Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2363Z9)

• DOT Name: Tumor protein p53-inducible nuclear protein 1 (TP53INP1)
• Synonyms: Stress-induced protein; p53-dependent damage-inducible nuclear protein 1; p53DINP1
• Gene Name: TP53INP1
• Related Disease:
  Ependymoma
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Alzheimer disease
  Anaplastic large cell lymphoma
  Anxiety
  Anxiety disorder
  B-cell neoplasm
  Bone osteosarcoma
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Depression
  Gastric cancer
  Gastric neoplasm
  Glioma
  Hepatocellular carcinoma
  Mantle cell lymphoma
  Metastatic malignant neoplasm
  Neuroblastoma
  Non-insulin dependent diabetes
  Osteosarcoma
  Renal cell carcinoma
  Stomach cancer
  Type-1/2 diabetes
  Varicose veins
  Colorectal carcinoma
  Gastritis
  Major depressive disorder
  Melanoma
  Breast cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Dermatomyositis
  Generalized anxiety disorder
  Liver cancer
  Neoplasm
  Small lymphocytic lymphoma
  Stroke
• UniProt ID: T53I1_HUMAN
• Pfam ID: PF14839
• Sequence:
  MFQRLNKMFVGEVSSSSNQEPEFNEKEDDEWILVDFIDTCTGFSAEEEEEEEDISEESPT
  EHPSVFSCLPASLECLADTSDSCFLQFESCPMEESWFITPPPCFTAGGLTTIKVETSPME
  NLLIEHPSMSVYAVHNSCPGLSEATRGTDELHSPSSPRVEAQNEMGQHIHCYVAALAAHT
  TFLEQPKSFRPSQWIKEHSERQPLNRNSLRRQNLTRDCHPRQVKHNGWVVHQPCPRQYNY
• Function: Antiproliferative and proapoptotic protein involved in cell stress response which acts as a dual regulator of transcription and autophagy. Acts as a positive regulator of autophagy. In response to cellular stress or activation of autophagy, relocates to autophagosomes where it interacts with autophagosome-associated proteins GABARAP, GABARAPL1/L2, MAP1LC3A/B/C and regulates autophagy. Acts as an antioxidant and plays a major role in p53/TP53-driven oxidative stress response. Possesses both a p53/TP53-independent intracellular reactive oxygen species (ROS) regulatory function and a p53/TP53-dependent transcription regulatory function. Positively regulates p53/TP53 and p73/TP73 and stimulates their capacity to induce apoptosis and regulate cell cycle. In response to double-strand DNA breaks, promotes p53/TP53 phosphorylation on 'Ser-46' and subsequent apoptosis. Acts as a tumor suppressor by inducing cell death by an autophagy and caspase-dependent mechanism. Can reduce cell migration by regulating the expression of SPARC.
• Tissue Specificity: Ubiquitously expressed.
• Reactome Pathway:
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  TP53 Regulates Transcription of Genes Involved in Cytochrome C Release (R-HSA-6803204)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ependymoma	DISUMRNZ	Definitive	Biomarker	[1]
Pancreatic cancer	DISJC981	Definitive	Biomarker	[2]
Prostate cancer	DISF190Y	Definitive	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Anaplastic large cell lymphoma	DISP4D1R	Strong	Altered Expression	[5]
Anxiety	DISIJDBA	Strong	Biomarker	[6]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[6]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[7]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[8]
Cervical cancer	DISFSHPF	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[10]
Colon cancer	DISVC52G	Strong	Genetic Variation	[11]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[11]
Depression	DIS3XJ69	Strong	Biomarker	[6]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[12]
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[13]
Glioma	DIS5RPEH	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
Mantle cell lymphoma	DISFREOV	Strong	Biomarker	[16]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[17]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[18]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[19]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[8]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[10]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[12]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[20]
Varicose veins	DISIMBN2	Strong	Biomarker	[21]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[22]
Gastritis	DIS8G07K	moderate	Altered Expression	[13]
Major depressive disorder	DIS4CL3X	moderate	Genetic Variation	[23]
Melanoma	DIS1RRCY	moderate	Biomarker	[24]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[25]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[25]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[26]
Dermatomyositis	DIS50C5O	Limited	Biomarker	[27]
Generalized anxiety disorder	DISPSQCW	Limited	Genetic Variation	[23]
Liver cancer	DISDE4BI	Limited	Biomarker	[26]
Neoplasm	DISZKGEW	Limited	Altered Expression	[7]
Small lymphocytic lymphoma	DIS30POX	Limited	Altered Expression	[28]
Stroke	DISX6UHX	Limited	Biomarker	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[34]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[35]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[36]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[38]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide affects the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[39]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[40]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[41]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[42]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[43]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[44]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[45]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[46]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[47]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[48]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[49]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[50]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[47]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[51]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[47]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[47]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[47]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[47]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[52]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[47]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[53]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[54]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[55]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[57]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[59]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[60]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[45]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[61]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[62]
I-BET151	DMYRUH2	Investigative	I-BET151 increases the expression of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[63]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[56]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Tumor protein p53-inducible nuclear protein 1 (TP53INP1).	[58]

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