677772-84-8 Usage
Uses
Used in Pharmaceutical Industry:
MRK 560 is used as a γ-secretase inhibitor for the therapeutic strategy to counter low amyloid (β) production in Alzheimer's disease. Its oral bioavailability and potency make it a promising candidate for the treatment of this neurodegenerative disorder.
In Alzheimer's Disease Treatment:
MRK 560 is used as a therapeutic agent to reduce the levels of diethanolamine-soluble amyloid-β (1-40) (Aβ40) in the brain and cerebrospinal fluid of transgenic mouse models and rats. This reduction in Aβ40 levels can potentially slow down the progression of Alzheimer's disease and improve cognitive function.
In Neuroprotection:
MRK 560 is used to decrease brain-soluble Aβ40 and Aβ42 levels, which can help in the recovery of hippocampal long-term potentiation in the Tg2576 transgenic mouse model of Alzheimer's disease. This neuroprotective effect may contribute to the preservation of neuronal function and delay the onset of cognitive decline.
in vitro
in sh-sy5y neuroblastoma cells, mrk-560 inhibited the production of aβ(40) and aβ(42) with similar in vitro ic50 values in the range of 0.65 nm [1].
in vivo
mrk-560 was found to be able to reduce aβ in the brain and cerebrospinal fluid (csf) in the rat markedly, with ed50s of 6 and 10 mg/kg, respectively. time-course experiments demonstrated the reductions in aβ could be maintained for 24 h. comparable temporal reductions in rat brain and csf further suggested that these two pools of aβ were related. such relationship between the brain and csf aβ was maintained when mrk-560 was dosed once a day for 2 weeks. these results indicated that mrk-560 was a γ-secretase inhibitor with the ability to reduce aβ peptide in the rat brain and csf [1].
IC 50
0.65 nm for both aβ(40) and aβ(42)
references
[1] best jd,jay mt,otu f,churcher i,reilly m,morentin-gutierrez p,pattison c,harrison t,shearman ms,atack jr. in vivo characterization of abeta(40) changes in brain and cerebrospinal fluid using the novel gamma-secretase inhibitor n-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (mrk-560) in the rat. j pharmacol exp ther.2006 may;317(2):786-90.
Check Digit Verification of cas no
The CAS Registry Mumber 677772-84-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 6,7,7,7,7 and 2 respectively; the second part has 2 digits, 8 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 677772-84:
(8*6)+(7*7)+(6*7)+(5*7)+(4*7)+(3*2)+(2*8)+(1*4)=228
228 % 10 = 8
So 677772-84-8 is a valid CAS Registry Number.
677772-84-8Relevant academic research and scientific papers
Sulphonamido-Substituted Cyclohexyl Sulphones for Treatment of Cancer
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, (2009/09/07)
Compounds of formula (I) are disclosed for treatment of cancer.
4-Substituted cyclohexyl sulfones as potent, orally active γ-secretase inhibitors
Churcher, Ian,Beher, Dirk,Best, Jonathan D.,Castro, Jose L.,Clarke, Earl E.,Gentry, Amy,Harrison, Timothy,Hitzel, Laure,Kay, Euan,Kerrad, Sonia,Lewis, Huw D.,Morentin-Gutierrez, Pablo,Mortishire-Smith, Russell,Oakley, Paul J.,Reilly, Michael,Shaw, Duncan E.,Shearman, Mark S.,Teall, Martin R.,Williams, Susie,Wrigley, Jonathan D.J.
, p. 280 - 284 (2007/10/03)
The protease γ-secretase plays a pivotal role in the synthesis of pathogenic amyloid-β in Alzheimer's disease (AD). Here, we report a further extension to a series of cyclohexyl sulfone-based γ-secretase inhibitors which has allowed the preparation of hig
CYCLOHEXYL SULPHONES AS GAMMA-SECRETASE INHIBITORS
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Page 24, (2010/02/06)
Compounds of formula (I) inhibit the processing of APP by gamma-secretase, and hence are useful in treating or preventing Alzheimer's disease.
