Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI8YKKE)

• DOT Name: DNA damage-inducible transcript 3 protein (DDIT3)
• Synonyms: DDIT-3; C/EBP zeta; C/EBP-homologous protein; CHOP; C/EBP-homologous protein 10; CHOP-10; CCAAT/enhancer-binding protein homologous protein; Growth arrest and DNA damage-inducible protein GADD153
• Gene Name: DDIT3
• Related Disease:
  Acute kidney injury
  Intestinal disorder
  Pleomorphic sarcoma
  Ulcer
  Acute myelogenous leukaemia
  Adult lymphoma
  Advanced cancer
  Alzheimer disease
  Asbestosis
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Chronic obstructive pulmonary disease
  Colorectal carcinoma
  Ewing sarcoma
  Fatty liver disease
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Juvenile idiopathic arthritis
  Lung cancer
  Lung carcinoma
  Lymphoma
  Malignant soft tissue neoplasm
  Myocardial infarction
  Neuroblastoma
  Non-insulin dependent diabetes
  Obesity
  Ocular hypertension
  Pediatric lymphoma
  Prostate cancer
  Prostate carcinoma
  Pulmonary fibrosis
  Sarcoma
  Type-1/2 diabetes
  B-cell lymphoma
  Follicular lymphoma
  B-cell neoplasm
  Colon cancer
  Colon carcinoma
  Contact dermatitis
  Galactosemia
  Gastric cancer
  Melanoma
  Stomach cancer
  Type-1 diabetes
• UniProt ID: DDIT3_HUMAN
• Sequence:
  MAAESLPFSFGTLSSWELEAWYEDLQEVLSSDENGGTYVSPPGNEEEESKIFTTLDPASL
  AWLTEEEPEPAEVTSTSQSPHSPDSSQSSLAQEEEEEDQGRTRKRKQSGHSPARAGKQRM
  KEKEQENERKVAQLAEENERLKQEIERLTREVEATRRALIDRMVNLHQA
• Function: Multifunctional transcription factor in endoplasmic reticulum (ER) stress response. Plays an essential role in the response to a wide variety of cell stresses and induces cell cycle arrest and apoptosis in response to ER stress. Plays a dual role both as an inhibitor of CCAAT/enhancer-binding protein (C/EBP) function and as an activator of other genes. Acts as a dominant-negative regulator of C/EBP-induced transcription: dimerizes with members of the C/EBP family, impairs their association with C/EBP binding sites in the promoter regions, and inhibits the expression of C/EBP regulated genes. Positively regulates the transcription of TRIB3, IL6, IL8, IL23, TNFRSF10B/DR5, PPP1R15A/GADD34, BBC3/PUMA, BCL2L11/BIM and ERO1L. Negatively regulates; expression of BCL2 and MYOD1, ATF4-dependent transcriptional activation of asparagine synthetase (ASNS), CEBPA-dependent transcriptional activation of hepcidin (HAMP) and CEBPB-mediated expression of peroxisome proliferator-activated receptor gamma (PPARG). Together with ATF4, mediates ER-mediated cell death by promoting expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the unfolded protein response (UPR) in response to ER stress. Inhibits the canonical Wnt signaling pathway by binding to TCF7L2/TCF4, impairing its DNA-binding properties and repressing its transcriptional activity. Plays a regulatory role in the inflammatory response through the induction of caspase-11 (CASP4/CASP11) which induces the activation of caspase-1 (CASP1) and both these caspases increase the activation of pro-IL1B to mature IL1B which is involved in the inflammatory response. Acts as a major regulator of postnatal neovascularization through regulation of endothelial nitric oxide synthase (NOS3)-related signaling.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Protein processing in endoplasmic reticulum (hsa04141)
  Apoptosis (hsa04210)
  Non-alcoholic fatty liver disease (hsa04932)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Transcriptio.l misregulation in cancer (hsa05202)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  ATF6 (ATF6-alpha) activates chaperone genes (R-HSA-381183)
  FOXO-mediated transcription of cell death genes (R-HSA-9614657)
  Response of EIF2AK4 (GCN2) to amino acid deficiency (R-HSA-9633012)
  Response of EIF2AK1 (HRI) to heme deficiency (R-HSA-9648895)
  ATF4 activates genes in response to endoplasmic reticulum stress (R-HSA-380994)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute kidney injury	DISXZG0T	Definitive	Biomarker	[1]
Intestinal disorder	DISGPMUQ	Definitive	Biomarker	[2]
Pleomorphic sarcoma	DISXU8CC	Definitive	Genetic Variation	[3]
Ulcer	DISHF2X6	Definitive	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Asbestosis	DISO5XCZ	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[10]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Therapeutic	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[12]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[13]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[16]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[17]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[18]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[5]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[19]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[20]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[21]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[22]
Obesity	DIS47Y1K	Strong	Biomarker	[23]
Ocular hypertension	DISC2BT9	Strong	Therapeutic	[24]
Pediatric lymphoma	DIS51BK2	Strong	Genetic Variation	[5]
Prostate cancer	DISF190Y	Strong	Altered Expression	[25]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[25]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[26]
Sarcoma	DISZDG3U	Strong	Biomarker	[19]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[27]
B-cell lymphoma	DISIH1YQ	moderate	Biomarker	[28]
Follicular lymphoma	DISVEUR6	Disputed	Biomarker	[29]
B-cell neoplasm	DISVY326	Limited	Genetic Variation	[30]
Colon cancer	DISVC52G	Limited	Biomarker	[31]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[31]
Contact dermatitis	DISQ3AU0	Limited	Biomarker	[32]
Galactosemia	DIS6V2Q3	Limited	Biomarker	[33]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[34]
Melanoma	DIS1RRCY	Limited	Biomarker	[35]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[34]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[36]

100 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 DNA damage-inducible transcript 3 protein (DDIT3).	[37]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[41]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[43]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[44]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[45]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[46]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[47]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[48]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[49]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[39]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[50]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[51]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[52]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[53]
Marinol	DM70IK5	Approved	Marinol decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[54]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[55]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[56]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[57]
Menadione	DMSJDTY	Approved	Menadione increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[49]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[58]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[59]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[60]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[16]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[62]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[63]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[64]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[65]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[66]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[67]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[68]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[69]
Aspirin	DM672AH	Approved	Aspirin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[70]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[71]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[51]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[72]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[73]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[74]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[75]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[67]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[67]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[76]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[77]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[78]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[67]
Clodronate	DM9Y6X7	Approved	Clodronate affects the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[67]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[79]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[80]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[81]
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[82]
Acocantherin	DM7JT24	Approved	Acocantherin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[83]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[84]
Thalidomide	DM70BU5	Approved	Thalidomide increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[85]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[84]
Colchicine	DM2POTE	Approved	Colchicine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[86]
Sorafenib	DMS8IFC	Approved	Sorafenib increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[87]
Sertraline	DM0FB1J	Approved	Sertraline increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[88]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[79]
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[89]
Glucosamine	DM4ZLFD	Approved	Glucosamine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[90]
Isoniazid	DM5JVS3	Approved	Isoniazid decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[91]
Orlistat	DMRJSP8	Approved	Orlistat increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[92]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[93]
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[94]
Atazanavir	DMSYRBX	Approved	Atazanavir increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[95]
Penicillamine	DM40EF6	Approved	Penicillamine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[96]
Cantharidin	DMBP5N3	Approved	Cantharidin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[97]
Omeprazole	DM471KJ	Approved	Omeprazole increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[86]
Hesperetin	DMKER83	Approved	Hesperetin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[98]
Nilotinib	DM7HXWT	Approved	Nilotinib increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[99]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[79]
Nelfinavir mesylate	DMFX6G8	Approved	Nelfinavir mesylate increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[100]
Efavirenz	DMC0GSJ	Approved	Efavirenz increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[101]
Allopurinol	DMLPAOB	Approved	Allopurinol increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[74]
Ethacrynic acid	DM60QMR	Approved	Ethacrynic acid increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[102]
Ketamine	DMT5HA4	Approved	Ketamine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[103]
Olaparib	DM8QB1D	Approved	Olaparib increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[104]
Lamivudine	DMI347A	Approved	Lamivudine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[78]
Indinavir	DM0T3YH	Approved	Indinavir increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[74]
Furazolidone	DM3P6V7	Approved	Furazolidone increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[105]
Riboflavin	DM8YMWE	Approved	Riboflavin affects the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[106]
Tacrine	DM51FY6	Approved	Tacrine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[86]
Niflumic acid	DMJ3I1Q	Approved	Niflumic acid increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[107]
Hexachlorophene	DMLKSE0	Approved	Hexachlorophene increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[108]
Pyrazinamide	DM4IF32	Approved	Pyrazinamide increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[109]
Sibutramine	DMFJTDI	Approved	Sibutramine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[110]
Lomustine	DMMWSUL	Approved	Lomustine increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[86]
Bepridil	DM0RKS4	Approved	Bepridil increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[111]
Triacetin	DM0AEPG	Approved	Triacetin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[112]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[113]
Cibenzoline	DMBG0N4	Phase 4	Cibenzoline increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[111]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[108]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[114]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[115]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[116]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[117]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of DNA damage-inducible transcript 3 protein (DDIT3).	[118]

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