Target Information

Target General Infomation
Target ID
T14592
Former ID
TTDI02199
Target Name
CD95
Gene Name
FAS
Synonyms
Apo-1 antigen; Apoptosis-mediating surface antigen FAS; FASLG receptor; Tumor necrosis factor receptor superfamily member 6; FAS
Target Type
Clinical Trial
Disease Cerebrovascular ischaemia [ICD9: 434.91; ICD10: I61-I63]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Glioblastoma multiforme [ICD9: 191; ICD10: C71]
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25]
Multiple myeloma [ICD9: 203; ICD10: C90]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Function
Receptor for TNFSF6/FASLG. The adapter molecule FADD recruitscaspase-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). {ECO:0000269|PubMed:19118384, ECO:0000269|PubMed:7533181}.
BioChemical Class
Cytokine receptor
UniProt ID
P25445
Sequence
MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCH
KPCPPGERKARDCTVNGDEPDCVPCQEGKEYTDKAHFSSKCRRCRLCDEGHGLEVEINCT
RTQNTKCRCKPNFFCNSTVCEHCDPCTKCEHGIIKECTLTSNTKCKEEGSRSNLGWLCLL
LLPIPLIVWVKRKEVQKTCRKHRKENQGSHESPTLNPETVAINLSDVDLSKYITTIAGVM
TLSQVKGFVRKNGVNEAKIDEIKNDNVQDTAEQKVQLLRNWHQLHGKKEAYDTLIKDLKK
ANLCTLAEKIQTIILKDITSDSENSNFRNEIQSLV
Drugs and Mode of Action
Drug(s) APG-101 Drug Info Phase 2 Cerebrovascular ischaemia [522954]
DE-098 Drug Info Phase 2 Rheumatoid arthritis [547480]
VB-111 Drug Info Phase 2 Glioblastoma multiforme [531640]
APO-010 Drug Info Phase 1 Multiple myeloma [531313]
Inhibitor APG-101 Drug Info [531855]
APG-103 Drug Info [543515]
Binder APO-010 Drug Info [531313]
Modulator VB-111 Drug Info
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway MAPK signaling pathway
Cytokine-cytokine receptor interaction
p53 signaling pathway
Apoptosis
Natural killer cell mediated cytotoxicity
TNF signaling pathway
Non-alcoholic fatty liver disease (NAFLD)
Type I diabetes mellitus
Alzheimer&#039
s disease
Chagas disease (American trypanosomiasis)
African trypanosomiasis
Hepatitis B
Measles
Influenza A
Herpes simplex infection
Pathways in cancer
Proteoglycans in cancer
Autoimmune thyroid disease
Allograft rejection
Graft-versus-host disease
NetPath Pathway IL2 Signaling Pathway
TCR Signaling Pathway
PANTHER Pathway Apoptosis signaling pathway
FAS signaling pathway
p53 pathway
Pathway Interaction Database p73 transcription factor network
FAS (CD95) signaling pathway
Direct p53 effectors
Negative effector of Fas and TNF-alpha
Caspase Cascade in Apoptosis
Validated transcriptional targets of TAp63 isoforms
Reactome FasL/ CD95L signaling
WikiPathways DNA Damage Response
TCR Signaling Pathway
Apoptosis Modulation by HSP70
MAPK Signaling Pathway
FAS pathway and Stress induction of HSP regulation
Apoptosis
Integrated Pancreatic Cancer Pathway
Adipogenesis
Allograft Rejection
Alzheimers Disease
Extrinsic Pathway for Apoptosis
Apoptosis Modulation and Signaling
miRNA Regulation of DNA Damage Response
References
Ref 522954ClinicalTrials.gov (NCT01071837) APG101 in Glioblastoma. U.S. National Institutes of Health.
Ref 531313APO010, a synthetic hexameric CD95 ligand, induces human glioma cell death in vitro and in vivo. Neuro Oncol. 2011 Feb;13(2):155-64.
Ref 531640VB-111 for cancer. Expert Opin Biol Ther. 2011 Dec;11(12):1669-76.
Ref 547480Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016731)
Ref 531313APO010, a synthetic hexameric CD95 ligand, induces human glioma cell death in vitro and in vivo. Neuro Oncol. 2011 Feb;13(2):155-64.
Ref 531855Pharmacokinetics, 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.
Ref 543515(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).
Ref 550368ARG098, 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.

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