Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTMO9HF)

• DTT Name: Advanced glycosylation end product receptor (AGER)
• Synonyms: Receptor foradvanced glycosylation end products; RAGESEC; RAGE; AGER
• Gene Name: AGER
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Alzheimer disease [ICD-11: 8A20]
  Chronic kidney disease [ICD-11: GB61]
  Dementia [ICD-11: 6D80-6D8Z]
  Hypotension [ICD-11: BA20-BA21]
• BioChemical Class: Immunoglobulin
• UniProt ID: RAGE_HUMAN
• TTD ID: T07400
• Sequence:
  MAAGTAVGAWVLVLSLWGAVVGAQNITARIGEPLVLKCKGAPKKPPQRLEWKLNTGRTEA
  WKVLSPQGGGPWDSVARVLPNGSLFLPAVGIQDEGIFRCQAMNRNGKETKSNYRVRVYQI
  PGKPEIVDSASELTAGVPNKVGTCVSEGSYPAGTLSWHLDGKPLVPNEKGVSVKEQTRRH
  PETGLFTLQSELMVTPARGGDPRPTFSCSFSPGLPRHRALRTAPIQPRVWEPVPLEEVQL
  VVEPEGGAVAPGGTVTLTCEVPAQPSPQIHWMKDGVPLPLPPSPVLILPEIGPQDQGTYS
  CVATHSSHGPQESRAVSISIIEPGEEGPTAGSVGGSGLGTLALALGILGGLGTAALLIGV
  ILWQRRQRRGEERKAPENQEEEEERAELNQSEEPEAGESSTGGP
• 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.
• KEGG Pathway:
  Neutrophil extracellular trap formation (hsa04613)
  AGE-RAGE signaling pathway in diabetic complications (hsa04933)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Diabetic cardiomyopathy (hsa05415)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  DEx/H-box helicases activate type I IFN and inflammatory cytokines production (R-HSA-3134963)
  TAK1 activates NFkB by phosphorylation and activation of IKKs complex (R-HSA-445989)
  Advanced glycosylation endproduct receptor signaling (R-HSA-879415)
  TRAF6 mediated NF-kB activation (R-HSA-933542)
  RIP-mediated NFkB activation via ZBP1 (R-HSA-1810476)

Molecular Interaction Atlas (MIA) of This DTT

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-4494700	DMJ7IKW	Alzheimer disease	8A20	Phase 3	[1]
Pyridoxamine	DMVDCGZ	Diabetic kidney disease	GB61.Z	Phase 3	[2], [3]
Alagebrium chloride	DMD741P	Hypotension	BA20-BA21	Phase 2/3	[4], [5]
TTP-448	DMR37X8	Alzheimer disease	8A20	Phase 2	[1]
TTP-4000	DMCG01R	Alzheimer disease	8A20	Phase 1	[6]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DBT-066	DMFYCQ1	Dementia	6D80-6D86	Investigative	[7]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	7.92E-01	6.77E-03	0.04

References

• [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.
• [2] 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.
• [3] The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. Diabetes. 2002 Sep;51(9):2826-32.
• [4] 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.
• [5] Alagebrium reduces glomerular fibrogenesis and inflammation beyond preventing RAGE activation in diabetic apolipoprotein E knockout mice. Diabetes. 2012 Aug;61(8):2105-13.
• [6] Receptor for advanced glycation end products: its role in Alzheimer's disease and other neurological diseases. Future Neurol. 2009; 4(2): 167-177.
• [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: 2843).