E 2012 - CAS 870843-42-8
Catalog number:
870843-42-8
Category:
Inhibitor
Not Intended for Therapeutic Use. For research use only.
Molecular Formula:
C25H26FN3O2
Molecular Weight:
419.49
COA:
Inquire
Targets:
γ-secretase
Description:
E 2012, is a potent selective, orally bioavailable γ-secretase modulator without affecting Notch processing that can used to treat Alzheimer's Disease.
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Brife Description:
A potent selective, orally bioavailable γ-secretase modulator
Appearance:
Light yellow to yellow solid
Synonyms:
(3E)-1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]piperidin-2-one; 870843-42-8; E 2012; (E)-1-[(1S)-1-(4-FLUOROPHENYL)ETHYL]-3-[3-METHOXY-4-(4-METHYL-1H-IMIDAZOL-1-YL)BENZYLIDENE]PIPERIDIN-2-ONE; UNII-3LSD4Y5F0F; 3LSD4Y5F0F; CHEMBL1224151; E-2012; (e)-1-((1s)-1-(4-fluorophenyl)ethyl)-3-(3-methoxy-4-(4-methyl-1h-imidazol-1-yl)benzylidene)piperidin-2-one; (3E)-1-((1S)-1-(4-Fluorophenyl)ethyl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)piperidin-2-one; (3E)-1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]piperidin-2-one; GTPL7358; SCHEMBL1238634; SCHEMBL1238639; C25H26FN3O2; DTXSID30468614; PUOAETJYKQITMO-LANLRWRYSA-N; (S,E)-1-(1-(4-fluorophenyl)ethyl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)piperidin-2-one; W-5462; J-501810; I14-15434; (3E)-1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylene]piperidin-2-one; 2-Piperidinone, 1-((1S)-1-(4-fluorophenyl)ethyl)-3-((3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)methylene)-, (3E)-
Solubility:
Soluble to 10 mM in DMSO
Storage:
Store in a cool and dry place and at 0 - 4℃ for short term (days to weeks) or -33℃ for long term (months to years).
MSDS:
Inquire
Boiling Point:
649.168℃ at 760 mmHg
Density:
1.195 g/cm3
InChIKey:
PUOAETJYKQITMO-LANLRWRYSA-N
InChI:
1S/C25H26FN3O2/c1-17-15-28(16-27-17)23-11-6-19(14-24(23)31-3)13-21-5-4-12-29(25(21)30)18(2)20-7-9-22(26)10-8-20/h6-11,13-16,18H,4-5,12H2,1-3H3/b21-13+/t18-/m0/s1
Canonical SMILES:
CC1=CN(C=N1)C2=C(C=C(C=C2)C=C3CCCN(C3=O)C(C)C4=CC=C(C=C4)F)OC
1.Potent γ-secretase inhibitors/modulators interact with amyloid-β fibrils but do not inhibit fibrillation: a high-resolution NMR study.
Yesuvadian R1, Krishnamoorthy J2, Ramamoorthy A3, Bhunia A4. Biochem Biophys Res Commun. 2014 May 16;447(4):590-5. doi: 10.1016/j.bbrc.2014.04.041. Epub 2014 Apr 18.
Recently, γ-secretase modulators (GSM) have been shown to interact directly with the amyloid precursor protein (APP) and simultaneously inhibit the activity of the Presenilin domain of γ-secretase. A clear understanding of the molecular recognition pathways by which GSM can target both γ-secretase and Aβ precursor protein can lead to the development of more effective inhibitors. To examine whether this direct interaction with APP affects the downstream Aβ fibril formation, we chose to investigate three different molecules in this study: Sulindac sulfide, Semagacestat and E2012 from the class of generation I GSMs, γ-secretase inhibitors (GSI), and generation II GSM molecules, respectively. Firstly, through NMR based ligand titration, we identified that Sulindac sulfide and Semagacestat interact strongly with Aβ40 monomers, whereas E2012 does not. Secondly, using saturation transfer difference (STD) NMR experiments, we found that all three molecules bind equally well with Aβ40 fibrils.
2.Extending the PRISMA statement to equity-focused systematic reviews (PRISMA-E 2012): explanation and elaboration.
Welch V1, Petticrew M2, Petkovic J3, Moher D4, Waters E5, White H6, Tugwell P7; PRISMA-Equity Bellagio group. Int J Equity Health. 2015 Oct 8;14:92. doi: 10.1186/s12939-015-0219-2.
BACKGROUND: The promotion of health equity, the absence of avoidable and unfair differences in health outcomes, is a global imperative. Systematic reviews are an important source of evidence for health decision-makers, but have been found to lack assessments of the intervention effects on health equity. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) is a 27 item checklist intended to improve transparency and reporting of systematic reviews. We developed an equity extension for PRISMA (PRISMA-E 2012) to help systematic reviewers identify, extract, and synthesise evidence on equity in systematic reviews.
3.Novel zinc-binding site in the E2 domain regulates amyloid precursor-like protein 1 (APLP1) oligomerization.
Mayer MC1, Kaden D1, Schauenburg L1, Hancock MA2, Voigt P3, Roeser D4, Barucker C2, Than ME4, Schaefer M5, Multhaup G6. J Biol Chem. 2014 Jul 4;289(27):19019-30. doi: 10.1074/jbc.M114.570382. Epub 2014 May 22.
The amyloid precursor protein (APP) and the APP-like proteins 1 and 2 (APLP1 and APLP2) are a family of multidomain transmembrane proteins possessing homo- and heterotypic contact sites in their ectodomains. We previously reported that divalent metal ions dictate the conformation of the extracellular APP E2 domain (Dahms, S. O., Könnig, I., Roeser, D., Gührs, K.-H., Mayer, M. C., Kaden, D., Multhaup, G., and Than, M. E. (2012) J. Mol. Biol. 416, 438-452), but unresolved is the nature and functional importance of metal ion binding to APLP1 and APLP2. We found here that zinc ions bound to APP and APLP1 E2 domains and mediated their oligomerization, whereas the APLP2 E2 domain interacted more weakly with zinc possessing a less surface-exposed zinc-binding site, and stayed monomeric. Copper ions bound to E2 domains of all three proteins. Fluorescence resonance energy transfer (FRET) analyses examined the effect of metal ion binding to APP and APLPs in the cellular context in real time.
4.Are dinucleoside monophosphates relevant models for the study of DNA intrastrand cross-link lesions? The example of g[8-5m]T.
Garrec J1, Dumont E. Chem Res Toxicol. 2014 Jul 21;27(7):1133-41. doi: 10.1021/tx4004616. Epub 2014 Jun 23.
Oxidatively generated tandem lesions such as G[8-5m]T pose a potent threat to genome integrity. Direct experimental studies of the kinetics and thermodynamics of a specific lesion within DNA are very challenging, mostly due to the variety of products that can be formed in oxidative conditions. Dinucleoside monophosphates (DM) involving only the reactive nucleobases in water represent appealing alternative models on which most physical chemistry and structural techniques can be applied. However, it is not yet clear how relevant these models are. Here, we present QM/MM MD simulations of the cyclization step involved in the formation of G[8-5m]T from the guanine-thymine (GpT) DM in water, with the aim of comparing our results to our previous investigation of the same reaction in DNA ( Garrec , J. , Patel , C. , Rothlisberger , U. , and Dumont , E. ( 2012 ) J. Am. Chem. Soc. 134 , 2111 - 2119 ). We show that, despite the different levels of preorganization of the two systems, the corresponding reactions share many energetic and structural characteristics.
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CAS 870843-42-8 E 2012

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