Details of Drug Off-Target (DOT)

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

• DOT Name: Tumor necrosis factor ligand superfamily member 6 (FASLG)
• Synonyms: Apoptosis antigen ligand; APTL; CD95 ligand; CD95-L; Fas antigen ligand; Fas ligand; FasL; CD antigen CD178
• Gene Name: FASLG
• Related Disease:
  Autoimmune lymphoproliferative syndrome type 1
  Autoimmune lymphoproliferative syndrome
• UniProt ID: TNFL6_HUMAN
• PDB ID: 4MSV; 5L19; 5L36
• Pfam ID: PF00229
• Sequence:
  MQQPFNYPYPQIYWVDSSASSPWAPPGTVLPCPTSVPRRPGQRRPPPPPPPPPLPPPPPP
  PPLPPLPLPPLKKRGNHSTGLCLLVMFFMVLVALVGLGLGMFQLFHLQKELAELRESTSQ
  MHTASSLEKQIGHPSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGG
  LVINETGLYFVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGKMMSYCTTGQMWA
  RSSYLGAVFNLTSADHLYVNVSELSLVNFEESQTFFGLYKL
• Function: Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells. Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development. Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses. TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance. Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis ; [Tumor necrosis factor ligand superfamily member 6, soluble form]: Induces FAS-mediated activation of NF-kappa-B, initiating non-apoptotic signaling pathways. Can induce apoptosis but does not appear to be essential for this process ; [FasL intracellular domain]: Cytoplasmic form induces gene transcription inhibition.
• KEGG Pathway:
  Platinum drug resistance (hsa01524)
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Cytokine-cytokine receptor interaction (hsa04060)
  FoxO sig.ling pathway (hsa04068)
  PI3K-Akt sig.ling pathway (hsa04151)
  Apoptosis (hsa04210)
  Necroptosis (hsa04217)
  .tural killer cell mediated cytotoxicity (hsa04650)
  Neurotrophin sig.ling pathway (hsa04722)
  Non-alcoholic fatty liver disease (hsa04932)
  Alcoholic liver disease (hsa04936)
  Type I diabetes mellitus (hsa04940)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Pathogenic Escherichia coli infection (hsa05130)
  Chagas disease (hsa05142)
  African trypanosomiasis (hsa05143)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  Human papillomavirus infection (hsa05165)
  Herpes simplex virus 1 infection (hsa05168)
  Human immunodeficiency virus 1 infection (hsa05170)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Autoimmune thyroid disease (hsa05320)
  Allograft rejection (hsa05330)
  Graft-versus-host disease (hsa05332)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Regulation by c-FLIP (R-HSA-3371378)
  RIPK1-mediated regulated necrosis (R-HSA-5213460)
  CASP8 activity is inhibited (R-HSA-5218900)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Dimerization of procaspase-8 (R-HSA-69416)
  FasL/ CD95L signaling (R-HSA-75157)
  Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models (R-HSA-8862803)
  FOXO-mediated transcription of cell death genes (R-HSA-9614657)
  Caspase activation via Death Receptors in the presence of ligand (R-HSA-140534)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune lymphoproliferative syndrome type 1	DISAFGRA	Strong	Autosomal recessive	[1]
Autoimmune lymphoproliferative syndrome	DISUG5ES	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate affects the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[17]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[18]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[19]
Etoposide	DMNH3PG	Approved	Etoposide increases the activity of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[20]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[21]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[22]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[23]
Mitomycin	DMH0ZJE	Approved	Mitomycin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[4]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[25]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[26]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[27]
Vinblastine	DM5TVS3	Approved	Vinblastine increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[28]
Acocantherin	DM7JT24	Approved	Acocantherin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[29]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[30]
Ritonavir	DMU764S	Approved	Ritonavir decreases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[32]
Bezafibrate	DMZDCS0	Approved	Bezafibrate affects the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[33]
Adenosine	DMM2NSK	Approved	Adenosine increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[34]
Ximelegatran	DMU8ANS	Approved	Ximelegatran decreases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[35]
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone affects the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[37]
Fructose	DM43AN2	Approved	Fructose increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[38]
Epinephrine	DM3KJBC	Approved	Epinephrine increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[39]
Acitretin	DM8BKU9	Approved	Acitretin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[40]
Octreotide	DMHIDCJ	Approved	Octreotide increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[41]
Regorafenib	DMHSY1I	Approved	Regorafenib increases the activity of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[42]
Uridine	DMQTREB	Approved	Uridine increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[34]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[43]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[44]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[45]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[33]
HMPL-004	DM29XGY	Phase 3	HMPL-004 increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[46]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[47]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[19]
Puerarin	DMJIMXH	Phase 2	Puerarin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[49]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[50]
VS-5584	DMMO3G5	Phase 1	VS-5584 increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[51]
Roxithromycin	DMVMIK2	Withdrawn from market	Roxithromycin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[52]
GM6001	DM7V9CT	Discontinued in Phase 2	GM6001 increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[53]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[54]
Dioscin	DM5H2W9	Preclinical	Dioscin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[55]
EMODIN	DMAEDQG	Terminated	EMODIN increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[56]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[57]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[58]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[59]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[38]
acrolein	DMAMCSR	Investigative	acrolein increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[27]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[60]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	3,7,3',4'-TETRAHYDROXYFLAVONE increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[61]
Morin	DM2OGZ5	Investigative	Morin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[62]
Aloe-emodin	DMPTY8S	Investigative	Aloe-emodin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[63]
Hyperforin	DM2L3PE	Investigative	Hyperforin increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[64]
Catechol	DML0YEK	Investigative	Catechol increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[19]
Flavanone	DMNWIYM	Investigative	Flavanone increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[65]
Deoxythymidine	DMR90HY	Investigative	Deoxythymidine increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[34]
Inosine	DMY65AR	Investigative	Inosine increases the expression of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Azacitidine	DMTA5OE	Approved	Azacitidine increases the response to substance of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[24]
Gefitinib	DM15F0X	Approved	Gefitinib increases the response to substance of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[31]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus decreases the secretion of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[36]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the secretion of Tumor necrosis factor ligand superfamily member 6 (FASLG).	[36]

References

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