Details of Drug Off-Target (DOT)

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

• DOT Name: BH3-interacting domain death agonist (BID)
• Synonyms: p22 BID; BID
• Gene Name: BID
• Related Disease:
  Melanoma
  Stroke
  Adenoma
  B-cell neoplasm
  Bipolar disorder
  Bronchopulmonary dysplasia
  Carcinoma
  Cardiovascular disease
  Castration-resistant prostate carcinoma
  Colonic neoplasm
  Colorectal carcinoma
  Coronary heart disease
  Cystic fibrosis
  Fatty liver disease
  Gastric cancer
  Gastric neoplasm
  Hepatocellular carcinoma
  Hereditary diffuse gastric adenocarcinoma
  Lung carcinoma
  Lung neoplasm
  Myocardial infarction
  Neoplasm
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Obesity
  Oral cancer
  Prostate cancer
  Prostate carcinoma
  Small lymphocytic lymphoma
  Stomach cancer
  Systemic lupus erythematosus
  Triple negative breast cancer
  Bacterial infection
  Breast cancer
  Breast carcinoma
  Chronic obstructive pulmonary disease
  Colitis
  Acute myelogenous leukaemia
  Adenocarcinoma
  Advanced cancer
  Asthma
  Breast neoplasm
  Schizophrenia
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Type-1/2 diabetes
• UniProt ID: BID_HUMAN
• PDB ID: 1ZY3; 2BID; 2KBW; 2M5B; 2M5I; 4BD2; 4QVE; 4ZEQ; 4ZIG; 4ZII; 5AJJ; 5C3F; 7M5A; 7M5B; 7P33; 7QTW
• Pfam ID: PF06393
• Sequence:
  MDCEVNNGSSLRDECITNLLVFGFLQSCSDNSFRRELDALGHELPVLAPQWEGYDELQTD
  GNRSSHSRLGRIEADSESQEDIIRNIARHLAQVGDSMDRSIPPGLVNGLALQLRNTSRSE
  EDRNRDLATALEQLLQAYPRDMEKEKTMLVLALLLAKKVASHTPSLLRDVFHTTVNFINQ
  NLRTYVRSLARNGMD
• Function: Induces caspases and apoptosis. Counters the protective effect of BCL2; [BH3-interacting domain death agonist p15]: Induces caspase activation and apoptosis. Allows the release of cytochrome c ; [Isoform 1]: Induces ICE-like proteases and apoptosis; [Isoform 2]: Induces ICE-like proteases and apoptosis; [Isoform 3]: Does not induce apoptosis; [Isoform 4]: Induces ICE-like proteases and apoptosis.
• Tissue Specificity: .Expressed in spleen, pancreas and placenta (at protein level).; [Isoform 3]: Expressed in lung, pancreas and spleen (at protein level).; [Isoform 4]: Expressed in lung and pancreas (at protein level).
• KEGG Pathway:
  Platinum drug resistance (hsa01524)
  Sphingolipid sig.ling pathway (hsa04071)
  p53 sig.ling pathway (hsa04115)
  Apoptosis (hsa04210)
  Apoptosis - multiple species (hsa04215)
  Necroptosis (hsa04217)
  .tural killer cell mediated cytotoxicity (hsa04650)
  Non-alcoholic fatty liver disease (hsa04932)
  Alzheimer disease (hsa05010)
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Tuberculosis (hsa05152)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Pathways in cancer (hsa05200)
  Viral myocarditis (hsa05416)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Activation and oligomerization of BAK protein (R-HSA-111452)
  BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members (R-HSA-111453)
  Activation, translocation and oligomerization of BAX (R-HSA-114294)
  TP53 Regulates Transcription of Genes Involved in Cytochrome C Release (R-HSA-6803204)
  Activation, myristolyation of BID and translocation to mitochondria (R-HSA-75108)
  Activation of BAD and translocation to mitochondria (R-HSA-111447)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Biomarker	[1]
Stroke	DISX6UHX	Definitive	Biomarker	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[3]
B-cell neoplasm	DISVY326	Strong	Biomarker	[4]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Biomarker	[6]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[7]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[8]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[9]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[11]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[12]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[13]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[7]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[16]
Lung neoplasm	DISVARNB	Strong	Biomarker	[17]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[18]
Neoplasm	DISZKGEW	Strong	Altered Expression	[19]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[21]
Obesity	DIS47Y1K	Strong	Biomarker	[22]
Oral cancer	DISLD42D	Strong	Genetic Variation	[23]
Prostate cancer	DISF190Y	Strong	Altered Expression	[24]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[24]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[25]
Stomach cancer	DISKIJSX	Strong	Biomarker	[7]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[26]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[27]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[28]
Breast cancer	DIS7DPX1	moderate	Biomarker	[9]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[9]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[29]
Colitis	DISAF7DD	moderate	Biomarker	[28]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[30]
Adenocarcinoma	DIS3IHTY	Limited	Genetic Variation	[31]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[32]
Asthma	DISW9QNS	Limited	Biomarker	[33]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[34]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[35]
Thyroid cancer	DIS3VLDH	Limited	Biomarker	[36]
Thyroid gland carcinoma	DISMNGZ0	Limited	Biomarker	[36]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[36]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	BH3-interacting domain death agonist (BID) decreases the response to substance of Fluorouracil.	[7]
Topotecan	DMP6G8T	Approved	BH3-interacting domain death agonist (BID) affects the response to substance of Topotecan.	[111]

55 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 BH3-interacting domain death agonist (BID).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of BH3-interacting domain death agonist (BID).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of BH3-interacting domain death agonist (BID).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of BH3-interacting domain death agonist (BID).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BH3-interacting domain death agonist (BID).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of BH3-interacting domain death agonist (BID).	[43]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of BH3-interacting domain death agonist (BID).	[44]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of BH3-interacting domain death agonist (BID).	[45]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of BH3-interacting domain death agonist (BID).	[46]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of BH3-interacting domain death agonist (BID).	[47]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of BH3-interacting domain death agonist (BID).	[48]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of BH3-interacting domain death agonist (BID).	[50]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of BH3-interacting domain death agonist (BID).	[51]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of BH3-interacting domain death agonist (BID).	[52]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of BH3-interacting domain death agonist (BID).	[54]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of BH3-interacting domain death agonist (BID).	[55]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of BH3-interacting domain death agonist (BID).	[44]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of BH3-interacting domain death agonist (BID).	[59]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the activity of BH3-interacting domain death agonist (BID).	[61]
Menthol	DMG2KW7	Approved	Menthol increases the expression of BH3-interacting domain death agonist (BID).	[63]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of BH3-interacting domain death agonist (BID).	[65]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of BH3-interacting domain death agonist (BID).	[66]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of BH3-interacting domain death agonist (BID).	[67]
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the expression of BH3-interacting domain death agonist (BID).	[68]
Melatonin	DMKWFBT	Approved	Melatonin increases the expression of BH3-interacting domain death agonist (BID).	[70]
Dextroamphetamine	DMMIHVP	Approved	Dextroamphetamine increases the expression of BH3-interacting domain death agonist (BID).	[68]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of BH3-interacting domain death agonist (BID).	[72]
Rigosertib	DMOSTXF	Phase 3	Rigosertib decreases the expression of BH3-interacting domain death agonist (BID).	[73]
HMPL-004	DM29XGY	Phase 3	HMPL-004 increases the expression of BH3-interacting domain death agonist (BID).	[74]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of BH3-interacting domain death agonist (BID).	[75]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone decreases the expression of BH3-interacting domain death agonist (BID).	[76]
Delphinidin	DMS2WIN	Phase 2	Delphinidin decreases the expression of BH3-interacting domain death agonist (BID).	[78]
PF-04991532	DM94NBE	Phase 2	PF-04991532 decreases the expression of BH3-interacting domain death agonist (BID).	[79]
Phenoxodiol	DMBUJVX	Phase 1/2	Phenoxodiol increases the activity of BH3-interacting domain death agonist (BID).	[81]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of BH3-interacting domain death agonist (BID).	[82]
Tetrandrine	DMAOJBX	Phase 1	Tetrandrine decreases the expression of BH3-interacting domain death agonist (BID).	[83]
OBP-801	DMPLV9G	Phase 1	OBP-801 increases the activity of BH3-interacting domain death agonist (BID).	[84]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of BH3-interacting domain death agonist (BID).	[86]
Dioscin	DM5H2W9	Preclinical	Dioscin decreases the expression of BH3-interacting domain death agonist (BID).	[87]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of BH3-interacting domain death agonist (BID).	[91]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the expression of BH3-interacting domain death agonist (BID).	[92]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of BH3-interacting domain death agonist (BID).	[93]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of BH3-interacting domain death agonist (BID).	[94]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of BH3-interacting domain death agonist (BID).	[95]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of BH3-interacting domain death agonist (BID).	[96]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of BH3-interacting domain death agonist (BID).	[97]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the expression of BH3-interacting domain death agonist (BID).	[100]
Taurine	DMVW7N3	Investigative	Taurine decreases the expression of BH3-interacting domain death agonist (BID).	[103]
Staurosporine	DM0E9BR	Investigative	Staurosporine increases the expression of BH3-interacting domain death agonist (BID).	[70]
gingerol	DMNXYSM	Investigative	gingerol decreases the expression of BH3-interacting domain death agonist (BID).	[104]
PATULIN	DM0RV9C	Investigative	PATULIN increases the expression of BH3-interacting domain death agonist (BID).	[105]
NORCANTHARIDIN	DM9B6Y1	Investigative	NORCANTHARIDIN increases the expression of BH3-interacting domain death agonist (BID).	[106]
MANGOSTIN	DMYQGDV	Investigative	MANGOSTIN decreases the expression of BH3-interacting domain death agonist (BID).	[107]
Methylenedioxymethamphetamine	DMYVU47	Investigative	Methylenedioxymethamphetamine increases the expression of BH3-interacting domain death agonist (BID).	[68]
2-Amino-1-(4-methylthiophenyl)propane	DMJ2Z9G	Investigative	2-Amino-1-(4-methylthiophenyl)propane increases the expression of BH3-interacting domain death agonist (BID).	[68]

21 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Vorinostat	DMWMPD4	Approved	Vorinostat increases the cleavage of BH3-interacting domain death agonist (BID).	[49]
Selenium	DM25CGV	Approved	Selenium increases the cleavage of BH3-interacting domain death agonist (BID).	[53]
Bortezomib	DMNO38U	Approved	Bortezomib increases the cleavage of BH3-interacting domain death agonist (BID).	[56]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the cleavage of BH3-interacting domain death agonist (BID).	[57]
Aspirin	DM672AH	Approved	Aspirin increases the cleavage of BH3-interacting domain death agonist (BID).	[58]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the cleavage of BH3-interacting domain death agonist (BID).	[60]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the cleavage of BH3-interacting domain death agonist (BID).	[62]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the cleavage of BH3-interacting domain death agonist (BID).	[64]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the cleavage of BH3-interacting domain death agonist (BID).	[69]
Sanguinarine	DMDINFS	Approved	Sanguinarine increases the cleavage of BH3-interacting domain death agonist (BID).	[71]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol increases the cleavage of BH3-interacting domain death agonist (BID).	[77]
STX-140	DMJK5CT	Phase 2	STX-140 increases the cleavage of BH3-interacting domain death agonist (BID).	[80]
PMID26394986-Compound-22	DM43Z1G	Patented	PMID26394986-Compound-22 increases the cleavage of BH3-interacting domain death agonist (BID).	[85]
M-carboxycinnamic acid bishydroxamide	DMHJLPS	Preclinical	M-carboxycinnamic acid bishydroxamide increases the cleavage of BH3-interacting domain death agonist (BID).	[88]
EMODIN	DMAEDQG	Terminated	EMODIN increases the degradation of BH3-interacting domain death agonist (BID).	[89]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the cleavage of BH3-interacting domain death agonist (BID).	[98]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid increases the cleavage of BH3-interacting domain death agonist (BID).	[99]
	DM9CEI5		increases the cleavage of BH3-interacting domain death agonist (BID).	[101]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	3,7,3',4'-TETRAHYDROXYFLAVONE increases the cleavage of BH3-interacting domain death agonist (BID).	[102]
Bafilomycin A1	DMUNK59	Investigative	Bafilomycin A1 increases the cleavage of BH3-interacting domain death agonist (BID).	[108]
BADGE	DMCK5DG	Investigative	BADGE increases the cleavage of BH3-interacting domain death agonist (BID).	[109]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of BH3-interacting domain death agonist (BID).	[90]

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