Target Information

Target General Infomation
Target ID
T99204
Former ID
TTDR00445
Target Name
Presenilin 2
Gene Name
PSEN2
Synonyms
AD3LP; AD5; E5-1; PS-2; PS2; STM-2; PSEN2
Target Type
Clinical Trial
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. May function in the cytoplasmic partitioning of proteins.
BioChemical Class
Peptidase
Target Validation
T99204
UniProt ID
P49810
EC Number
EC 3.4.23.-
Sequence
MLTFMASDSEEEVCDERTSLMSAESPTPRSCQEGRQGPEDGENTAQWRSQENEEDGEEDP
DRYVCSGVPGRPPGLEEELTLKYGAKHVIMLFVPVTLCMIVVVATIKSVRFYTEKNGQLI
YTPFTEDTPSVGQRLLNSVLNTLIMISVIVVMTIFLVVLYKYRCYKFIHGWLIMSSLMLL
FLFTYIYLGEVLKTYNVAMDYPTLLLTVWNFGAVGMVCIHWKGPLVLQQAYLIMISALMA
LVFIKYLPEWSAWVILGAISVYDLVAVLCPKGPLRMLVETAQERNEPIFPALIYSSAMVW
TVGMAKLDPSSQGALQLPYDPEMEEDSYDSFGEPSYPEVFEPPLTGYPGEELEEEEERGV
KLGLGDFIFYSVLVGKAAATGSGDWNTTLACFVAILIGLCLTLLLLAVFKKALPALPISI
TFGLIFYFSTDNLVRPFMDTLASHQLYI
Drugs and Mode of Action
Drug(s) R-flurbiprofen Drug Info Phase 2 Discovery agent [521532], [542364]
Inhibitor (2S,3R)-2-(benzyloxy)-3-methoxycyclohexanone Drug Info [528191]
(5R,6S)-5,6-bis(benzyloxy)cyclohex-2-enone Drug Info [528191]
(5R,6S)-6-(benzyloxy)-5-methoxycyclohex-2-enone Drug Info [528191]
(S)-FLURBIPROFEN Drug Info [528008]
1-benzoyl-2-benzyl-1,2-dihydropyridin-3(6H)-one Drug Info [528191]
1-Chloro-4-(1-phenyl-cyclohexanesulfonyl)-benzene Drug Info [527542]
Drug 311383 Drug Info [527143]
Drug 311440 Drug Info [527143]
Drug 311951 Drug Info [527143]
Drug 311952 Drug Info [527143]
R-flurbiprofen Drug Info [528008]
Pathways
KEGG Pathway Notch signaling pathway
Neurotrophin signaling pathway
Alzheimer&#039
s disease
PANTHER Pathway Alzheimer disease-amyloid secretase pathway
Alzheimer disease-presenilin pathway
Notch signaling pathway
Pathway Interaction Database LKB1 signaling events
Reactome Nuclear signaling by ERBB4
Regulated proteolysis of p75NTR
NRIF signals cell death from the nucleus
Activated NOTCH1 Transmits Signal to the Nucleus
Constitutive Signaling by NOTCH1 PEST Domain Mutants
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
NOTCH2 Activation and Transmission of Signal to the Nucleus
EPH-ephrin mediated repulsion of cells
WikiPathways Notch Signaling Pathway
Signaling by ERBB4
Signaling by NOTCH3
Signaling by NOTCH4
Signaling by NOTCH1
Signaling by NOTCH2
Notch Signaling Pathway
Alzheimers Disease
Signalling by NGF
References
Ref 521532ClinicalTrials.gov (NCT00045123) R-Flurbiprofen in Treating Patients With Localized Prostate Cancer at Risk of Recurrence. U.S. National Institutes of Health.
Ref 542364(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 527143J Med Chem. 2004 Jul 29;47(16):3931-3.Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase.
Ref 527542Bioorg Med Chem Lett. 2005 May 16;15(10):2685-8.Aryl sulfones: a new class of gamma-secretase inhibitors.
Ref 528008Bioorg 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 528191Bioorg 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.

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