Target Information
| Target General Information | Top | |||||
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| Target ID |
T99204
(Former ID: TTDR00445)
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| Target Name |
Presenilin 2 (PSEN2)
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| Synonyms |
STM2; STM-2; Presenilin-2; PSNL2; PS-2; E5-1; AD5; AD4; AD3LP
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| Gene Name |
PSEN2
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Osteoarthritis [ICD-11: FA00-FA05] | |||||
| 2 | Shoulder lesion [ICD-11: FB53] | |||||
| 3 | Soft tissue disorder [ICD-11: FB56] | |||||
| 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).
Click to Show/Hide
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.23.-
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| Sequence |
MLTFMASDSEEEVCDERTSLMSAESPTPRSCQEGRQGPEDGENTAQWRSQENEEDGEEDP
DRYVCSGVPGRPPGLEEELTLKYGAKHVIMLFVPVTLCMIVVVATIKSVRFYTEKNGQLI YTPFTEDTPSVGQRLLNSVLNTLIMISVIVVMTIFLVVLYKYRCYKFIHGWLIMSSLMLL FLFTYIYLGEVLKTYNVAMDYPTLLLTVWNFGAVGMVCIHWKGPLVLQQAYLIMISALMA LVFIKYLPEWSAWVILGAISVYDLVAVLCPKGPLRMLVETAQERNEPIFPALIYSSAMVW TVGMAKLDPSSQGALQLPYDPEMEEDSYDSFGEPSYPEVFEPPLTGYPGEELEEEEERGV KLGLGDFIFYSVLVGKAAATGSGDWNTTLACFVAILIGLCLTLLLLAVFKKALPALPISI TFGLIFYFSTDNLVRPFMDTLASHQLYI Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | (S)-FLURBIPROFEN | Drug Info | Preregistration | Myalgia | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 11 Inhibitor drugs | + | ||||
| 1 | (S)-FLURBIPROFEN | Drug Info | [1] | |||
| 2 | R-flurbiprofen | Drug Info | [1] | |||
| 3 | (2S,3R)-2-(benzyloxy)-3-methoxycyclohexanone | Drug Info | [3] | |||
| 4 | (5R,6S)-5,6-bis(benzyloxy)cyclohex-2-enone | Drug Info | [3] | |||
| 5 | (5R,6S)-6-(benzyloxy)-5-methoxycyclohex-2-enone | Drug Info | [3] | |||
| 6 | 1-benzoyl-2-benzyl-1,2-dihydropyridin-3(6H)-one | Drug Info | [3] | |||
| 7 | 1-Chloro-4-(1-phenyl-cyclohexanesulfonyl)-benzene | Drug Info | [4] | |||
| 8 | Drug 311383 | Drug Info | [5] | |||
| 9 | Drug 311440 | Drug Info | [5] | |||
| 10 | Drug 311951 | Drug Info | [5] | |||
| 11 | Drug 311952 | Drug Info | [5] | |||
| 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 Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025057) | |||||
| REF 3 | 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. | |||||
| REF 4 | Aryl sulfones: a new class of gamma-secretase inhibitors. Bioorg Med Chem Lett. 2005 May 16;15(10):2685-8. | |||||
| REF 5 | Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase. J Med Chem. 2004 Jul 29;47(16):3931-3. | |||||
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