Target Information

Target General Infomation
Target ID
T07400
Former ID
TTDR00745
Target Name
Advanced glycosylation end product-specific receptor
Gene Name
AGER
Synonyms
RAGE; RAGESEC; Receptor foradvanced glycosylation end products; AGER
Target Type
Clinical Trial
Disease Alzheimer disease [ICD9: 331; ICD10: G30]
Dementia [ICD9: 290-294; ICD10: F01-F07]
Diabetic kidney disease; Diabetic nephropathy [ICD9:250.4; ICD10: E11.22, E11.21]
Hypotension [ICD9: 458, 796.3; ICD10: I95]
Function
Mediates interactions of advanced glycosylation end products (age). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Receptor for amyloid beta peptide.
BioChemical Class
Immunoglobulin
UniProt ID
Q15109
Sequence
MAAGTAVGAWVLVLSLWGAVVGAQNITARIGEPLVLKCKGAPKKPPQRLEWKLNTGRTEA
WKVLSPQGGGPWDSVARVLPNGSLFLPAVGIQDEGIFRCQAMNRNGKETKSNYRVRVYQI
PGKPEIVDSASELTAGVPNKVGTCVSEGSYPAGTLSWHLDGKPLVPNEKGVSVKEQTRRH
PETGLFTLQSELMVTPARGGDPRPTFSCSFSPGLPRHRALRTAPIQPRVWEPVPLEEVQL
VVEPEGGAVAPGGTVTLTCEVPAQPSPQIHWMKDGVPLPLPPSPVLILPEIGPQDQGTYS
CVATHSSHGPQESRAVSISIIEPGEEGPTAGSVGGSGLGTLALALGILGGLGTAALLIGV
ILWQRRQRRGEERKAPENQEEEEERAELNQSEEPEAGESSTGGP
Drugs and Mode of Action
Drug(s) PF-4494700 Drug Info Phase 3 Dementia [524669], [543068]
Pyridoxamine Drug Info Phase 3 Diabetic kidney disease; Diabetic nephropathy [524788]
Alagebrium chloride Drug Info Phase 2/3 Hypotension [523591]
TTP-448 Drug Info Phase 2 Alzheimer disease [550058]
TTP-4000 Drug Info Phase 1 Alzheimer disease [523827]
Breaker Alagebrium chloride Drug Info [530684], [531941]
Modulator DBT-066 Drug Info [543730]
TTP-448 Drug Info [533109]
Antagonist PF-4494700 Drug Info [533109]
Inhibitor Pyridoxamine Drug Info [526411], [530891]
TTP-4000 Drug Info [544085]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
Pathway Interaction Database amb2 Integrin signaling
Reactome RIP-mediated NFkB activation via ZBP1
DEx/H-box helicases activate type I IFN and inflammatory cytokines production
TAK1 activates NFkB by phosphorylation and activation of IKKs complex
Advanced glycosylation endproduct receptor signaling
TRAF6 mediated NF-kB activation
WikiPathways NRF2 pathway
Nuclear Receptors Meta-Pathway
Cytosolic sensors of pathogen-associated DNA
TAK1 activates NFkB by phosphorylation and activation of IKKs complex
AGE/RAGE pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
Advanced glycosylation endproduct receptor signaling
References
Ref 523591ClinicalTrials.gov (NCT01417663) Effects of Exercise Training and AGE-crosslink Breaker on Cardiovascular Structure and Function. U.S. National Institutes of Health.
Ref 523827ClinicalTrials.gov (NCT01548430) A Safety Study of TTP4000 in Subjects With Alzheimer's Disease. U.S. National Institutes of Health.
Ref 524669ClinicalTrials.gov (NCT02080364) Evaluation of the Efficacy and Safety of Azeliragon (TTP488) in Patients With Mild Alzheimer's Disease. U.S. National Institutes of Health.
Ref 524788ClinicalTrials.gov (NCT02156843) Pyridorin in Diabetic Nephropathy. U.S. National Institutes of Health.
Ref 543068(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. (Ligand id: 8317).
Ref 550058Biopharmaceutical Research Companies are Developing Nearly 100 Medicines for Alzheimer's Disease and Other Dementias. Pharmaceutical Research and Manufacturers of America report. 2012.
Ref 526411The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. Diabetes. 2002 Sep;51(9):2826-32.
Ref 530684Effect of the age cross-link breaker alagebrium on anterior segment physiology, morphology, and ocular age and rage. Trans Am Ophthalmol Soc. 2009 Dec;107:146-58.
Ref 530891Pyridoxamine, an inhibitor of advanced glycation end product (AGE) formation ameliorates insulin resistance in obese, type 2 diabetic mice. Protein Pept Lett. 2010 Sep;17(9):1177-81.
Ref 531941Alagebrium reduces glomerular fibrogenesis and inflammation beyond preventing RAGE activation in diabetic apolipoprotein E knockout mice. Diabetes. 2012 Aug;61(8):2105-13.
Ref 533109Receptor for advanced glycation endproduct modulators: a new therapeutic target in Alzheimer's disease. Expert Opin Investig Drugs. 2015 Mar;24(3):393-9.
Ref 543730(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: 2843).
Ref 544085Receptor for advanced glycation end products: its role in Alzheimer's disease and other neurological diseases. Future Neurol. 2009; 4(2): 167-177.

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