Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZGF1Y5)

• DOT Name: Myocyte-specific enhancer factor 2C (MEF2C)
• Synonyms: Myocyte enhancer factor 2C
• Gene Name: MEF2C
• Related Disease:
  Colorectal carcinoma
  Complex neurodevelopmental disorder
  Intellectual disability, autosomal dominant 20
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Adenocarcinoma
  Advanced cancer
  Alcohol dependence
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Attention deficit hyperactivity disorder
  Cardiac failure
  Cataract
  Congestive heart failure
  Corpus callosum, agenesis of
  Dilated cardiomyopathy 1A
  Epilepsy
  Fanconi anemia complementation group A
  Fanconi's anemia
  Glioma
  Hepatocellular carcinoma
  Hypertrophic cardiomyopathy
  Intellectual disability
  Leukemia
  Mental disorder
  Myeloid leukaemia
  Myocardial infarction
  Parkinson disease
  Rett syndrome
  T-cell acute lymphoblastic leukaemia
  T-cell leukaemia
  Autism spectrum disorder
  Movement disorder
  Retinopathy
  Rhabdomyosarcoma
  Neoplasm
  Status epilepticus seizure
  Amyotrophic lateral sclerosis
  Autism
  Cardiomyopathy
  Congenital heart disease
  Dementia
  leukaemia
  Nervous system disease
  Neurodevelopmental disorder
  Non-insulin dependent diabetes
  Schizophrenia
• UniProt ID: MEF2C_HUMAN
• Pfam ID: PF12347 ; PF00319
• Sequence:
  MGRKKIQITRIMDERNRQVTFTKRKFGLMKKAYELSVLCDCEIALIIFNSTNKLFQYAST
  DMDKVLLKYTEYNEPHESRTNSDIVETLRKKGLNGCDSPDPDADDSVGHSPESEDKYRKI
  NEDIDLMISRQRLCAVPPPNFEMPVSIPVSSHNSLVYSNPVSSLGNPNLLPLAHPSLQRN
  SMSPGVTHRPPSAGNTGGLMGGDLTSGAGTSAGNGYGNPRNSPGLLVSPGNLNKNMQAKS
  PPPMNLGMNNRKPDLRVLIPPGSKNTMPSVSEDVDLLLNQRINNSQSAQSLATPVVSVAT
  PTLPGQGMGGYPSAISTTYGTEYSLSSADLSSLSGFNTASALHLGSVTGWQQQHLHNMPP
  SALSQLGACTSTHLSQSSNLSLPSTQSLNIKSEPVSPPRDRTTTPSRYPQHTRHEAGRSP
  VDSLSSCSSSYDGSDREDHRNEFHSPIGLTRPSPDERESPSVKRMRLSEGWAT
• Function: Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes. Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development. Enhances transcriptional activation mediated by SOX18. Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. Necessary for proper development of megakaryocytes and platelets and for bone marrow B-lymphopoiesis. Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B-cells. May also be involved in neurogenesis and in the development of cortical architecture. Isoforms that lack the repressor domain are more active than isoform 1.
• Tissue Specificity: Expressed in brain and skeletal muscle.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  cGMP-PKG sig.ling pathway (hsa04022)
  Apelin sig.ling pathway (hsa04371)
  Oxytocin sig.ling pathway (hsa04921)
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  Transcriptio.l misregulation in cancer (hsa05202)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)
  Circadian Clock (R-HSA-400253)
  Myogenesis (R-HSA-525793)
  MECP2 regulates transcription factors (R-HSA-9022707)
  Heme signaling (R-HSA-9707616)
  Cardiogenesis (R-HSA-9733709)
  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
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Complex neurodevelopmental disorder	DISB9AFI	Definitive	Autosomal dominant	[2]
Intellectual disability, autosomal dominant 20	DISFYTEE	Definitive	Autosomal dominant	[3]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[4]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[5]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[6]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[7]
Alcohol dependence	DIS4ZSCO	Strong	Genetic Variation	[8]
Alzheimer disease	DISF8S70	Strong	Biomarker	[9]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[10]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[10]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[11]
Cardiac failure	DISDC067	Strong	Altered Expression	[12]
Cataract	DISUD7SL	Strong	Biomarker	[13]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[12]
Corpus callosum, agenesis of	DISO9P40	Strong	Genetic Variation	[14]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[15]
Epilepsy	DISBB28L	Strong	Biomarker	[16]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Altered Expression	[17]
Fanconi's anemia	DISGW6Q8	Strong	Altered Expression	[17]
Glioma	DIS5RPEH	Strong	Biomarker	[18]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[19]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Altered Expression	[20]
Intellectual disability	DISMBNXP	Strong	Biomarker	[21]
Leukemia	DISNAKFL	Strong	Biomarker	[22]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[23]
Myeloid leukaemia	DISMN944	Strong	Altered Expression	[24]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[25]
Parkinson disease	DISQVHKL	Strong	Biomarker	[26]
Rett syndrome	DISGG5UV	Strong	Genetic Variation	[27]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Altered Expression	[28]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[29]
Autism spectrum disorder	DISXK8NV	moderate	CausalMutation	[30]
Movement disorder	DISOJJ2D	moderate	CausalMutation	[31]
Retinopathy	DISB4B0F	moderate	Biomarker	[32]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[33]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[34]
Status epilepticus seizure	DISY3BIC	Disputed	Biomarker	[35]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[36]
Autism	DISV4V1Z	Limited	Biomarker	[21]
Cardiomyopathy	DISUPZRG	Limited	Altered Expression	[37]
Congenital heart disease	DISQBA23	Limited	Altered Expression	[38]
Dementia	DISXL1WY	Limited	Altered Expression	[39]
leukaemia	DISS7D1V	Limited	Biomarker	[22]
Nervous system disease	DISJ7GGT	Limited	Altered Expression	[39]
Neurodevelopmental disorder	DIS372XH	Limited	Altered Expression	[40]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[41]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[42]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Myocyte-specific enhancer factor 2C (MEF2C) increases the Metabolic disorder ADR of Chlorothiazide.	[65]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[43]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[44]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[45]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[46]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[47]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[48]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[50]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[51]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[52]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[53]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[51]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[54]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[55]
Rofecoxib	DM3P5DA	Approved	Rofecoxib affects the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[56]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[57]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[58]
Acadesine	DM1RMF5	Phase 3	Acadesine decreases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[59]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[60]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[57]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[63]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Myocyte-specific enhancer factor 2C (MEF2C).	[64]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Myocyte-specific enhancer factor 2C (MEF2C).	[49]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Myocyte-specific enhancer factor 2C (MEF2C).	[61]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Myocyte-specific enhancer factor 2C (MEF2C).	[62]

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