Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV2SF6E)

• DOT Name: Myocyte-specific enhancer factor 2A (MEF2A)
• Synonyms: Serum response factor-like protein 1
• Gene Name: MEF2A
• Related Disease:
  Epilepsy
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Autism
  Autism spectrum disorder
  Carcinoma
  Cardiomyopathy
  Cardiovascular disease
  Classic Hodgkin lymphoma
  Colorectal carcinoma
  Depression
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  High blood pressure
  Hypertrophic cardiomyopathy
  Liver cirrhosis
  Malignant soft tissue neoplasm
  Medulloblastoma
  Myocardial ischemia
  Neoplasm
  Neuralgia
  Non-insulin dependent diabetes
  Ovarian cancer
  Ovarian neoplasm
  Polycystic ovarian syndrome
  Psychotic disorder
  Sarcoma
  Schizophrenia
  Systemic lupus erythematosus
  Cardiac failure
  Congestive heart failure
  Pancreatic cancer
  Advanced cancer
  Amyotrophic lateral sclerosis
  Arrhythmia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Castration-resistant prostate carcinoma
  Congenital diaphragmatic hernia
  Mental disorder
  Nervous system disease
  Neurodevelopmental disorder
  Type-1 diabetes
  Type-1/2 diabetes
• UniProt ID: MEF2A_HUMAN
• PDB ID: 1C7U; 1EGW; 1LEW; 3KOV; 3MU6; 3P57; 6BYY; 6BZ1
• Pfam ID: PF12347 ; PF00319
• Sequence:
  MGRKKIQITRIMDERNRQVTFTKRKFGLMKKAYELSVLCDCEIALIIFNSSNKLFQYAST
  DMDKVLLKYTEYNEPHESRTNSDIVEALNKKEHRGCDSPDPDTSYVLTPHTEEKYKKINE
  EFDNMMRNHKIAPGLPPQNFSMSVTVPVTSPNALSYTNPGSSLVSPSLAASSTLTDSSML
  SPPQTTLHRNVSPGAPQRPPSTGNAGGMLSTTDLTVPNGAGSSPVGNGFVNSRASPNLIG
  ATGANSLGKVMPTKSPPPPGGGNLGMNSRKPDLRVVIPPSSKGMMPPLSEEEELELNTQR
  ISSSQATQPLATPVVSVTTPSLPPQGLVYSAMPTAYNTDYSLTSADLSALQGFNSPGMLS
  LGQVSAWQQHHLGQAALSSLVAGGQLSQGSNLSINTNQNISIKSEPISPPRDRMTPSGFQ
  QQQQQQQQQQPPPPPQPQPQPPQPQPRQEMGRSPVDSLSSSSSSYDGSDREDPRGDFHSP
  IVLGRPPNTEDRESPSVKRMRMDAWVT
• Function: Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation. Associates with chromatin to the ZNF16 promoter.
• Tissue Specificity: Isoform MEF2 and isoform MEFA are expressed only in skeletal and cardiac muscle and in the brain. Isoform RSRFC4 and isoform RSRFC9 are expressed in all tissues examined.
• KEGG Pathway:
  cGMP-PKG sig.ling pathway (hsa04022)
  Apelin sig.ling pathway (hsa04371)
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Myogenesis (R-HSA-525793)
  ERK/MAPK targets (R-HSA-198753)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epilepsy	DISBB28L	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[3]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[3]
Autism	DISV4V1Z	Strong	Biomarker	[4]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[6]
Cardiomyopathy	DISUPZRG	Strong	Altered Expression	[7]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[8]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[10]
Depression	DIS3XJ69	Strong	Biomarker	[11]
Dilated cardiomyopathy	DISX608J	Strong	Altered Expression	[12]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[13]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
High blood pressure	DISY2OHH	Strong	Biomarker	[15]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Biomarker	[13]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[16]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[17]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[18]
Myocardial ischemia	DISFTVXF	Strong	Genetic Variation	[19]
Neoplasm	DISZKGEW	Strong	Altered Expression	[20]
Neuralgia	DISWO58J	Strong	Biomarker	[21]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[22]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[6]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[6]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[23]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[24]
Sarcoma	DISZDG3U	Strong	Biomarker	[25]
Schizophrenia	DISSRV2N	Strong	Biomarker	[4]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[26]
Cardiac failure	DISDC067	moderate	Biomarker	[27]
Congestive heart failure	DIS32MEA	moderate	Biomarker	[27]
Pancreatic cancer	DISJC981	moderate	Genetic Variation	[28]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[29]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[30]
Arrhythmia	DISFF2NI	Limited	Altered Expression	[31]
Breast cancer	DIS7DPX1	Limited	Biomarker	[32]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[32]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[32]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Genetic Variation	[33]
Congenital diaphragmatic hernia	DIS0IPVU	Limited	Genetic Variation	[34]
Mental disorder	DIS3J5R8	Limited	Biomarker	[4]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[35]
Neurodevelopmental disorder	DIS372XH	Limited	Biomarker	[4]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[36]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[36]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Myocyte-specific enhancer factor 2A (MEF2A).	[37]
TAK-243	DM4GKV2	Phase 1	TAK-243 affects the sumoylation of Myocyte-specific enhancer factor 2A (MEF2A).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Myocyte-specific enhancer factor 2A (MEF2A).	[50]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[40]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[41]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[42]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[42]
Glucosamine	DM4ZLFD	Approved	Glucosamine decreases the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[43]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[44]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[45]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[46]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[48]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[49]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[51]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Myocyte-specific enhancer factor 2A (MEF2A).	[52]

References

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