of SMYD2 (unknown origin) transfected in human U2OS cells assessed as inhibition of methylation of monomethyl p53 peptide incubated for 24 hrs by immunofluorescence assay	ic50	0.0570	uM
[3-(6-amino-2-methylpurin-9-yl)-3-methylazetidin-1-yl]-[5-[(4-cycloheptylpiperazin-1-yl)methyl]-1-methylpyrazol-3-yl]methanone	1577889: Inhibition of recombinant human SMYD2 (1 to 433 residues) expressed in baculovirus infected Sf9 insect cells using biotinylated-p53 peptide (361 to 380 residues) as substrate measured after 50 mins in presence of 70 nM [3H]-SAM by scintillation proximity assay	ic50	0.0580	uM
3-cyano-5-[2-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)benzamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.0590	uM
2-[2-[4-[2-(1H-indol-3-yl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-4-carboxamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.0620	uM
6-[2-[4-[2-(3,4-dichlorophenyl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)-1H-pyrazolo[5,4-b]pyridine-4-carboxamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.0650	uM
N-[(4S)-2-[N-cyano-N’-(3-methoxyphenyl)carbamimidoyl]-5-(3,4-dichlorophenyl)-3,4-dihydropyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	1308097: Inhibition of full length 6xHis-tagged SMYD2 (unknown origin) expressed in Escherichia coli using Btn-Ahx GSRAHSSHLKSKKGQSTSRH-amide as substrate after 30 mins in presence 3H-SAM of by scintillation proximity assay	ic50	0.0710	uM
5-[2-(4-indol-1-ylbutylcarbamoyl)phenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1698453: Inhibition of SMYD2 (unknown origin) transfected in human U2OS cells assessed as inhibition of methylation of monomethyl p53 peptide incubated for 24 hrs by immunofluorescence assay	ic50	0.0750	uM
N-[5-(4-chloro-3-methylphenyl)-2-[N-cyano-N’-[3-(difluoromethoxy)phenyl]carbamimidoyl]-3,4-dihydropyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	1308097: Inhibition of full length 6xHis-tagged SMYD2 (unknown origin) expressed in Escherichia coli using Btn-Ahx GSRAHSSHLKSKKGQSTSRH-amide as substrate after 30 mins in presence 3H-SAM of by scintillation proximity assay	ic50	0.0800	uM
5-[2-[1-[2-(3,4-dichlorophenyl)acetyl]piperidin-4-yl]oxyphenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-3-carboxamide	1698453: Inhibition of SMYD2 (unknown origin) transfected in human U2OS cells assessed as inhibition of methylation of monomethyl p53 peptide incubated for 24 hrs by immunofluorescence assay	ic50	0.0810	uM
3-[2-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)benzamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.1140	uM
N-[(4S)-2-[N-cyano-N’-[6-(difluoromethoxy)-2-pyridinyl]carbamimidoyl]-5-(3,4-dichlorophenyl)-3,4-dihydropyrazol-4-yl]-N-ethyl-2-hydroxyacetamide	1308097: Inhibition of full length 6xHis-tagged SMYD2 (unknown origin) expressed in Escherichia coli using Btn-Ahx GSRAHSSHLKSKKGQSTSRH-amide as substrate after 30 mins in presence 3H-SAM of by scintillation proximity assay	ic50	0.1190	uM
2-[2-[4-[2-(3,4-dichlorophenyl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-4-carboxamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.1200	uM
3-cyano-5-[2-[4-[2-(3,4-dichlorophenyl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)benzamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.1380	uM
3-[2-[4-[2-(3,4-dichlorophenyl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)benzamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.1650	uM
(2S)-2-amino-4-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]butanoic acid	1192336: Inhibition of SMYD2 (unknown origin) by HMT assay	ic50	0.1800	uM
3-[2-[4-[2-(3-methylphenyl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)benzamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.2110	uM
3-[2-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)benzamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.2730	uM
2-[2-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)pyridine-4-carboxamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.3050	uM
3-[2-[4-(2-phenylethyl)piperazin-1-yl]phenyl]-N-(3-pyrrolidin-1-ylpropyl)benzamide	1686710: Inhibition of SMYD2 (unknown origin)	ic50	0.3390	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	8
bisphenol A	affects expression, decreases expression	3
trichostatin A	affects cotreatment, increases expression	3
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
LLY-507	affects binding, decreases activity	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
AZ 505	decreases activity, affects binding	1
Acetaminophen	decreases expression	1
Ethanol	decreases expression	1
Carbamazepine	affects expression	1
Coumestrol	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1

ChEMBL screening assays

148 unique, capped per target: 148 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2173264	Binding	Competitive binding affinity to full length human SMYD2 amino acid 1 to 433 expressed in Escherichia coli BL21 (DE3) after 90 mins by radioactive filter-binding assay in presence of P53 peptide	Oncoepigenomics: making histone lysine methylation count. — Eur J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7ZH	Abcam Raji SMYD2 KO	Cancer cell line	Male
CVCL_C0AA	Abcam THP-1 SMYD2 KO	Cancer cell line	Male
CVCL_C7BY	Abcam PC-3 SMYD2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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