Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6WAO12)

• DOT Name: Dual specificity protein phosphatase 4 (DUSP4)
• Synonyms: EC 3.1.3.16; EC 3.1.3.48; Dual specificity protein phosphatase hVH2; Mitogen-activated protein kinase phosphatase 2; MAP kinase phosphatase 2; MKP-2
• Gene Name: DUSP4
• Related Disease:
  Diabetic kidney disease
  Leishmaniasis
  Megalencephalic leukoencephalopathy with subcortical cysts
  Ovarian neoplasm
  Type-1/2 diabetes
  Visceral leishmaniasis
  Anal intraepithelial neoplasia
  Anaplastic astrocytoma
  B-cell lymphoma
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cardiomyopathy
  Colorectal carcinoma
  Craniosynostosis
  Depression
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Head-neck squamous cell carcinoma
  Juvenile idiopathic arthritis
  Lung adenocarcinoma
  Lupus
  Marinesco-Sjogren syndrome
  Melanoma
  Neoplasm
  Non-small-cell lung cancer
  Pancreatic tumour
  Stomach cancer
  Systemic lupus erythematosus
  Advanced cancer
  Metastatic malignant neoplasm
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Hepatocellular carcinoma
  Ankylosing spondylitis
  Lung cancer
  Lung carcinoma
  Renal fibrosis
  Triple negative breast cancer
• UniProt ID: DUS4_HUMAN
• PDB ID: 3EZZ
• EC Number: 3.1.3.16; 3.1.3.48
• Pfam ID: PF00782 ; PF00581
• Sequence:
  MVTMEELREMDCSVLKRLMNRDENGGGAGGSGSHGTLGLPSGGKCLLLDCRPFLAHSAGY
  ILGSVNVRCNTIVRRRAKGSVSLEQILPAEEEVRARLRSGLYSAVIVYDERSPRAESLRE
  DSTVSLVVQALRRNAERTDICLLKGGYERFSSEYPEFCSKTKALAAIPPPVPPSATEPLD
  LGCSSCGTPLHDQGGPVEILPFLYLGSAYHAARRDMLDALGITALLNVSSDCPNHFEGHY
  QYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYLMMKKR
  VRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLATSCAAEAASPSGPLRERGKTPATP
  TSQFVFSFPVSVGVHSAPSSLPYLHSPITTSPSC
• Function: Regulates mitogenic signal transduction by dephosphorylating both Thr and Tyr residues on MAP kinases ERK1 and ERK2.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Efferocytosis (hsa04148)
• Reactome Pathway:
  ERKs are inactivated (R-HSA-202670)
  Negative regulation of MAPK pathway (R-HSA-5675221)
  RAF-independent MAPK1/3 activation (R-HSA-112409)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic kidney disease	DISJMWEY	Definitive	Altered Expression	[1]
Leishmaniasis	DISABTW7	Definitive	Biomarker	[2]
Megalencephalic leukoencephalopathy with subcortical cysts	DISK9A1M	Definitive	Altered Expression	[2]
Ovarian neoplasm	DISEAFTY	Definitive	Altered Expression	[3]
Type-1/2 diabetes	DISIUHAP	Definitive	Altered Expression	[1]
Visceral leishmaniasis	DISTKEYK	Definitive	Biomarker	[2]
Anal intraepithelial neoplasia	DISJ0JW3	Strong	Biomarker	[4]
Anaplastic astrocytoma	DISSBE0K	Strong	Posttranslational Modification	[5]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[6]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Carcinoma	DISH9F1N	Strong	Biomarker	[4]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[10]
Craniosynostosis	DIS6J405	Strong	Biomarker	[11]
Depression	DIS3XJ69	Strong	Biomarker	[12]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[13]
Glioblastoma multiforme	DISK8246	Strong	Posttranslational Modification	[5]
Glioma	DIS5RPEH	Strong	Biomarker	[14]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[15]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[16]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[17]
Lupus	DISOKJWA	Strong	Biomarker	[18]
Marinesco-Sjogren syndrome	DISKEU0B	Strong	Altered Expression	[19]
Melanoma	DIS1RRCY	Strong	Biomarker	[20]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[22]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[4]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[13]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[18]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[23]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[13]
Thyroid cancer	DIS3VLDH	moderate	Biomarker	[24]
Thyroid gland carcinoma	DISMNGZ0	moderate	Biomarker	[24]
Thyroid tumor	DISLVKMD	moderate	Biomarker	[24]
Hepatocellular carcinoma	DIS0J828	Disputed	Altered Expression	[25]
Ankylosing spondylitis	DISRC6IR	Limited	Altered Expression	[26]
Lung cancer	DISCM4YA	Limited	Biomarker	[17]
Lung carcinoma	DISTR26C	Limited	Biomarker	[17]
Renal fibrosis	DISMHI3I	Limited	Altered Expression	[27]
Triple negative breast cancer	DISAMG6N	Limited	Altered Expression	[28]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Dual specificity protein phosphatase 4 (DUSP4) affects the response to substance of Methotrexate.	[66]
Mitomycin	DMH0ZJE	Approved	Dual specificity protein phosphatase 4 (DUSP4) affects the response to substance of Mitomycin.	[66]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Dual specificity protein phosphatase 4 (DUSP4).	[29]

40 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 protein phosphatase 4 (DUSP4).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[33]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[34]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[35]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[36]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[37]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[38]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[39]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[40]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[41]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[42]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[43]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[44]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[45]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[46]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[47]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[33]
Daunorubicin	DMQUSBT	Approved	Daunorubicin increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[33]
Febuxostat	DMDEXQ0	Approved	Febuxostat increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[48]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[49]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[50]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[37]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[51]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[52]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[53]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[54]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[55]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[56]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[57]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[58]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[59]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[60]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[61]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[62]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[63]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[64]
Glyphosate	DM0AFY7	Investigative	Glyphosate affects the expression of Dual specificity protein phosphatase 4 (DUSP4).	[65]
Daidzein	DMRFTJX	Investigative	Daidzein decreases the expression of Dual specificity protein phosphatase 4 (DUSP4).	[53]

References

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