Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTF0RCZ)

DTT Name	Apoptosis mediating surface antigen FAS (FAS)
Synonyms	Tumor necrosis factor receptor superfamily member 6; TNFRSF6; FASLG receptor; FAS1; CD95; Apoptosis-mediating surface antigen FAS; Apo-1 antigen; APT1
Gene Name	FAS
DTT Type	Clinical trial target	[1]
BioChemical Class	Cytokine receptor
UniProt ID	TNR6_HUMAN
TTD ID	T14592
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Sequence	MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCH KPCPPGERKARDCTVNGDEPDCVPCQEGKEYTDKAHFSSKCRRCRLCDEGHGLEVEINCT RTQNTKCRCKPNFFCNSTVCEHCDPCTKCEHGIIKECTLTSNTKCKEEGSRSNLGWLCLL LLPIPLIVWVKRKEVQKTCRKHRKENQGSHESPTLNPETVAINLSDVDLSKYITTIAGVM TLSQVKGFVRKNGVNEAKIDEIKNDNVQDTAEQKVQLLRNWHQLHGKKEAYDTLIKDLKK ANLCTLAEKIQTIILKDITSDSENSNFRNEIQSLV
Function	The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro). Receptor for TNFSF6/FASLG.
KEGG Pathway	MAPK signaling pathway (hsa04010 ) Cytokine-cytokine receptor interaction (hsa04060 ) p53 signaling pathway (hsa04115 ) Apoptosis (hsa04210 ) Natural killer cell mediated cytotoxicity (hsa04650 ) TNF signaling pathway (hsa04668 ) Non-alcoholic fatty liver disease (NAFLD) (hsa04932 ) Type I diabetes mellitus (hsa04940 ) Alzheimer's disease (hsa05010 ) Chagas disease (American trypanosomiasis) (hsa05142 ) African trypanosomiasis (hsa05143 ) Hepatitis B (hsa05161 ) Measles (hsa05162 ) Influenza A (hsa05164 ) Herpes simplex infection (hsa05168 ) Pathways in cancer (hsa05200 ) Proteoglycans in cancer (hsa05205 ) Autoimmune thyroid disease (hsa05320 ) Allograft rejection (hsa05330 ) Graft-versus-host disease (hsa05332 )
Reactome Pathway	FasL/ CD95L signaling (R-HSA-75157 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DTT

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VB-111	DMX04CA	Malignant glioma	2A00.0	Phase 3	[1]
APG-101	DM0FXMZ	Cerebrovascular ischaemia	8B1Z	Phase 2	[2]
DE-098	DM5XT3G	Rheumatoid arthritis	FA20	Phase 2	[3]
APO-010	DMPJBCR	Multiple myeloma	2A83	Phase 1	[4]
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3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-aminophenoxazine-3-one	DMBVGAO	T-cell leukaemia	2A90	Investigative	[5]
APG-103	DMR93WE	Inflammation	1A00-CA43.1	Investigative	[6]
F61F12	DMD7HO8	Solid tumour/cancer	2A00-2F9Z	Investigative	[6]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Multiple myeloma	2C82	Bone marrow	1.08E-03	-0.69	-2.65
Glioma	2C82	Brainstem tissue	1.66E-01	1.75	2.08
Glioma	2C82	White matter	4.18E-01	-0.25	-0.43
Rheumatoid arthritis	FA20	Synovial tissue	9.19E-11	1.55	4.58
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References

1	Phase I dose-escalation study of VB-111, an antiangiogenic virotherapy, in patients with advanced solid tumors.Clin Cancer Res.2013 Jul 15;19(14):3996-4007.
2	Pharmacokinetics, pharmacodynamics, safety and tolerability of APG101, a CD95-Fc fusion protein, in healthy volunteers and two glioma patients. Int Immunopharmacol. 2012 May;13(1):93-100.
3	ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model. BMC Musculoskeletal Disorders 2010,11:221.
4	APO010, a synthetic hexameric CD95 ligand, induces human glioma cell death in vitro and in vivo. Neuro Oncol. 2011 Feb;13(2):155-64.
5	Apoptosis as a mechanism for the treatment of adult T cell leukemia: promising drugs from benchside to bedside. Drug Discov Today. 2020 Jul;25(7):1189-1197.
6	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1875).