MYLK3

gene
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Also known as caMLCKMLCK

Summary

MYLK3 (myosin light chain kinase 3, HGNC:29826) is a protein-coding gene on chromosome 16q11.2, encoding Myosin light chain kinase 3 (Q32MK0). Kinase that phosphorylates MYL2 in vitro.

Phosphorylation of cardiac myosin heavy chains (see MYH7B, MIM 609928) and light chains (see MYL2, MIM 160781) by a kinase, such as MYLK3, potentiates the force and rate of cross-bridge recruitment in cardiac myocytes (Chan et al., 2008 [PubMed 18202317]).

Source: NCBI Gene 91807 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): dilated cardiomyopathy (Moderate, ClinGen)
  • Clinical variants (ClinVar): 1,054 total — 1 likely-pathogenic
  • Phenotypes (HPO): 1
  • Druggable target: yes — 24 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_182493

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:29826
Approved symbolMYLK3
Namemyosin light chain kinase 3
Location16q11.2
Locus typegene with protein product
StatusApproved
AliasescaMLCK, MLCK
Ensembl geneENSG00000140795
Ensembl biotypeprotein_coding
OMIM612147
Entrez91807

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000394809, ENST00000536476, ENST00000562104, ENST00000564731, ENST00000565182, ENST00000569810, ENST00000569844, ENST00000874186, ENST00000874187, ENST00000971334

RefSeq mRNA: 2 — MANE Select: NM_182493 NM_001308301, NM_182493

CCDS: CCDS10723, CCDS76861

Canonical transcript exons

ENST00000394809 — 13 exons

ExonStartEnd
ENSE000009450624674771746748344
ENSE000009450644673771146738143
ENSE000009450704672112346721193
ENSE000009450714671264846712776
ENSE000009450764672723646727377
ENSE000026030724670228246707763
ENSE000035427724674005746740147
ENSE000035740184670953946709671
ENSE000036063764673059346730698
ENSE000036064734673220846732668
ENSE000036196564671063746710789
ENSE000036305624672902446729133
ENSE000036725144672959446729687

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 98.13.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.3151 / max 334.2785, expressed in 114 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter IDTPM avgSamples expressed
1572200.565065
1572100.559744
1572180.062725
1572170.038317
2078640.034213
1572190.033221
1572090.01143
1572160.01069

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
cardiac muscle of right atriumUBERON:000337998.13gold quality
myocardiumUBERON:000234997.63gold quality
heart right ventricleUBERON:000208097.45gold quality
left ventricle myocardiumUBERON:000656697.07gold quality
cardiac atriumUBERON:000208195.61gold quality
right atrium auricular regionUBERON:000663195.22gold quality
cardiac ventricleUBERON:000208294.18gold quality
heart left ventricleUBERON:000208494.08gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450293.96gold quality
body of tongueUBERON:001187693.42gold quality
apex of heartUBERON:000209892.99gold quality
biceps brachiiUBERON:000150792.25gold quality
diaphragmUBERON:000110391.94gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451191.30gold quality
triceps brachiiUBERON:000150990.41gold quality
heartUBERON:000094890.00gold quality
vena cavaUBERON:000408789.87gold quality
vastus lateralisUBERON:000137989.44gold quality
skeletal muscle tissueUBERON:000113488.42gold quality
buccal mucosa cellCL:000233688.40gold quality
quadriceps femorisUBERON:000137788.36gold quality
muscle tissueUBERON:000238587.30gold quality
hindlimb stylopod muscleUBERON:000425285.11gold quality
deltoidUBERON:000147684.99silver quality
renal glomerulusUBERON:000007484.75gold quality
gluteal muscleUBERON:000200083.52silver quality
muscle organUBERON:000163083.44gold quality
metanephric glomerulusUBERON:000473683.17gold quality
tibialis anteriorUBERON:000138582.62silver quality
muscle of legUBERON:000138381.23gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes5.65
E-HCAD-5no226.97

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NKX2-5

miRNA regulators (miRDB)

167 targeting MYLK3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-6867-5P100.0082.213464
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-4668-3P100.0068.742635
HSA-MIR-6851-5P100.0065.631294
HSA-MIR-3689D100.0066.141181
HSA-MIR-3646100.0073.565283
HSA-MIR-3163100.0077.238605
HSA-MIR-8485100.0077.574731
HSA-MIR-6833-3P100.0070.633197
HSA-MIR-4768-5P100.0069.492861
HSA-MIR-7110-3P100.0073.182486
HSA-MIR-4481100.0066.421669
HSA-MIR-6873-3P100.0071.422626
HSA-MIR-371B-5P99.9975.344759
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-428299.9975.366408
HSA-MIR-150-5P99.9966.691976
HSA-MIR-373-5P99.9875.364753
HSA-MIR-616-5P99.9875.584775
HSA-MIR-806899.9873.852376
HSA-MIR-1213699.9872.815713
HSA-MIR-477599.9875.006394
HSA-MIR-569699.9872.364487
HSA-MIR-6891-5P99.9866.531372
HSA-MIR-60799.9773.625593
HSA-MIR-314899.9775.066478
HSA-MIR-590-3P99.9674.346478
HSA-MIR-365899.9673.874379
HSA-MIR-6778-3P99.9667.292693
HSA-MIR-548AA99.9670.643753

Literature-anchored findings (GeneRIF, showing 6)

  • Integrated cDNA expression analysis of failing human myocardia uncovered a novel protein kinase, cardiac-specific myosin light chain kinase (cardiac-MLCK), which acts on MLC2v. (PMID:17885681)
  • data indicate that the IL-1beta-induced increase in MLCK protein expression and Caco-2 TJ permeability was mediated by an increase in MLCK expression and activity and by an NF-kappaB-dependent increase in MLCK gene transcription (PMID:18390750)
  • These findings suggest that hepatitis B virus X protein disrupts stress fiber formation and triggers apoptosis via an MLCK and a PTEN-dependent pathway. (PMID:23591626)
  • Biochemical and physiological regulation of cardiac myocyte contraction by cardiac-specific myosin light chain kinase. (PMID:23863751)
  • This study demonstrates that cyclic stretch disrupts tight junctions and adherens junctions by a JNK2, c-Src, and MLCK-dependent mechanism. (PMID:24722904)
  • Study identified MYLK3 mutations associated with familial dilated cardiomyopathy. In vitro experiments and immunohistochemistry suggested that the MYLK3 mutations identified in this study result in markedly reduced levels of protein expression and myosin light chain 2 phosphorylation. (PMID:29235529)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriomylk3ENSDARG00000076348
mus_musculusMylk3ENSMUSG00000031698
rattus_norvegicusMylk3ENSRNOG00000017546

Paralogs (22): CAMKK1 (ENSG00000004660), CAMK1G (ENSG00000008118), CAMK2B (ENSG00000058404), CAMK2A (ENSG00000070808), MYLK2 (ENSG00000101306), CAMKK2 (ENSG00000110931), STK11 (ENSG00000118046), STK33 (ENSG00000130413), PNCK (ENSG00000130822), DCLK1 (ENSG00000133083), CAMK1 (ENSG00000134072), CAMK2D (ENSG00000145349), MYLK4 (ENSG00000145949), PSKH2 (ENSG00000147613), CAMK2G (ENSG00000148660), PHKG2 (ENSG00000156873), PSKH1 (ENSG00000159792), DCLK3 (ENSG00000163673), CAMKV (ENSG00000164076), PHKG1 (ENSG00000164776), DCLK2 (ENSG00000170390), CAMK1D (ENSG00000183049)

Protein

Protein identifiers

Myosin light chain kinase 3Q32MK0 (reviewed: Q32MK0)

Alternative names: Cardiac-MyBP-C-associated Ca/CaM kinase

All UniProt accessions (1): Q32MK0

UniProt curated annotations — full annotation on UniProt →

Function. Kinase that phosphorylates MYL2 in vitro. Promotes sarcomere formation in cardiomyocytes and increases cardiomyocyte contractility.

Subcellular location. Cytoplasm.

Tissue specificity. Restricted to heart.

Post-translational modifications. Phosphorylated on serine residues.

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

Isoforms (2)

UniProt IDNamesCanonical?
Q32MK0-31yes
Q32MK0-42

RefSeq proteins (2): NP_001295230, NP_872299* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000719Prot_kinase_domDomain
IPR008271Ser/Thr_kinase_ASActive_site
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR017441Protein_kinase_ATP_BSBinding_site

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

  • L-seryl-[myosin light chain] + ATP = O-phospho-L-seryl-[myosin light chain] + ADP + H(+) (RHEA:22004)
  • L-threonyl-[myosin light chain] + ATP = O-phospho-L-threonyl-[myosin light chain] + ADP + H(+) (RHEA:53900)

UniProt features (21 total): modified residue 4, sequence variant 3, region of interest 3, compositionally biased region 3, binding site 2, sequence conflict 2, chain 1, domain 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q32MK0-F163.260.29

Functional residue map

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

Catalytic / active sites (1): 636 (proton acceptor)

Ligand- & substrate-binding residues (2): 544; 521–529

Post-translational modifications (4): 152, 355, 401, 408

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 132 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_CARDIAC_MYOFIBRIL_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_SARCOMERE_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, TGCTGAY_UNKNOWN

GO Biological Process (9): signal transduction (GO:0007165), sarcomere organization (GO:0045214), sarcomerogenesis (GO:0048769), cardiac myofibril assembly (GO:0055003), positive regulation of sarcomere organization (GO:0060298), cellular response to interleukin-1 (GO:0071347), positive regulation of tight junction disassembly (GO:1905075), positive regulation of membrane permeability (GO:1905710), protein phosphorylation (GO:0006468)

GO Molecular Function (9): calcium/calmodulin-dependent protein kinase activity (GO:0004683), myosin light chain kinase activity (GO:0004687), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), actin cytoskeleton (GO:0015629)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
myofibril assembly3
actomyosin structure organization2
protein serine/threonine kinase activity2
cellular anatomical structure2
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
cardiac muscle cell development1
sarcomere organization1
positive regulation of striated muscle cell differentiation1
positive regulation of cytoskeleton organization1
regulation of sarcomere organization1
positive regulation of supramolecular fiber organization1
response to interleukin-11
cellular response to cytokine stimulus1
positive regulation of cellular component organization1
tight junction disassembly1
regulation of tight junction disassembly1
regulation of membrane permeability1
phosphorylation1
protein modification process1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
nucleoside phosphate binding1
heterocyclic compound binding1
kinase activity1
phosphotransferase activity, alcohol group as acceptor1
catalytic activity, acting on a protein1
protein kinase activity1
binding1
transferase activity, transferring phosphorus-containing groups1
catalytic activity1
intracellular anatomical structure1
cytoplasm1
cytoskeleton1

Protein interactions and networks

STRING

1533 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
MYLK3CALML3P27482964
MYLK3CALML5Q9NZT1964
MYLK3CALML6Q8TD86962
MYLK3CALML4Q96GE6962
MYLK3CALM1P02593928
MYLK3MYL7Q01449825
MYLK3MYL2P10916791
MYLK3MYH7BA7E2Y1760
MYLK3PPP1R12AO14974727
MYLK3MYL12BO14950657
MYLK3RHOAP06749640
MYLK3PPP1R14AQ96A00609
MYLK3ACTC1P04270599
MYLK3MYL9P24844586
MYLK3PAK1Q13153456

IntAct

14 interactions, top by confidence:

ABTypeScore
MAPK14RPS6KA5psi-mi:“MI:0914”(association)0.660
MAPK12MAPK13psi-mi:“MI:0914”(association)0.640
MYLK3YWHAEpsi-mi:“MI:0915”(physical association)0.400
SFNMYLK3psi-mi:“MI:0915”(physical association)0.400
HSP90AB1MYLK3psi-mi:“MI:0915”(physical association)0.400
ALBCNOT1psi-mi:“MI:0914”(association)0.350
MAPK14PRKYpsi-mi:“MI:0914”(association)0.350
MYLK3psi-mi:“MI:0914”(association)0.350
MYLK3OBSL1psi-mi:“MI:0914”(association)0.350

BioGRID (17): MYLK3 (Affinity Capture-MS), MYLK3 (Affinity Capture-MS), MYLK3 (Affinity Capture-MS), MYLK3 (Affinity Capture-MS), CALM3 (Affinity Capture-MS), OBSL1 (Affinity Capture-MS), PCDHB11 (Affinity Capture-MS), PCDHB5 (Affinity Capture-MS), OBSL1 (Affinity Capture-MS), MYLK3 (Affinity Capture-MS), CALM3 (Affinity Capture-MS), MYLK3 (Affinity Capture-MS), RBM17 (Cross-Linking-MS (XL-MS)), MYLK3 (Affinity Capture-RNA), MYLK3 (Dosage Lethality)

ESM2 similar proteins: A4IFM7, A8C984, B6D5P1, B6D5P6, E9PT87, O08815, O54988, O55092, O70551, O88831, P00519, P00520, P00521, P07313, P0C865, P13234, P20689, P42684, P46087, Q13164, Q14028, Q16566, Q2KI23, Q32MK0, Q3SYS4, Q3UH66, Q3UIZ8, Q3ULB5, Q4JIM5, Q4KMM3, Q4V8B0, Q5R8Z4, Q5RDG7, Q5TGJ6, Q63553, Q6AYH9, Q6PDI6, Q80XI3, Q8BHL3, Q8BWQ5

Diamond homologs: A0A509AFG4, A0A5K1K8H0, A2AAJ9, A2ZVI7, A4IFM7, A8C984, A8WXF6, B9FKW9, C0HKC8, C0HKC9, E9PT87, O02827, O43293, O44997, O54784, O62305, O70150, O75147, O80673, O88764, O94768, P07313, P08414, P11801, P13234, P15735, P18653, P20689, P29294, P31325, P34101, P43292, P53355, P53681, Q00168, Q00771, Q0KHT7, Q0V7M1, Q10KY3, Q14012

SIGNOR signaling

1 interactions.

AEffectBMechanism
MYLK3“up-regulates activity”MEF2Cphosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 11 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO termPartnersFoldFDR
intracellular signal transduction519.1×5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1054 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic1
Uncertain significance657
Likely benign341
Benign21

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
2419098NM_182493.3(MYLK3):c.1915-1G>TLikely pathogenic

SpliceAI

2278 predictions. Top by Δscore:

VariantEffectΔscore
16:46712644:TCACA:Tdonor_loss1.0000
16:46712645:CA:Cdonor_loss1.0000
16:46712646:A:ACdonor_gain1.0000
16:46712647:C:CCdonor_gain1.0000
16:46712647:CAG:Cdonor_gain1.0000
16:46712647:CAGCA:Cdonor_gain1.0000
16:46727231:CCCA:Cdonor_loss1.0000
16:46727232:CCA:Cdonor_loss1.0000
16:46727233:CA:Cdonor_loss1.0000
16:46727234:ACC:Adonor_loss1.0000
16:46727235:C:Adonor_loss1.0000
16:46729020:TCACT:Tdonor_loss1.0000
16:46729021:CA:Cdonor_loss1.0000
16:46729022:A:ACdonor_gain1.0000
16:46729022:ACT:Adonor_loss1.0000
16:46729023:C:CAdonor_gain1.0000
16:46729023:C:CTdonor_loss1.0000
16:46729023:CT:Cdonor_gain1.0000
16:46729023:CTA:Cdonor_gain1.0000
16:46729023:CTACT:Cdonor_gain1.0000
16:46729028:C:CAdonor_gain1.0000
16:46729145:C:CTacceptor_gain1.0000
16:46729145:C:Tacceptor_gain1.0000
16:46729146:A:Tacceptor_gain1.0000
16:46740145:ATTC:Aacceptor_loss1.0000
16:46740146:TT:Tacceptor_gain1.0000
16:46740148:C:CCacceptor_gain1.0000
16:46740148:CTA:Cacceptor_loss1.0000
16:46709541:T:TAdonor_gain0.9900
16:46711401:C:CTacceptor_gain0.9900

AlphaMissense

5352 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
16:46712676:A:GW696R1.000
16:46712676:A:TW696R1.000
16:46712728:G:CF678L1.000
16:46712728:G:TF678L1.000
16:46712730:A:GF678L1.000
16:46721141:T:AD656V1.000
16:46727246:A:GL635P1.000
16:46709634:A:GW769R0.999
16:46709634:A:TW769R0.999
16:46709665:T:AR758S0.999
16:46709665:T:GR758S0.999
16:46709666:C:GR758T0.999
16:46712667:C:GG699R0.999
16:46712667:C:TG699R0.999
16:46712671:A:CS697R0.999
16:46712671:A:TS697R0.999
16:46712673:T:GS697R0.999
16:46712674:C:AW696C0.999
16:46712674:C:GW696C0.999
16:46712682:C:AD694Y0.999
16:46712682:C:GD694H0.999
16:46712696:A:TV689D0.999
16:46712711:A:TV684D0.999
16:46712729:A:GF678S0.999
16:46712741:C:TG674D0.999
16:46721129:G:TA660D0.999
16:46721140:G:CD656E0.999
16:46721140:G:TD656E0.999
16:46721141:T:CD656G0.999
16:46721141:T:GD656A0.999

dbSNP variants (sampled 300 via entrez): RS1000020905 (16:46754710 C>A,T), RS1000041279 (16:46720036 C>A,G,T), RS1000071844 (16:46702168 T>C), RS1000072529 (16:46720449 C>T), RS1000077140 (16:46762495 G>A), RS1000147805 (16:46739550 C>T), RS1000184620 (16:46752682 T>C), RS1000221747 (16:46737417 C>A,T), RS1000234971 (16:46719824 C>T), RS1000248810 (16:46764587 A>C,T), RS1000259215 (16:46743790 G>A,T), RS1000280371 (16:46743310 A>G), RS1000309875 (16:46726948 C>T), RS1000339893 (16:46713724 C>T), RS1000448378 (16:46752095 G>A)

Disease associations

OMIM: gene MIM:612147 | disease phenotypes: MIM:614203, MIM:115200

GenCC curated gene-disease

DiseaseClassificationInheritance
dilated cardiomyopathyModerateAutosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

DiseaseClassificationInheritance
dilated cardiomyopathyModerateAD

Mondo (3): Parkinson disease 17 (MONDO:0013625), dilated cardiomyopathy (MONDO:0005021), familial dilated cardiomyopathy (MONDO:0016333)

Orphanet (3): Hereditary late-onset Parkinson disease (Orphanet:411602), Dilated cardiomyopathy (Orphanet:217604), Familial dilated cardiomyopathy (Orphanet:217607)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPOTerm
HP:0001644Dilated cardiomyopathy

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

DescriptorNameTree numbers
D002311Cardiomyopathy, DilatedC14.280.195.160; C14.280.238.070; C16.320.488.750
C536231familial dilated cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4627 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

24 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 224,246 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1287853FEDRATINIB43,554
CHEMBL1289926AXITINIB415,732
CHEMBL1336SORAFENIB486,060
CHEMBL502835NINTEDANIB48,545
CHEMBL535SUNITINIB479,020
CHEMBL576982QUIZARTINIB44,432
CHEMBL608533MIDOSTAURIN47,259
CHEMBL522892DOVITINIB34,944
CHEMBL603469LESTAURTINIB3
CHEMBL1230609FORETINIB23,096
CHEMBL1614713CC-4012389
CHEMBL1721885SU-0148132363
CHEMBL2386889SCH-9007762740
CHEMBL3218578BGT-226 FREE BASE22,878
CHEMBL495727AT-928321,376
CHEMBL564829MILCICLIB2821
CHEMBL572878TOZASERTIB22,998
CHEMBL1090479GSK-10709161177
CHEMBL1908397KW-24491622
CHEMBL2041933AZD-776211,240
CHEMBL296468BMS-3870321
CHEMBL3128043PF-037583091
CHEMBL3545328XL-0191
CHEMBL4289017PF-038147351

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Myosin Light Chain Kinase (MLCK) family

Binding affinities (BindingDB)

6 measured of 8 human assays (8 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
StaurosporineKD1.7 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyrilKD520 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamideKD1100 nM
BMS-387072KD1800 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamideKD2600 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamideKD3500 nM

ChEMBL bioactivities

46 potent at pChembl≥5 of 47 total, top 45 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.70Kd2nMDOVITINIB
8.37Kd4.3nMKW-2449
7.92Kd12nMLESTAURTINIB
7.82Kd15nMTOZASERTIB
7.70Kd20nMSU-014813
7.64Kd23nMSUNITINIB
7.51Kd31nMCHEMBL3990456
7.38Kd42nMSU-014813
7.38Kd42nMCHEMBL1908395
7.02Kd95nMLESTAURTINIB
7.01Kd98nMK-252A
7.01Kd98nMXL-019
6.98Kd104nMGSK-1070916
6.96Kd109nMPF-03814735
6.96Kd110nMNINTEDANIB
6.93IC50118nMSTAUROSPORINE
6.89Kd129nMAT-9283
6.89IC50129nMSTAUROSPORINE
6.85Kd140nMCHEMBL386051
6.85Kd140nMSTAUROSPORINE
6.84Kd146nMCHEMBL4465866
6.73IC50188nMSTAUROSPORINE
6.72Kd189nMSCH-900776
6.54Kd284.9nMCHEMBL5653589
6.49ED50327.4nMCHEMBL5653589
6.46Kd349nMPF-03758309
6.46Kd350nMMILCICLIB
6.44Kd360nMCHEMBL1241674
6.40Kd400nMCHEMBL379218
6.39Kd410nMQUIZARTINIB
6.32Kd483nMCC-401
6.00IC501000nMTP-030-1
6.00IC501000nMTP-030-2
6.00IC501000nMTP-030n
5.96Kd1105nMBGT-226 FREE BASE
5.77Kd1700nMBMS-387032
5.77Kd1700nMAXITINIB
5.64Kd2300nMMIDOSTAURIN
5.53Kd2939nMNMS-1286937
5.52Kd3000nMFORETINIB
5.44Kd3647nMAZD-7762
5.41Kd3904nMAXITINIB
5.25Kd5600nMQUIZARTINIB
5.02Kd9600nMSORAFENIB
5.01Kd9700nMFEDRATINIB

PubChem BioAssay actives

42 with measured affinity, of 392 total; 34 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one624738: Binding constant for MLCK kinase domainkd0.0020uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone624738: Binding constant for MLCK kinase domainkd0.0043uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one624738: Binding constant for MLCK kinase domainkd0.0120uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.0150uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.0200uM
Sunitinib624738: Binding constant for MLCK kinase domainkd0.0230uM
2-amino-2-cyclohexyl-N-[2-(1-methylpyrazol-4-yl)-9-oxo-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl]acetamide1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.0310uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride624738: Binding constant for MLCK kinase domainkd0.0420uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.0980uM
N-[4-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]phenyl]pyrrolidine-2-carboxamide1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.0980uM
3-[4-[4-[2-[3-[(dimethylamino)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-1-ethylpyrazol-3-yl]phenyl]-1,1-dimethylurea1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.1040uM
N-[2-[4-[[4-(cyclobutylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-11-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-11-yl]-2-oxoethyl]acetamide1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.1090uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate624738: Binding constant for MLCK kinase domainkd0.1100uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one2198335: Inhibition of human MYLK3 using KKRPQRRYSNVF as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by radiometric Hot-SpotSM Kinase assayic500.1180uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.1290uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one624738: Binding constant for MLCK kinase domainkd0.1400uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide1526132: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MYLK3 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assaykd0.1460uM
6-bromo-3-(1-methylpyrazol-4-yl)-5-[(3R)-piperidin-3-yl]pyrazolo[1,5-a]pyrimidin-7-amine1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.1890uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2148811: Binding affinity to human MYLK3 incubated for 45 mins by Kinobead based pull down assaykd0.2849uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.3490uM
N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.3500uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol624738: Binding constant for MLCK kinase domainkd0.3600uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine624738: Binding constant for MLCK kinase domainkd0.4000uM
Quizartinib624738: Binding constant for MLCK kinase domainkd0.4100uM
3-[3-(2-piperidin-1-ylethoxy)phenyl]-5-(1H-1,2,4-triazol-5-yl)-1H-indazole1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd0.4830uM
8-(6-methoxy-3-pyridinyl)-3-methyl-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]imidazo[4,5-c]quinolin-2-one1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd1.1050uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide624738: Binding constant for MLCK kinase domainkd1.7000uM
Axitinib624738: Binding constant for MLCK kinase domainkd1.7000uM
Midostaurin624738: Binding constant for MLCK kinase domainkd2.3000uM
8-[2-methoxy-5-(4-methylpiperazin-1-yl)anilino]-1-methyl-4,5-dihydropyrazolo[4,5-h]quinazoline-3-carboxamide1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd2.9390uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide624738: Binding constant for MLCK kinase domainkd3.0000uM
3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide1425082: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.kd3.6470uM
Sorafenib624738: Binding constant for MLCK kinase domainkd9.6000uM
Fedratinib624738: Binding constant for MLCK kinase domainkd9.7000uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

ChemicalActions (top 5)PubMed papers
Benzo(a)pyreneaffects methylation, decreases expression, decreases methylation, increases mutagenesis4
bisphenol Adecreases methylation, increases expression3
Phenylmercuric Acetateaffects cotreatment, increases expression2
Valproic Acidaffects expression, increases expression2
Aflatoxin B1increases methylation, decreases expression2
aristolochic acid Iincreases expression1
Asian ginsengdecreases expression, decreases reaction1
hydroxyhydroquinonedecreases expression1
sulforaphanedecreases expression1
sodium arseniteaffects expression1
benzo(e)pyreneincreases methylation1
aflatoxin B2increases methylation1
cyanoginosin LRincreases expression, decreases methylation1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
abrineincreases expression1
dorsomorphinaffects cotreatment, increases expression1
theaflavin-3,3’-digallateaffects expression1
Resveratrolaffects cotreatment, decreases expression1
Copperaffects cotreatment, decreases expression1
Diazinonincreases methylation1
Diethylhexyl Phthalatedecreases expression, decreases reaction1
Estradiolincreases expression, affects binding1
Methapyrileneincreases methylation1
Triclosandecreases expression1
Asbestos, Serpentinedecreases methylation1
Asbestos, Crocidolitedecreases methylation1
Asbestos, Amositedecreases methylation1
Nanotubes, Carbondecreases expression1

ChEMBL screening assays

95 unique, capped per target: 95 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1908435BindingBinding constant for MLCK kinase domainComprehensive analysis of kinase inhibitor selectivity. — Nat Biotechnol

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

CellosaurusNameCategorySex
CVCL_E0IPUbigene HeLa MYLK3 KOCancer cell lineFemale
CVCL_SZ62HAP1 MYLK3 (-) 1Cancer cell lineMale
CVCL_SZ63HAP1 MYLK3 (-) 2Cancer cell lineMale
CVCL_SZ64HAP1 MYLK3 (-) 3Cancer cell lineMale
CVCL_SZ65HAP1 MYLK3 (-) 4Cancer cell lineMale

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT00374465PHASE4UNKNOWNTherapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903PHASE4COMPLETEDStudy of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140PHASE4COMPLETEDA Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149PHASE4COMPLETEDSupramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581PHASE4COMPLETEDCoenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022PHASE4RECRUITINGThe Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00333827PHASE3COMPLETEDCell Therapy In Dilated Cardiomyopathy
NCT00505154PHASE3COMPLETEDEffect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703PHASE3COMPLETEDPUFAs and Left Ventricular Function in Heart Failure
NCT01583114PHASE3TERMINATEDPREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081PHASE3UNKNOWNResveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181PHASE3UNKNOWNContinues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514PHASE3TERMINATEDA Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323PHASE3COMPLETEDMicophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766PHASE3COMPLETEDEffect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257PHASE3RECRUITINGBromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00629018PHASE2COMPLETEDSafety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096PHASE2COMPLETEDIntracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518PHASE2COMPLETEDUse of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964PHASE2COMPLETEDSafety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968PHASE2COMPLETEDUse of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171PHASE2COMPLETEDBone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310PHASE2COMPLETEDSafety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911PHASE2COMPLETEDA Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653PHASE2SUSPENDEDLeft Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660PHASE2ACTIVE_NOT_RECRUITINGUse of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM
NCT03775070PHASE2COMPLETEDSimvastatin Therapy in Patients With Dilated Cardiomyopathy.
NCT04405804PHASE2UNKNOWNEarly Administration of Ivabradine in Children With Heart Failure
NCT05410873PHASE2COMPLETEDExamining the Effects of Mitochondrial Oxidative Stress in DCM
NCT06632834PHASE2RECRUITINGOutcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
NCT00585546PHASE1TERMINATEDHarefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
NCT02293603PHASE1UNKNOWNDilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC)
NCT03062956PHASE1COMPLETEDA Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491
NCT03129568PHASE1COMPLETEDTranscoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy
NCT04982081PHASE1UNKNOWNTreating Congestive HF With hiPSC-CMs Through Endocardial Injection
NCT06381466PHASE1TERMINATEDA Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants.
NCT06464588PHASE1RECRUITINGA Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)
NCT06902896PHASE1COMPLETEDSafety and Efficacy of FAP iCDC in End-stage Dilated Cardiomyopathy
NCT07137338PHASE1RECRUITINGA Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy
NCT07241104PHASE1RECRUITINGA Study of AZD4063 in PLN R14del Dilated Cardiomyopathy