Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI2OREX)

• DOT Name: Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3)
• Synonyms: MAP kinase kinase 3; MAPKK 3; EC 2.7.12.2; MAPK/ERK kinase 3; MEK 3; Stress-activated protein kinase kinase 2; SAPK kinase 2; SAPKK-2; SAPKK2
• Gene Name: MAP2K3
• Related Disease:
  Glioma
  Lung adenocarcinoma
  Melanoma
  Adult glioblastoma
  Alzheimer disease
  Anthrax
  Bone osteosarcoma
  Breast neoplasm
  Carcinoma of esophagus
  Carcinoma of liver and intrahepatic biliary tract
  Cardiac failure
  Cerebral infarction
  Cervical cancer
  Cervical carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Esophageal cancer
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Liver cancer
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Metabolic disorder
  Myocardial ischemia
  Neoplasm
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Obesity
  Osteosarcoma
  Type-1/2 diabetes
  Advanced cancer
  Retinopathy
  Arthritis
  Asthma
  Breast cancer
  Breast carcinoma
• UniProt ID: MP2K3_HUMAN
• EC Number: 2.7.12.2
• Pfam ID: PF00069
• Sequence:
  MESPASSQPASMPQSKGKSKRKKDLRISCMSKPPAPNPTPPRNLDSRTFITIGDRNFEVE
  ADDLVTISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNSQEQKRLLMDLDINMRTVDC
  FYTVTFYGALFREGDVWICMELMDTSLDKFYRKVLDKNMTIPEDILGEIAVSIVRALEHL
  HSKLSVIHRDVKPSNVLINKEGHVKMCDFGISGYLVDSVAKTMDAGCKPYMAPERINPEL
  NQKGYNVKSDVWSLGITMIEMAILRFPYESWGTPFQQLKQVVEEPSPQLPADRFSPEFVD
  FTAQCLRKNPAERMSYLELMEHPFFTLHKTKKTDIAAFVKEILGEDS
• Function: Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14.
• Tissue Specificity: Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Rap1 sig.ling pathway (hsa04015)
  Cellular senescence (hsa04218)
  Toll-like receptor sig.ling pathway (hsa04620)
  Fc epsilon RI sig.ling pathway (hsa04664)
  TNF sig.ling pathway (hsa04668)
  Thermogenesis (hsa04714)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  GnRH sig.ling pathway (hsa04912)
  Growth hormone synthesis, secretion and action (hsa04935)
  Alcoholic liver disease (hsa04936)
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Salmonella infection (hsa05132)
  Yersinia infection (hsa05135)
  Toxoplasmosis (hsa05145)
  Hepatitis B (hsa05161)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  (Name not found)
  activated TAK1 mediates p38 MAPK activation (R-HSA-450302)
  Oxidative Stress Induced Senescence (R-HSA-2559580)

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Altered Expression	[1]
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[2]
Melanoma	DIS1RRCY	Definitive	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Anthrax	DISFPT78	Strong	Biomarker	[6]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[9]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[10]
Cardiac failure	DISDC067	Strong	Biomarker	[11]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[12]
Cervical cancer	DISFSHPF	Strong	Biomarker	[13]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[14]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[11]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
Liver cancer	DISDE4BI	Strong	Biomarker	[10]
Lung cancer	DISCM4YA	Strong	Biomarker	[16]
Lung carcinoma	DISTR26C	Strong	Biomarker	[16]
Lung neoplasm	DISVARNB	Strong	Biomarker	[17]
Metabolic disorder	DIS71G5H	Strong	Altered Expression	[18]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[21]
Obesity	DIS47Y1K	Strong	Altered Expression	[18]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[7]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[18]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[14]
Retinopathy	DISB4B0F	moderate	Therapeutic	[22]
Arthritis	DIST1YEL	Disputed	Biomarker	[23]
Asthma	DISW9QNS	Limited	Biomarker	[24]
Breast cancer	DIS7DPX1	Limited	Biomarker	[20]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[20]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3) increases the response to substance of Cisplatin.	[54]
Josamycin	DMKJ8LB	Approved	Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3) affects the response to substance of Josamycin.	[55]
Afimoxifene	DMFORDT	Phase 2	Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3) decreases the response to substance of Afimoxifene.	[56]

5 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 Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[25]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the phosphorylation of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[40]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the phosphorylation of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[42]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the phosphorylation of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[26]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[27]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[28]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the activity of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[29]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[31]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[32]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[33]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[34]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[35]
Selenium	DM25CGV	Approved	Selenium increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[36]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[37]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[38]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[34]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[39]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[41]
Daunorubicin	DMQUSBT	Approved	Daunorubicin increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[38]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[43]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[44]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[38]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[46]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[49]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[50]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[48]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[51]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl decreases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[52]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3).	[53]

References

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