gamma-secretase modulator 5

gamma-secretase modulator 5 (compound 22d) is a brain-penetrant gamma-secretase modulator (GSMs) that inhibits the production of the aggregated amyloid β-peptide Aβ42 with an IC50 value of 60 nM. gamma-secretase modulator 5 can be used in the study of Alzheimer's disease[1].

Research Areas >> Neurological Disease

Aβ38:305 nM (EC50)

Aβ40:104 nM (IC50)

Aβ42:60 nM (IC50)

gamma-secretase modulator 5 (compound 22d) (1-10 μM, 24 h) does not affect the function of the APP751 enzyme and not inhibit Notching processing in H4 human neuroglioma cells over-expressing human APP751[1]. gamma-secretase modulator 5 (compound 22d) acts on Aβ38 with the EC50 value of 305 nM and acts on Aβ40 with the IC50 value of 104 nM[1].

The pharmacokinetic parameters of gamma-secretase modulator 5 (compound 22d) in male CD-1 mice[1]. Parameters IV PO Dose (mg/kg) 1 5 Cmax (ng/mL) 824 705 Tmax (h) 0.083 0.25 t1/2 (h) 0.5 - AUClast (ng•h/mL) 443 1089 AUCinf (ng•h/mL) 463 1243 Cl (mL/h/kg) 2159 - Vss (mL/kg) 1413 - F (%) 100 53.7

[1]. Kevin D Rynearson, et al. Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators. Bioorg Med Chem. 2020 Nov 15;28(22):115734.