Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV7GFHH)

• DOT Name: FAS-associated death domain protein (FADD)
• Synonyms: FAS-associating death domain-containing protein; Growth-inhibiting gene 3 protein; Mediator of receptor induced toxicity
• Gene Name: FADD
• Related Disease:
  Esophageal squamous cell carcinoma
  Lymphoblastic lymphoma
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Advanced cancer
  Autoimmune lymphoproliferative syndrome type 1
  Autoimmune lymphoproliferative syndrome type 2B
  Bacterial infection
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  FADD-related immunodeficiency
  Glioblastoma multiforme
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Lung neoplasm
  Malignant glioma
  Melanoma
  Neoplasm
  Nervous system inflammation
  Non-small-cell lung cancer
  Osteosarcoma
  Rheumatoid arthritis
  Small lymphocytic lymphoma
  Squamous cell carcinoma
  Adenocarcinoma
  Breast neoplasm
  Carcinoma of liver and intrahepatic biliary tract
  Gastric cancer
  Glioma
  Liver cancer
  Type-1 diabetes
  Type-1/2 diabetes
  High blood pressure
  Colorectal carcinoma
  Obesity
  Osteoarthritis
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
  Sensorineural hearing loss disorder
  Stomach cancer
• UniProt ID: FADD_HUMAN
• PDB ID: 1A1W; 1A1Z; 1E3Y; 1E41; 2GF5; 3EZQ; 3OQ9; 6ACI; 7LXC
• Pfam ID: PF00531 ; PF01335
• Sequence:
  MDPFLVLLHSVSSSLSSSELTELKFLCLGRVGKRKLERVQSGLDLFSMLLEQNDLEPGHT
  ELLRELLASLRRHDLLRRVDDFEAGAAAGAAPGEEDLCAAFNVICDNVGKDWRRLARQLK
  VSDTKIDSIEDRYPRNLTERVRESLRIWKNTEKENATVAHLVGALRSCQMNLVADLVQEV
  QQARDLQNRSGAMSPMSWNSDASTSEAS
• Function: Apoptotic adapter molecule that recruits caspases CASP8 or CASP10 to the activated FAS/CD95 or TNFRSF1A/TNFR-1 receptors. The resulting aggregate called the death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. Active CASP8 initiates the subsequent cascade of caspases mediating apoptosis. Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling.
• Tissue Specificity: Expressed in a wide variety of tissues, except for peripheral blood mononuclear leukocytes.
• KEGG Pathway:
  Platinum drug resistance (hsa01524)
  Apoptosis (hsa04210)
  Apoptosis - multiple species (hsa04215)
  Necroptosis (hsa04217)
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  RIG-I-like receptor sig.ling pathway (hsa04622)
  Cytosolic D.-sensing pathway (hsa04623)
  IL-17 sig.ling pathway (hsa04657)
  TNF sig.ling pathway (hsa04668)
  Alcoholic liver disease (hsa04936)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Pathogenic Escherichia coli infection (hsa05130)
  Salmonella infection (hsa05132)
  Chagas disease (hsa05142)
  Tuberculosis (hsa05152)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  Human papillomavirus infection (hsa05165)
  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)
• Reactome Pathway:
  TRIF-mediated programmed cell death (R-HSA-2562578)
  Regulation by c-FLIP (R-HSA-3371378)
  RIPK1-mediated regulated necrosis (R-HSA-5213460)
  CASP8 activity is inhibited (R-HSA-5218900)
  TNFR1-induced proapoptotic signaling (R-HSA-5357786)
  Regulation of TNFR1 signaling (R-HSA-5357905)
  Regulation of necroptotic cell death (R-HSA-5675482)
  Dimerization of procaspase-8 (R-HSA-69416)
  FasL/ CD95L signaling (R-HSA-75157)
  TRAIL signaling (R-HSA-75158)
  TLR3-mediated TICAM1-dependent programmed cell death (R-HSA-9013957)
  NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 (R-HSA-933543)
  Defective RIPK1-mediated regulated necrosis (R-HSA-9693928)
  Caspase activation via Death Receptors in the presence of ligand (R-HSA-140534)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Biomarker	[1]
Lymphoblastic lymphoma	DISB9ZYC	Definitive	Biomarker	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Autoimmune lymphoproliferative syndrome type 1	DISAFGRA	Strong	Genetic Variation	[5]
Autoimmune lymphoproliferative syndrome type 2B	DIS7EXGM	Strong	Altered Expression	[6]
Bacterial infection	DIS5QJ9S	Strong	Altered Expression	[7]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Genetic Variation	[10]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[10]
FADD-related immunodeficiency	DISLH7O6	Strong	Autosomal recessive	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[12]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Lung neoplasm	DISVARNB	Strong	Posttranslational Modification	[15]
Malignant glioma	DISFXKOV	Strong	Biomarker	[16]
Melanoma	DIS1RRCY	Strong	Altered Expression	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[19]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[20]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[8]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[21]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[22]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[23]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[24]
Breast neoplasm	DISNGJLM	moderate	Posttranslational Modification	[25]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Genetic Variation	[26]
Gastric cancer	DISXGOUK	moderate	Biomarker	[27]
Glioma	DIS5RPEH	moderate	Altered Expression	[28]
Liver cancer	DISDE4BI	moderate	Genetic Variation	[26]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[29]
Type-1/2 diabetes	DISIUHAP	moderate	Altered Expression	[30]
High blood pressure	DISY2OHH	Disputed	Therapeutic	[31]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[32]
Obesity	DIS47Y1K	Limited	Biomarker	[33]
Osteoarthritis	DIS05URM	Limited	Biomarker	[34]
Parkinson disease	DISQVHKL	Limited	Biomarker	[35]
Prostate cancer	DISF190Y	Limited	Posttranslational Modification	[36]
Prostate carcinoma	DISMJPLE	Limited	Posttranslational Modification	[36]
Sensorineural hearing loss disorder	DISJV45Z	Limited	Biomarker	[37]
Stomach cancer	DISKIJSX	Limited	Biomarker	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	FAS-associated death domain protein (FADD) increases the response to substance of Resveratrol.	[76]
PMID26394986-Compound-22	DM43Z1G	Patented	FAS-associated death domain protein (FADD) affects the response to substance of PMID26394986-Compound-22.	[77]

36 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 FAS-associated death domain protein (FADD).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of FAS-associated death domain protein (FADD).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of FAS-associated death domain protein (FADD).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of FAS-associated death domain protein (FADD).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of FAS-associated death domain protein (FADD).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of FAS-associated death domain protein (FADD).	[43]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of FAS-associated death domain protein (FADD).	[44]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of FAS-associated death domain protein (FADD).	[45]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of FAS-associated death domain protein (FADD).	[46]
Marinol	DM70IK5	Approved	Marinol decreases the expression of FAS-associated death domain protein (FADD).	[47]
Selenium	DM25CGV	Approved	Selenium increases the expression of FAS-associated death domain protein (FADD).	[48]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of FAS-associated death domain protein (FADD).	[49]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of FAS-associated death domain protein (FADD).	[50]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of FAS-associated death domain protein (FADD).	[51]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of FAS-associated death domain protein (FADD).	[52]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of FAS-associated death domain protein (FADD).	[53]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of FAS-associated death domain protein (FADD).	[54]
Acocantherin	DM7JT24	Approved	Acocantherin increases the expression of FAS-associated death domain protein (FADD).	[55]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial decreases the expression of FAS-associated death domain protein (FADD).	[56]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium decreases the expression of FAS-associated death domain protein (FADD).	[56]
Dactinomycin	DM2YGNW	Approved	Dactinomycin decreases the expression of FAS-associated death domain protein (FADD).	[40]
Adenosine	DMM2NSK	Approved	Adenosine decreases the expression of FAS-associated death domain protein (FADD).	[57]
Dipyridamole	DMXY30O	Approved	Dipyridamole increases the expression of FAS-associated death domain protein (FADD).	[57]
Acitretin	DM8BKU9	Approved	Acitretin increases the expression of FAS-associated death domain protein (FADD).	[58]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of FAS-associated death domain protein (FADD).	[60]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of FAS-associated death domain protein (FADD).	[62]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of FAS-associated death domain protein (FADD).	[63]
Dioscin	DM5H2W9	Preclinical	Dioscin increases the expression of FAS-associated death domain protein (FADD).	[65]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of FAS-associated death domain protein (FADD).	[66]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of FAS-associated death domain protein (FADD).	[67]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of FAS-associated death domain protein (FADD).	[68]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of FAS-associated death domain protein (FADD).	[69]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid affects the expression of FAS-associated death domain protein (FADD).	[70]
Morin	DM2OGZ5	Investigative	Morin increases the expression of FAS-associated death domain protein (FADD).	[71]
Naringin	DM4DG1Y	Investigative	Naringin increases the expression of FAS-associated death domain protein (FADD).	[74]
Acacetin	DMQOB0X	Investigative	Acacetin decreases the expression of FAS-associated death domain protein (FADD).	[75]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Aminolevulinic acid hci	DMS4BLQ	Approved	Aminolevulinic acid hci increases the phosphorylation of FAS-associated death domain protein (FADD).	[59]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of FAS-associated death domain protein (FADD).	[61]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of FAS-associated death domain protein (FADD).	[64]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of FAS-associated death domain protein (FADD).	[64]
2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One	DMDN12L	Investigative	2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One decreases the phosphorylation of FAS-associated death domain protein (FADD).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Syringic Acid	DM802V7	Investigative	Syringic Acid increases the secretion of FAS-associated death domain protein (FADD).	[73]

References

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