Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTWN3F4)

• DTT Name: Presenilin 2 (PSEN2)
• Synonyms: STM2; STM-2; Presenilin-2; PSNL2; PS-2; E5-1; AD5; AD4; AD3LP
• Gene Name: PSEN2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Peptidase
• UniProt ID: PSN2_HUMAN
• TTD ID: T99204
• EC Number: EC 3.4.23.-
• Sequence:
  MLTFMASDSEEEVCDERTSLMSAESPTPRSCQEGRQGPEDGENTAQWRSQENEEDGEEDP
  DRYVCSGVPGRPPGLEEELTLKYGAKHVIMLFVPVTLCMIVVVATIKSVRFYTEKNGQLI
  YTPFTEDTPSVGQRLLNSVLNTLIMISVIVVMTIFLVVLYKYRCYKFIHGWLIMSSLMLL
  FLFTYIYLGEVLKTYNVAMDYPTLLLTVWNFGAVGMVCIHWKGPLVLQQAYLIMISALMA
  LVFIKYLPEWSAWVILGAISVYDLVAVLCPKGPLRMLVETAQERNEPIFPALIYSSAMVW
  TVGMAKLDPSSQGALQLPYDPEMEEDSYDSFGEPSYPEVFEPPLTGYPGEELEEEEERGV
  KLGLGDFIFYSVLVGKAAATGSGDWNTTLACFVAILIGLCLTLLLLAVFKKALPALPISI
  TFGLIFYFSTDNLVRPFMDTLASHQLYI
• Function: 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 the nuclear membrane. May function in the cytoplasmic partitioning of proteins. The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is involved in calcium homeostasis. Is a regulator of mitochondrion-endoplasmic reticulum membrane tethering and modulates calcium ions shuttling between ER and mitochondria. 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 (amyloid-beta precursor protein).
• KEGG Pathway:
  Notch signaling pathway (hsa04330)
  Neurotrophin signaling pathway (hsa04722)
  Alzheimer's disease (hsa05010)
• Reactome Pathway:
  Regulated proteolysis of p75NTR (R-HSA-193692)
  NRIF signals cell death from the nucleus (R-HSA-205043)
  Activated NOTCH1 Transmits Signal to the Nucleus (R-HSA-2122948)
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  NOTCH2 Activation and Transmission of Signal to the Nucleus (R-HSA-2979096)
  EPH-ephrin mediated repulsion of cells (R-HSA-3928665)
  Nuclear signaling by ERBB4 (R-HSA-1251985)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(S)-FLURBIPROFEN	DMF2O4T	Myalgia	FB56.2	Preregistration	[1]
R-flurbiprofen	DMFIVSR	N. A.	N. A.	Phase 2	[1]

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(2S,3R)-2-(benzyloxy)-3-methoxycyclohexanone	DMJE83O	Discovery agent	N.A.	Investigative	[2]
(5R,6S)-5,6-bis(benzyloxy)cyclohex-2-enone	DMREVX9	Discovery agent	N.A.	Investigative	[2]
(5R,6S)-6-(benzyloxy)-5-methoxycyclohex-2-enone	DMHG7MU	Discovery agent	N.A.	Investigative	[2]
1-benzoyl-2-benzyl-1,2-dihydropyridin-3(6H)-one	DMF9X2T	Discovery agent	N.A.	Investigative	[2]
1-Chloro-4-(1-phenyl-cyclohexanesulfonyl)-benzene	DM13HGN	Discovery agent	N.A.	Investigative	[3]
Drug 311383	DM5QUJV	Discovery agent	N.A.	Investigative	[4]
Drug 311440	DMOIFBK	Discovery agent	N.A.	Investigative	[4]
Drug 311951	DMXTCJ1	Discovery agent	N.A.	Investigative	[4]
Drug 311952	DM27ILS	Discovery agent	N.A.	Investigative	[4]

References

• [1] The geminal dimethyl analogue of Flurbiprofen as a novel Abeta42 inhibitor and potential Alzheimer's disease modifying agent. Bioorg Med Chem Lett. 2006 Apr 15;16(8):2219-23.
• [2] Novel gamma-secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3813-6.
• [3] Aryl sulfones: a new class of gamma-secretase inhibitors. Bioorg Med Chem Lett. 2005 May 16;15(10):2685-8.
• [4] Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase. J Med Chem. 2004 Jul 29;47(16):3931-3.