Target Information

Target General Infomation
Target ID
T86552
Former ID
TTDNC00502
Target Name
Tumour necrosis factor receptor-1 (TNFR1)
Gene Name
TNFRSF1A
Synonyms
CD120a; TBPI; TNF-R1; TNF-RI; TNFR-I; Tumor necrosis factor receptor 1; Tumor necrosis factor receptor type I; Tumor necrosis factor-binding protein 1; TNFRSF1A
Target Type
Clinical Trial
Disease Adult respiratory distress syndrome [ICD9: 518.5, 518.82; ICD10: J80]
Acute liver failure [ICD10: K72]
Arthritis [ICD9: 710-719; ICD10: M00-M25]
Acute lung injury [ICD9: 518; ICD10: J80]
Autoimmune diabetes [ICD10: E08-E13]
Alopecia [ICD9: 704.09; ICD10: L65.9]
Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47]
Glioblastoma multiforme [ICD9: 191; ICD10: C71]
Inflammatory bowel disease [ICD9: 555, 556; ICD10: K50, K51]
Multiple scierosis [ICD9: 340; ICD10: G35]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Function
Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. 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. .
BioChemical Class
Cytokine receptor
UniProt ID
P19438
Sequence
MGLSTVPDLLLPLVLLELLVGIYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCT
KCHKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVD
RDTVCGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECV
SCSNCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVIFFGLCLLSLLFIGLMYRYQRWK
SKLYSIVCGKSTPEKEGELEGTTTKPLAPNPSFSPTPGFTPTLGFSPVPSSTFTSSSTYT
PGDCPNFAAPRREVAPPYQGADPILATALASDPIPNPLQKWEDSAHKPQSLDTDDPATLY
AVVENVPPLRWKEFVRRLGLSDHEIDRLELQNGRCLREAQYSMLATWRRRTPRREATLEL
LGRVLRDMDLLGCLEDIEEALCGPAALPPAPSLLR
Drugs and Mode of Action
Drug(s) Drug 2862277 Drug Info Phase 2 Acute lung injury [524882]
VB-111 Drug Info Phase 2 Glioblastoma multiforme [531640]
AVX-470 Drug Info Phase 1 Inflammatory bowel disease [524174]
GSK1995057 Drug Info Phase 1 Adult respiratory distress syndrome [523888]
Anti-IFN gamma Drug Info Terminated Alopecia [546358]
Modulator ALF-421 Drug Info [527270]
NM-2014 Drug Info [543512]
Recombinant human TNF receptor Drug Info [527270]
TNF-targeting small molecule therapeutic, oral, inflammation/autoimmune disease Drug Info [527270]
TNFcept Drug Info [527270]
TNFR1 NAM Drug Info [543512]
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
NF-kappa B signaling pathway
Sphingolipid signaling pathway
Apoptosis
Osteoclast differentiation
TNF signaling pathway
Adipocytokine signaling pathway
Non-alcoholic fatty liver disease (NAFLD)
Alzheimer&#039
s disease
Amyotrophic lateral sclerosis (ALS)
Chagas disease (American trypanosomiasis)
Toxoplasmosis
Tuberculosis
Hepatitis C
Influenza A
HTLV-I infection
Herpes simplex infection
NetPath Pathway TGF_beta_Receptor Signaling Pathway
TCR Signaling Pathway
PANTHER Pathway Apoptosis signaling pathway
Pathway Interaction Database Canonical NF-kappaB pathway
Signaling events mediated by HDAC Class I
TNF receptor signaling pathway
Ceramide signaling pathway
Negative effector of Fas and TNF-alpha
Caspase Cascade in Apoptosis
Reactome TNFR1-induced proapoptotic signaling
Regulation of TNFR1 signaling
TNFR1-induced NFkappaB signaling pathway
TNFR1-mediated ceramide production
TNFs bind their physiological receptors
TNF signaling
WikiPathways Inflammatory Response Pathway
Apoptosis Modulation by HSP70
Cardiac Hypertrophic Response
Apoptosis
Nanoparticle triggered regulated necrosis
Amyotrophic lateral sclerosis (ALS)
Integrated Pancreatic Cancer Pathway
TNF alpha Signaling Pathway
Alzheimers Disease
Extrinsic Pathway for Apoptosis
Apoptosis Modulation and Signaling
References
Ref 523888ClinicalTrials.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 524174ClinicalTrials.gov (NCT01759056) Evaluation of an Oral Anti-TNF Antibody in Patients With Active Ulcerative Colitis. U.S. National Institutes of Health.
Ref 524882ClinicalTrials.gov (NCT02221037) Study of GSK2862277 in Subjects Undergoing Oesophagectomy Surgery. U.S. National Institutes of Health.
Ref 531640VB-111 for cancer. Expert Opin Biol Ther. 2011 Dec;11(12):1669-76.
Ref 546358Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007694)
Ref 527270Secretion of a TNFR:Fc fusion protein following pulmonary administration of pseudotyped adeno-associated virus vectors. J Virol. 2004 Nov;78(22):12355-65.
Ref 532420Autoantibodies 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.
Ref 543512(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).

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