Target Information

Target General Information

Target ID

T86552 (Former ID: TTDNC00502)

Target Name

Tumor necrosis factor receptor type I (TNF-R1)

Synonyms

p60; p55; Tumor necrosis factor-binding protein 1; Tumor necrosis factor receptor superfamily member 1A; Tumor necrosis factor receptor 1; TNFR1; TNFR-I; TNFAR; TNF-RI; TBPI; CD120a

Gene Name

TNFRSF1A

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. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase. Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha.

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BioChemical Class

Cytokine receptor

UniProt ID

TNR1A_HUMAN

Sequence

MGLSTVPDLLLPLVLLELLVGIYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCT
KCHKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVD
RDTVCGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECV
SCSNCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVIFFGLCLLSLLFIGLMYRYQRWK
SKLYSIVCGKSTPEKEGELEGTTTKPLAPNPSFSPTPGFTPTLGFSPVPSSTFTSSSTYT
PGDCPNFAAPRREVAPPYQGADPILATALASDPIPNPLQKWEDSAHKPQSLDTDDPATLY
AVVENVPPLRWKEFVRRLGLSDHEIDRLELQNGRCLREAQYSMLATWRRRTPRREATLEL
LGRVLRDMDLLGCLEDIEEALCGPAALPPAPSLLR

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3D Structure

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AlphaFold

ADReCS ID

BADD_A01877 ; BADD_A05438

HIT2.0 ID

T16KVU

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 4 Clinical Trial Drugs

VB-111

Drug Info

Phase 3

Malignant glioma

[2]

Drug 2862277

Drug Info

Phase 2

Acute lung injury

[3]

AVX-470

Drug Info

Phase 1

Inflammatory bowel disease

[4]

GSK1995057

Drug Info

Phase 1

Adult respiratory distress syndrome

[5]

Discontinued Drug(s)

[+] 1 Discontinued Drugs

Anti-IFN gamma

Drug Info

Terminated

Alopecia

[6]

Mode of Action

[+] 1 Modes of Action

Modulator

[+] 6 Modulator drugs

VB-111

Drug Info

[1]

ALF-421

Drug Info

[8]

NM-2014

Drug Info

[7]

Recombinant human TNF receptor

Drug Info

[8]

TNFcept

Drug Info

[8]

TNFR1 NAM

Drug Info

[7]

Chemical Structure based Activity Landscape of Target

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Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

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Target-interacting Proteins

Target-interacting Proteins Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 18 KEGG Pathways	+
1	MAPK signaling pathway
2	Cytokine-cytokine receptor interaction
3	NF-kappa B signaling pathway
4	Sphingolipid signaling pathway
5	Apoptosis
6	Osteoclast differentiation
7	TNF signaling pathway
8	Adipocytokine signaling pathway
9	Non-alcoholic fatty liver disease (NAFLD)
10	Alzheimer's disease
11	Amyotrophic lateral sclerosis (ALS)
12	Chagas disease (American trypanosomiasis)
13	Toxoplasmosis
14	Tuberculosis
15	Hepatitis C
16	Influenza A
17	HTLV-I infection
18	Herpes simplex infection
NetPath Pathway	[+] 2 NetPath Pathways	+
1	TGF_beta_Receptor Signaling Pathway
2	TCR Signaling Pathway
Panther Pathway	[+] 1 Panther Pathways	+
1	Apoptosis signaling pathway
PID Pathway	[+] 6 PID Pathways	+
1	Canonical NF-kappaB pathway
2	Signaling events mediated by HDAC Class I
3	TNF receptor signaling pathway
4	Ceramide signaling pathway
5	HIV-1 Nef: Negative effector of Fas and TNF-alpha
6	Caspase Cascade in Apoptosis
Reactome	[+] 6 Reactome Pathways	+
1	TNFR1-induced proapoptotic signaling
2	Regulation of TNFR1 signaling
3	TNFR1-induced NFkappaB signaling pathway
4	TNFR1-mediated ceramide production
5	TNFs bind their physiological receptors
6	TNF signaling
WikiPathways	[+] 11 WikiPathways	+
1	Inflammatory Response Pathway
2	Apoptosis Modulation by HSP70
3	Cardiac Hypertrophic Response
4	Apoptosis
5	Nanoparticle triggered regulated necrosis
6	Amyotrophic lateral sclerosis (ALS)
7	Integrated Pancreatic Cancer Pathway
8	TNF alpha Signaling Pathway
9	Alzheimers Disease
10	Extrinsic Pathway for Apoptosis
11	Apoptosis Modulation and Signaling

References

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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 (NCT02221037) Study of GSK2862277 in Subjects Undergoing Oesophagectomy Surgery. U.S. National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT01759056) Evaluation of an Oral Anti-TNF Antibody in Patients With Active Ulcerative Colitis. U.S. National Institutes of Health.

REF 5

ClinicalTrials.gov (NCT01587807) A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of Inhaled GSK1995057. U.S. National Institutes of Health.

REF 6

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007694)

REF 7

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: 1870).

REF 8

Secretion of a TNFR:Fc fusion protein following pulmonary administration of pseudotyped adeno-associated virus vectors. J Virol. 2004 Nov;78(22):12355-65.

REF 9

Autoantibodies to variable heavy (VH) chain Ig sequences in humans impact the safety and clinical pharmacology of a VH domain antibody antagonist of TNF-alpha receptor 1. J Clin Immunol. 2013 Oct;33(7):1192-203.

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