PE859 - CAS 1402727-29-0
Category: Inhibitor
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Molecular Formula:
C28H24N4O2
Molecular Weight:
448.52
COA:
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Targets:
Microtubule/Tubulin | Tau
Description:
PE859 is a potent dual inhibitor of tau and Aβ aggregation with IC50 values of 0.66 and 1.2 μM, respectively.
Brife Description:
A potent dual inhibitor of tau and Aβ aggregation with IC50 values of 0.66 and 1.2 μM, respectively
Synonyms:
6-[(E)-2-[5-[(E)-2-[2-methoxy-4-(pyridin-2-ylmethoxy)phenyl]ethenyl]-1H-pyrazol-3-yl]ethenyl]-1H-indole; PE859; PE-859; PE 859
Solubility:
DMSO: ≥ 30 mg/mL
Storage:
Store in a cool and dry place (or refer to the Certificate of Analysis).
MSDS:
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Boiling Point:
747.7±60.0 ℃ at 760 Torr
Density:
1.312±0.06 g/cm3
InChIKey:
AMBZHNVCLPHAKA-NSJFVGFPSA-N
InChI:
1S/C28H24N4O2/c1-33-28-18-26(34-19-25-4-2-3-14-29-25)12-9-22(28)8-11-24-17-23(31-32-24)10-6-20-5-7-21-13-15-30-27(21)16-20/h2-18,30H,19H2,1H3,(H,31,32)/b10-6+,11-8+
Canonical SMILES:
COC1=C(C=CC(=C1)OCC2=CC=CC=N2)C=CC3=CC(=NN3)C=CC4=CC5=C(C=C4)C=CN5
1.PE859, a novel tau aggregation inhibitor, reduces aggregated tau and prevents onset and progression of neural dysfunction in vivo.
Okuda M;Hijikuro I;Fujita Y;Wu X;Nakayama S;Sakata Y;Noguchi Y;Ogo M;Akasofu S;Ito Y;Soeda Y;Tsuchiya N;Tanaka N;Takahashi T;Sugimoto H PLoS One. 2015 Feb 6;10(2):e0117511. doi: 10.1371/journal.pone.0117511. eCollection 2015.
In tauopathies, a neural microtubule-associated protein tau (MAPT) is abnormally aggregated and forms neurofibrillary tangle. Therefore, inhibition of the tau aggregation is one of the key approaches for the treatment of these diseases. Here, we have identified a novel tau aggregation inhibitor, PE859. An oral administration of PE859 resulted in the significant reduction of sarkosyl-insoluble aggregated tau along with the prevention of onset and progression of the motor dysfunction in JNPL3 P301L-mutated human tau transgenic mice. These results suggest that PE859 is useful for the treatment of tauopathies.
2.Design and synthesis of curcumin derivatives as tau and amyloid β dual aggregation inhibitors.
Okuda M;Hijikuro I;Fujita Y;Teruya T;Kawakami H;Takahashi T;Sugimoto H Bioorg Med Chem Lett. 2016 Oct 15;26(20):5024-5028. doi: 10.1016/j.bmcl.2016.08.092. Epub 2016 Aug 31.
Alzheimer's disease (AD) is the most common form of dementia. In an AD patient's brain, senile plaques and neurofibrillary tangles, the abnormal aggregates of amyloid β (Aβ) peptide and tau protein, are observed as the two major hallmarks of this disease. To develop a new drug for treatment of AD, we have designed and synthesized a series of curcumin derivatives and evaluated their inhibitory activities against both tau and Aβ aggregation. In this study, we describe the development of the more potent aggregation inhibitor 3-[(1E)-2-(1H-indol-6-yl)ethenyl]-5-[(1E)-2-[2-methoxy-4-(2-pyridylmethoxy) phenyl] ethenyl]-1H-pyrazole (compound 4, PE859). This compound has a better pharmacokinetic profile and pharmacological efficacy in vivo than curcumin, making it suitable as a drug for AD.
3.PE859, A Novel Curcumin Derivative, Inhibits Amyloid-β and Tau Aggregation, and Ameliorates Cognitive Dysfunction in Senescence-Accelerated Mouse Prone 8.
Okuda M;Fujita Y;Hijikuro I;Wada M;Uemura T;Kobayashi Y;Waku T;Tanaka N;Nishimoto T;Izumi Y;Kume T;Akaike A;Takahashi T;Sugimoto H J Alzheimers Dis. 2017;59(1):313-328. doi: 10.3233/JAD-161017.
Aggregation of amyloid-β (Aβ) and tau plays a crucial role in the onset and progression of Alzheimer's disease (AD). Therefore, the inhibition of Aβ and tau aggregation may represent a potential therapeutic target for AD. Herein, we designed and synthesized both Aβ and tau dual aggregation inhibitors based on the structure of curcumin and developed the novel curcumin derivative PE859. In this study, we investigated the inhibitory activity of PE859 on Aβ aggregationin vitro and the therapeutic effects of PE859 on cognitive dysfunction via dual inhibition of Aβ and tau aggregation in vivo. PE859 inhibited Aβ aggregation in vitro and protected cultured cells from Aβ-induced cytotoxicity. Furthermore, PE859 ameliorated cognitive dysfunction and reduced the amount of aggregated Aβ and tau in brains of senescence-accelerated mouse prone 8 (SAMP8). These results warrant consideration of PE859 as a candidate drug for AD.
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CAS 1402727-29-0 PE859

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