gamma-Secretase Modulators

Short Summary : Amyloid-β production inhibitor

Category : Neuroscience|Amyloid β

Purity : 0.98

CAS Number : 937812-80-1

Formula : C26H24F3N3O3

Molecular Weight : 483.49

SMILE : CC1=CN(C=N1)C2=C(C=C(C=C2)C=C3CCC4COCC(N4C3=O)C5=CC(=C(C(=C5)F)F)F)OC

Solubility : Soluble in DMSO

Storage : Store at -20°C

Description : Oxadiazine is a potent modulator of γ-secretase with Aβ42 IC50 value of 11 nM and Aβtotal/ Aβ42 value of 1170.[1]γ-Secretase is one of intramenbrane-cleaving aspartyl protease which cleaves many type-I membrane proteins and many of them have important biological functions.γ-secretase is responsible for the generation Aβfrom the amyloid precusor protein.γ-Secretase has been considered as an important drug target for Alzheimer’s disease.γ-Secertase also is responsible for Notch processing which is related to cancer such as leukemia.Oxadiazine is one analogues of BMS-869780 which is anotherγ-secretase modulator. It showed a four folds separation between the IC 50 of Aβ42 and Aβ40 H4-APPsw cells which overexpress APP protein. It also increase Aβ37 and Aβ38 levels whereas decrease Aβ42 and Aβ40 level. It also has little effect on APP-CTFα and no effect on APP-CTFβ and notch processing. It can significantly decrease Aβ42 and Aβ40 level in rat brain and plasma.[1, 2]References: [1]. Huang X, Zhou W, Liu X, Li H, Sun G, Mandal M, Vicarel M, Zhu X, Bennett C, McCraken T et al: Synthesis and SAR Studies of Fused Oxadiazines as gamma-Secretase Modulators for Treatment of Alzheimer’s Disease. ACS Med Chem Lett, 3(11):931-935.[2]. Toyn JH, Thompson LA, Lentz KA, Meredith JE, Jr., Burton CR, Sankaranararyanan S, Guss V, Hall T, Iben LG, Krause CM et al: Identification and Preclinical Pharmacology of the gamma-Secretase Modulator BMS-869780. Int J Alzheimers Dis, 2014:431858.

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