Target Information

Target General Information

Target ID

T14592 (Former ID: TTDI02199)

Target 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

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Brain cancer [ICD-11: 2A00]

Ovarian cancer [ICD-11: 2C73]

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.

Click to Show/Hide

BioChemical Class

Cytokine receptor

UniProt ID

TNR6_HUMAN

Sequence

MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCH
KPCPPGERKARDCTVNGDEPDCVPCQEGKEYTDKAHFSSKCRRCRLCDEGHGLEVEINCT
RTQNTKCRCKPNFFCNSTVCEHCDPCTKCEHGIIKECTLTSNTKCKEEGSRSNLGWLCLL
LLPIPLIVWVKRKEVQKTCRKHRKENQGSHESPTLNPETVAINLSDVDLSKYITTIAGVM
TLSQVKGFVRKNGVNEAKIDEIKNDNVQDTAEQKVQLLRNWHQLHGKKEAYDTLIKDLKK
ANLCTLAEKIQTIILKDITSDSENSNFRNEIQSLV

Click to Show/Hide

3D Structure

Click to Show 3D Structure of This Target

AlphaFold

HIT2.0 ID

T57HGP

Drugs and Modes of Action

Top

Clinical Trial Drug(s)

[+] 4 Clinical Trial Drugs

VB-111

Drug Info

Phase 3

Malignant glioma

[2]

APG-101

Drug Info

Phase 2

Cerebrovascular ischaemia

[3]

DE-098

Drug Info

Phase 2

Rheumatoid arthritis

[4]

APO-010

Drug Info

Phase 1

Multiple myeloma

[5]

Mode of Action

[+] 4 Modes of Action

Modulator

[+] 1 Modulator drugs

VB-111

Drug Info

[1]

Inhibitor

[+] 2 Inhibitor drugs

APG-101

Drug Info

[6]

APG-103

Drug Info

[9]

Binder

[+] 1 Binder drugs

APO-010

Drug Info

[5]

Activator

[+] 1 Activator drugs

2-aminophenoxazine-3-one

Drug Info

[8]

Target Regulators

Top

Target-regulating microRNAs

Target-regulating microRNAs Info

Target-regulating Transcription Factors

Target-regulating Transcription Factors Info

Target-interacting Proteins

Target-interacting Proteins Info

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 20 KEGG Pathways	+
1	MAPK signaling pathway
2	Cytokine-cytokine receptor interaction
3	p53 signaling pathway
4	Apoptosis
5	Natural killer cell mediated cytotoxicity
6	TNF signaling pathway
7	Non-alcoholic fatty liver disease (NAFLD)
8	Type I diabetes mellitus
9	Alzheimer's disease
10	Chagas disease (American trypanosomiasis)
11	African trypanosomiasis
12	Hepatitis B
13	Measles
14	Influenza A
15	Herpes simplex infection
16	Pathways in cancer
17	Proteoglycans in cancer
18	Autoimmune thyroid disease
19	Allograft rejection
20	Graft-versus-host disease
NetPath Pathway	[+] 2 NetPath Pathways	+
1	IL2 Signaling Pathway
2	TCR Signaling Pathway
Panther Pathway	[+] 3 Panther Pathways	+
1	Apoptosis signaling pathway
2	FAS signaling pathway
3	p53 pathway
PID Pathway	[+] 6 PID Pathways	+
1	p73 transcription factor network
2	FAS (CD95) signaling pathway
3	Direct p53 effectors
4	HIV-1 Nef: Negative effector of Fas and TNF-alpha
5	Caspase Cascade in Apoptosis
6	Validated transcriptional targets of TAp63 isoforms
Reactome	[+] 1 Reactome Pathways	+
1	FasL/ CD95L signaling
WikiPathways	[+] 13 WikiPathways	+
1	DNA Damage Response
2	TCR Signaling Pathway
3	Apoptosis Modulation by HSP70
4	MAPK Signaling Pathway
5	FAS pathway and Stress induction of HSP regulation
6	Apoptosis
7	Integrated Pancreatic Cancer Pathway
8	Adipogenesis
9	Allograft Rejection
10	Alzheimers Disease
11	Extrinsic Pathway for Apoptosis
12	Apoptosis Modulation and Signaling
13	miRNA Regulation of DNA Damage Response

References

Top

REF 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.

REF 2

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 3

ClinicalTrials.gov (NCT01071837) APG101 in Glioblastoma. U.S. National Institutes of Health.

REF 4

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016731)

REF 5

APO010, a synthetic hexameric CD95 ligand, induces human glioma cell death in vitro and in vivo. Neuro Oncol. 2011 Feb;13(2):155-64.

REF 6

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.

REF 7

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.

REF 8

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.

REF 9

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).

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Yuzong CHEN

Prof. Feng ZHU