Semagacestat

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的 γ-分泌酶抑制剂，可抑制 β-淀粉样蛋白 Aβ42、Aβ38 和 Aβ40，IC50 分别为 10.9、12 和 12.1 nM。

A potent γ-secretase inhibitor that inhibits β-amyloid Aβ42, Aβ38 and Aβ40 with IC50 of 10.9, 12 and 12.1 nM, respectively; reduces the secretion of Aβ42, Aβ40, and Aβ38 in cells and increases β-CTF in cell lysates, also inhibits Notch signaling with IC50 of 14.1 nM; increases intracellular byproduct peptides, produced along with Aβ through serial γ-cleavage of βAPP, as well as intracellular long Aβ species, in cell-based and in vivo studies of AD model mice; a pseudo-inhibitor of γ-secretase.Alzheimer's Disease Phase 3 Discontinued(In Vitro):Semagacestat (LY450139) reduces the secretion of Aβ42, Aβ40, and Aβ38 in 96-well-cultured media and increases β-CTF in cell lysates as expected, although this increase is unexpectedly attenuated at high concentrations.In cortical neurons (CTX), Semagacestat (LY450139) causes a concentration-dependent decrease in Aβ40 secreted into the medium with IC50 value 111 nM for Semagacestat. Semagacestat causes a concentration-dependent decrease in Aβ40 and Aβ42 secreted into the medium with an IC50 value of 126 and 130 nM, respectively.Semagacestat (3 Μm; for 4 days) exhibits no significant cell toxicity in Huh7 cells.

Semagacestat (LY450139) reduces the secretion of Aβ42, Aβ40, and Aβ38 in 96-well-cultured media and increases β-CTF in cell lysates as expected, although this increase is unexpectedly attenuated at high concentrations. In cortical neurons (CTX), Semagacestat (LY450139) causes a concentration-dependent decrease in Aβ40 secreted into the medium with IC50 value 111 nM for Semagacestat. Semagacestat causes a concentration-dependent decrease in Aβ40 and Aβ42 secreted into the medium with an IC50 value of 126 and 130 nM, respectively. Semagacestat (3 Μm; for 4 days) exhibits no significant cell toxicity in Huh7 cells.

Semagacestat (LY450139) is found to decrease both Aβ42 and Aβ40 at 10 mg/kg (22-23% reduction;p<0.01) and increase β-CTF at 0.3-10 mg/kg in a dose-dependent manner (15-162% elevation; p<0.01 at 1-10 mg/kg). The γ-secretase inhibitor, Semagacestat (LY450139), a highly potent low molecular weight compound, significantly reduces β-amyloid (Aβ) levels in cell cultures permanently over-expressing APP and in both wildtype and transgenic APP-expressing mice. Three hours following p.o. dosing of 30 mg/kg Semagacestat levels of Aβ40 are reduced by 43% (unpaired t-test, p=0.002) in the brains of wildtype C57BL/6 mice compare with vehicle treated controls. Subcutaneous administration of Semagacestat (30 mg/kg) transiently decreases the amounts of Aβ40 in the dialysate with a maximum reduction in Aβ40 levels of 80% at 3 h post-dosing (p<0.001).

LY450139 | LY-450139

Wnt/Notch/Hedgehog

γ-secretase

Notch|γsecretase(Aβ38)|γsecretase(Aβ40)|γsecretase(Aβ42)

Neurological Disease

Alzheimer Disease

425386-60-3

361.4354

C19H27N3O4

>98% (HPLC)

10 mM in DMSO

CC(C)[C@H](O)C(N[C@@H](C)C(N[C@@H]1C(N(C)CCC2=CC=CC=C12)=O)=O)=O

Butanamide, 2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-oxo-2-[[(1S)-2,3,4,5-tetrahydro-3-methyl-2-oxo-1H-3-benzazepin-1-yl]amino]ethyl]-, (2S)-

(-20℃)

With Ice Pack

≥ 2 years