Target Information
Target General Infomation | |||||
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Target ID |
T93105
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Former ID |
TTDR00444
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Target Name |
Presenilin 1
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Gene Name |
PSEN1
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Synonyms |
PS-1; PS1; S182 protein; PSEN1
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Target Type |
Clinical Trial
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Function |
Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to thenuclear membrane. Stimulates cell-cell adhesion though its association with the E-cadherin/catenin complex. Under conditions of apoptosis or calcium influx, cleaves E-cadherin promoting the disassembly of the E-cadherin/catenin complex and increasing the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling. May also play a role in hematopoiesis.
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BioChemical Class |
Peptidase
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Target Validation |
T93105
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UniProt ID | |||||
EC Number |
EC 3.4.23.-
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Sequence |
MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSR
QVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTE DTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFI YLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKY LPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAE GDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAA VQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCL TLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI |
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Drugs and Mode of Action | |||||
Drug(s) | R-flurbiprofen | Drug Info | Phase 2 | Discovery agent | [1], [2] |
Inhibitor | (2S,3R)-2-(benzyloxy)-3-methoxycyclohexanone | Drug Info | [3] | ||
(5R,6S)-5,6-bis(benzyloxy)cyclohex-2-enone | Drug Info | [3] | |||
(5R,6S)-6-(benzyloxy)-5-methoxycyclohex-2-enone | Drug Info | [3] | |||
(S)-FLURBIPROFEN | Drug Info | [4] | |||
1-benzoyl-2-benzyl-1,2-dihydropyridin-3(6H)-one | Drug Info | [3] | |||
1-Chloro-4-(1-phenyl-cyclohexanesulfonyl)-benzene | Drug Info | [5] | |||
Drug 311383 | Drug Info | [6] | |||
Drug 311440 | Drug Info | [6] | |||
Drug 311951 | Drug Info | [6] | |||
Drug 311952 | Drug Info | [6] | |||
R-flurbiprofen | Drug Info | [4] | |||
Pathways | |||||
KEGG Pathway | Wnt signaling pathway | ||||
Notch signaling pathway | |||||
Neurotrophin signaling pathway | |||||
Alzheimer' | |||||
s disease | |||||
NetPath Pathway | Notch Signaling Pathway | ||||
PANTHER Pathway | Alzheimer disease-amyloid secretase pathway | ||||
Alzheimer disease-presenilin pathway | |||||
Notch signaling pathway | |||||
Pathway Interaction Database | Notch signaling pathway | ||||
Presenilin action in Notch and Wnt signaling | |||||
p75(NTR)-mediated signaling | |||||
Syndecan-3-mediated signaling events | |||||
Reactome | Degradation of the extracellular matrix | ||||
WikiPathways | Notch Signaling Pathway | ||||
Notch Signaling Pathway | |||||
Alzheimers Disease | |||||
References | |||||
REF 1 | ClinicalTrials.gov (NCT00045123) R-Flurbiprofen in Treating Patients With Localized Prostate Cancer at Risk of Recurrence. U.S. National Institutes of Health. | ||||
REF 2 | (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: 7340). | ||||
REF 3 | Bioorg Med Chem Lett. 2006 Jul 15;16(14):3813-6. Epub 2006 May 8.Novel gamma-secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates. | ||||
REF 4 | Bioorg Med Chem Lett. 2006 Apr 15;16(8):2219-23. Epub 2006 Feb 7.The geminal dimethyl analogue of Flurbiprofen as a novel Abeta42 inhibitor and potential Alzheimer's disease modifying agent. | ||||
REF 5 | Bioorg Med Chem Lett. 2005 May 16;15(10):2685-8.Aryl sulfones: a new class of gamma-secretase inhibitors. | ||||
REF 6 | J Med Chem. 2004 Jul 29;47(16):3931-3.Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase. |
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