Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4FU8C0)

• DOT Name: Nuclear protein 1 (NUPR1)
• Synonyms: Candidate of metastasis 1; Protein p8
• Gene Name: NUPR1
• Related Disease:
  Bone osteosarcoma
  Osteosarcoma
  Pancreatic cancer
  Advanced cancer
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma of liver and intrahepatic biliary tract
  Endometrial cancer
  Endometrial carcinoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Leprosy
  Liver cancer
  Neoplasm
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Obesity
  Pancreatic adenocarcinoma
  Prostate neoplasm
  Synovial sarcoma
  Thyroid gland follicular carcinoma
  Thyroid tumor
  Undifferentiated carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  B-cell neoplasm
  High blood pressure
  Plasma cell myeloma
  Adult glioblastoma
  Colorectal carcinoma
  Lysosomal lipid storage disorder
  Matthew-Wood syndrome
  Metastatic malignant neoplasm
  Osteoarthritis
  Pancreatic ductal carcinoma
  Pancreatitis
  Prostate cancer
  Prostate carcinoma
  Q fever
  Squamous cell carcinoma
• UniProt ID: NUPR1_HUMAN
• Pfam ID: PF10195
• Sequence:
  MATFPPATSAPQQPPGPEDEDSSLDESDLYSLAHSYLGGGGRKGRTKREAAANTNRPSPG
  GHERKLVTKLQNSERKKRGARR
• Function: Transcription regulator that converts stress signals into a program of gene expression that empowers cells with resistance to the stress induced by a change in their microenvironment. Thereby participates in regulation of many process namely cell-cycle, apoptosis, autophagy and DNA repair responses. Controls cell cycle progression and protects cells from genotoxic stress induced by doxorubicin through the complex formation with TP53 and EP300 that binds CDKN1A promoter leading to transcriptional induction of CDKN1A. Protects pancreatic cancer cells from stress-induced cell death by binding the RELB promoter and activating its transcription, leading to IER3 transactivation. Negatively regulates apoptosis through interaction with PTMA. Inhibits autophagy-induced apoptosis in cardiac cells through FOXO3 interaction, inducing cytoplasmic translocation of FOXO3 thereby preventing the FOXO3 association with the pro-autophagic BNIP3 promoter. Inhibits cell growth and facilitates programmed cell death by apoptosis after adriamycin-induced DNA damage through transactivation of TP53. Regulates methamphetamine-induced apoptosis and autophagy through DDIT3-mediated endoplasmic reticulum stress pathway. Participates in DNA repair following gamma-irradiation by facilitating DNA access of the transcription machinery through interaction with MSL1 leading to inhibition of histone H4' Lys-16' acetylation (H4K16ac). Coactivator of PAX2 transcription factor activity, both by recruiting EP300 to increase PAX2 transcription factor activity and by binding PAXIP1 to suppress PAXIP1-induced inhibition on PAX2. Positively regulates cell cycle progression through interaction with COPS5 inducing cytoplasmic translocation of CDKN1B leading to the CDKN1B degradation. Coordinates, through its interaction with EP300, the assiociation of MYOD1, EP300 and DDX5 to the MYOG promoter, leading to inhibition of cell-cycle progression and myogenic differentiation promotion. Negatively regulates beta cell proliferation via inhibition of cell-cycle regulatory genes expression through the suppression of their promoter activities. Also required for LHB expression and ovarian maturation. Exacerbates CNS inflammation and demyelination upon cuprizone treatment.
• Tissue Specificity: Widely expressed, with high levels in liver, pancreas, prostate, ovary, colon, thyroid, spinal cord, trachea and adrenal gland, moderate levels in heart, placenta, lung, skeletal muscle, kidney, testis, small intestine, stomach and lymph node, and low levels in brain, spleen, thymus and bone marrow. Not detected in peripheral blood leukocytes.
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Altered Expression	[1]
Osteosarcoma	DISLQ7E2	Definitive	Altered Expression	[1]
Pancreatic cancer	DISJC981	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[7]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[8]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[8]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Leprosy	DISAA4UI	Strong	Biomarker	[11]
Liver cancer	DISDE4BI	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[12]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[14]
Obesity	DIS47Y1K	Strong	Genetic Variation	[13]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Biomarker	[15]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[16]
Synovial sarcoma	DISEZJS7	Strong	Altered Expression	[17]
Thyroid gland follicular carcinoma	DISFK2QT	Strong	Biomarker	[18]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[18]
Undifferentiated carcinoma	DISIAZST	Strong	Biomarker	[18]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[4]
B-cell neoplasm	DISVY326	moderate	Altered Expression	[19]
High blood pressure	DISY2OHH	moderate	Altered Expression	[20]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[19]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[21]
Lysosomal lipid storage disorder	DISXQRTX	Limited	Biomarker	[22]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[23]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[24]
Osteoarthritis	DIS05URM	Limited	Biomarker	[25]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[23]
Pancreatitis	DIS0IJEF	Limited	Altered Expression	[26]
Prostate cancer	DISF190Y	Limited	Biomarker	[14]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[16]
Q fever	DISK1S90	Limited	Biomarker	[27]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Nuclear protein 1 (NUPR1) affects the response to substance of Etoposide.	[56]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
D-glucose	DMMG2TO	Investigative	Nuclear protein 1 (NUPR1) decreases the abundance of D-glucose.	[57]

2 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 Nuclear protein 1 (NUPR1).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Nuclear protein 1 (NUPR1).	[50]

49 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 Nuclear protein 1 (NUPR1).	[29]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Nuclear protein 1 (NUPR1).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Nuclear protein 1 (NUPR1).	[31]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nuclear protein 1 (NUPR1).	[32]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Nuclear protein 1 (NUPR1).	[33]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Nuclear protein 1 (NUPR1).	[34]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Nuclear protein 1 (NUPR1).	[35]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Nuclear protein 1 (NUPR1).	[22]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Nuclear protein 1 (NUPR1).	[37]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Nuclear protein 1 (NUPR1).	[38]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Nuclear protein 1 (NUPR1).	[39]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Nuclear protein 1 (NUPR1).	[40]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Nuclear protein 1 (NUPR1).	[41]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Nuclear protein 1 (NUPR1).	[42]
Haloperidol	DM96SE0	Approved	Haloperidol increases the expression of Nuclear protein 1 (NUPR1).	[22]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Nuclear protein 1 (NUPR1).	[40]
Sertraline	DM0FB1J	Approved	Sertraline increases the expression of Nuclear protein 1 (NUPR1).	[40]
Isoniazid	DM5JVS3	Approved	Isoniazid increases the expression of Nuclear protein 1 (NUPR1).	[22]
Tetracycline	DMZA017	Approved	Tetracycline increases the expression of Nuclear protein 1 (NUPR1).	[22]
Thioridazine	DM35M8J	Approved	Thioridazine increases the expression of Nuclear protein 1 (NUPR1).	[40]
Imipramine	DM2NUH3	Approved	Imipramine increases the expression of Nuclear protein 1 (NUPR1).	[40]
Clomipramine	DMINRKW	Approved	Clomipramine increases the expression of Nuclear protein 1 (NUPR1).	[40]
Citalopram	DM2G9AE	Approved	Citalopram increases the expression of Nuclear protein 1 (NUPR1).	[43]
Erythromycin	DM4K7GQ	Approved	Erythromycin decreases the expression of Nuclear protein 1 (NUPR1).	[22]
Loratadine	DMF3AN7	Approved	Loratadine increases the expression of Nuclear protein 1 (NUPR1).	[40]
Pentamidine	DMHZJCG	Approved	Pentamidine increases the expression of Nuclear protein 1 (NUPR1).	[40]
Quinidine	DMLPICK	Approved	Quinidine increases the expression of Nuclear protein 1 (NUPR1).	[43]
Flecainide	DMSQDLE	Approved	Flecainide increases the expression of Nuclear protein 1 (NUPR1).	[40]
Perhexiline	DMINO7Z	Approved	Perhexiline increases the expression of Nuclear protein 1 (NUPR1).	[22]
Ofloxacin	DM0VQN3	Approved	Ofloxacin increases the expression of Nuclear protein 1 (NUPR1).	[22]
Doxepin	DMPI98T	Approved	Doxepin increases the expression of Nuclear protein 1 (NUPR1).	[43]
Fenretinide	DMRD5SP	Phase 3	Fenretinide affects the expression of Nuclear protein 1 (NUPR1).	[39]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine increases the expression of Nuclear protein 1 (NUPR1).	[40]
Dexanabinol	DMRH291	Phase 3	Dexanabinol increases the expression of Nuclear protein 1 (NUPR1).	[44]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Nuclear protein 1 (NUPR1).	[40]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Nuclear protein 1 (NUPR1).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nuclear protein 1 (NUPR1).	[46]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Nuclear protein 1 (NUPR1).	[47]
Chlorcyclizine	DM3L52Q	Phase 1	Chlorcyclizine increases the expression of Nuclear protein 1 (NUPR1).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Nuclear protein 1 (NUPR1).	[48]
ZIMELIDINE	DMNI3U2	Withdrawn from market	ZIMELIDINE increases the expression of Nuclear protein 1 (NUPR1).	[40]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Nuclear protein 1 (NUPR1).	[39]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Nuclear protein 1 (NUPR1).	[49]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Nuclear protein 1 (NUPR1).	[51]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Nuclear protein 1 (NUPR1).	[52]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Nuclear protein 1 (NUPR1).	[53]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Nuclear protein 1 (NUPR1).	[33]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Nuclear protein 1 (NUPR1).	[54]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Nuclear protein 1 (NUPR1).	[55]

References

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