Target Information
| Target General Information | Top | |||||
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| Target ID |
T07400
(Former ID: TTDR00745)
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| Target Name |
Advanced glycosylation end product receptor (AGER)
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| Synonyms |
Receptor foradvanced glycosylation end products; RAGESEC; RAGE; AGER
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| Gene Name |
AGER
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 4 Target-related Diseases | + | ||||
| 1 | Alzheimer disease [ICD-11: 8A20] | |||||
| 2 | Chronic kidney disease [ICD-11: GB61] | |||||
| 3 | Dementia [ICD-11: 6D80-6D8Z] | |||||
| 4 | Hypotension [ICD-11: BA20-BA21] | |||||
| 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.
Click to Show/Hide
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| BioChemical Class |
Immunoglobulin
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| UniProt ID | ||||||
| Sequence |
MAAGTAVGAWVLVLSLWGAVVGAQNITARIGEPLVLKCKGAPKKPPQRLEWKLNTGRTEA
WKVLSPQGGGPWDSVARVLPNGSLFLPAVGIQDEGIFRCQAMNRNGKETKSNYRVRVYQI PGKPEIVDSASELTAGVPNKVGTCVSEGSYPAGTLSWHLDGKPLVPNEKGVSVKEQTRRH PETGLFTLQSELMVTPARGGDPRPTFSCSFSPGLPRHRALRTAPIQPRVWEPVPLEEVQL VVEPEGGAVAPGGTVTLTCEVPAQPSPQIHWMKDGVPLPLPPSPVLILPEIGPQDQGTYS CVATHSSHGPQESRAVSISIIEPGEEGPTAGSVGGSGLGTLALALGILGGLGTAALLIGV ILWQRRQRRGEERKAPENQEEEEERAELNQSEEPEAGESSTGGP Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T59Y35 | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 5 Clinical Trial Drugs | + | ||||
| 1 | PF-4494700 | Drug Info | Phase 3 | Dementia | [2], [3] | |
| 2 | Pyridoxamine | Drug Info | Phase 3 | Diabetic nephropathy | [4] | |
| 3 | Alagebrium chloride | Drug Info | Phase 2/3 | Hypotension | [5] | |
| 4 | TTP-448 | Drug Info | Phase 2 | Alzheimer disease | [6] | |
| 5 | TTP-4000 | Drug Info | Phase 1 | Alzheimer disease | [7] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | PF-4494700 | Drug Info | [1] | |||
| Inhibitor | [+] 2 Inhibitor drugs | + | ||||
| 1 | Pyridoxamine | Drug Info | [8], [9] | |||
| 2 | TTP-4000 | Drug Info | [12] | |||
| Breaker | [+] 1 Breaker drugs | + | ||||
| 1 | Alagebrium chloride | Drug Info | [10], [11] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | TTP-448 | Drug Info | [1] | |||
| 2 | DBT-066 | Drug Info | [13] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | amb2 Integrin signaling | |||||
| Reactome | [+] 5 Reactome Pathways | + | ||||
| 1 | RIP-mediated NFkB activation via ZBP1 | |||||
| 2 | DEx/H-box helicases activate type I IFN and inflammatory cytokines production | |||||
| 3 | TAK1 activates NFkB by phosphorylation and activation of IKKs complex | |||||
| 4 | Advanced glycosylation endproduct receptor signaling | |||||
| 5 | TRAF6 mediated NF-kB activation | |||||
| WikiPathways | [+] 7 WikiPathways | + | ||||
| 1 | NRF2 pathway | |||||
| 2 | Nuclear Receptors Meta-Pathway | |||||
| 3 | Cytosolic sensors of pathogen-associated DNA | |||||
| 4 | TAK1 activates NFkB by phosphorylation and activation of IKKs complex | |||||
| 5 | AGE/RAGE pathway | |||||
| 6 | RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways | |||||
| 7 | Advanced glycosylation endproduct receptor signaling | |||||
| References | Top | |||||
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| REF 1 | Receptor for advanced glycation endproduct modulators: a new therapeutic target in Alzheimer's disease. Expert Opin Investig Drugs. 2015 Mar;24(3):393-9. | |||||
| REF 2 | 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. (Ligand id: 8317). | |||||
| REF 3 | ClinicalTrials.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 4 | ClinicalTrials.gov (NCT02156843) Pyridorin in Diabetic Nephropathy. U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT01417663) Effects of Exercise Training and AGE-crosslink Breaker on Cardiovascular Structure and Function. U.S. National Institutes of Health. | |||||
| REF 6 | Biopharmaceutical Research Companies are Developing Nearly 100 Medicines for Alzheimer's Disease and Other Dementias. Pharmaceutical Research and Manufacturers of America report. 2012. | |||||
| REF 7 | ClinicalTrials.gov (NCT01548430) A Safety Study of TTP4000 in Subjects With Alzheimer's Disease. U.S. National Institutes of Health. | |||||
| REF 8 | Pyridoxamine, 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 9 | The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. Diabetes. 2002 Sep;51(9):2826-32. | |||||
| REF 10 | Effect 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 11 | Alagebrium reduces glomerular fibrogenesis and inflammation beyond preventing RAGE activation in diabetic apolipoprotein E knockout mice. Diabetes. 2012 Aug;61(8):2105-13. | |||||
| REF 12 | Receptor for advanced glycation end products: its role in Alzheimer's disease and other neurological diseases. Future Neurol. 2009; 4(2): 167-177. | |||||
| REF 13 | 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: 2843). | |||||
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