NGP555 - γ-secretase Modulator - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemENGP555Cat. No.: HY-108714CAS No.: 1304630-27-0分式: CHFNS分量: 406.52作靶点: -secretase作通路: Neuronal Signaling; Stem Cell/Wnt储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 42.9 mg/mL (105.53 mM;

2、Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.4599 mL 12.2995 mL 24.5990 mL5 mM 0.4920 mL 2.4599 mL 4.9198 mL10 mM 0.2460 mL 1.2300 mL 2.4599 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 NGP555个 -分泌酶 (-secretase) 调节剂。IC50 & Target -secretase

3、 1体外研究 NGP555 potently lowers A42 in cell cultures (9 nM) while increasing shorter forms of A 1.体内研究NGP555 significantly lowers A42 in the cerebrospinal fluid (CSF) at time points from 8 to10 hours post1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEdose, panel B shows that reduction of A cerebrosp

4、inal fluid (CSF) levels is significant at 3.75 mg/kg ofNGP555 and above, and panel C shows an increase in A38 levels at 15 mg/kg of NGP555 and above.When combining the reduction of A42 with an increase in A38, NGP555 is effective at raising CSF A38/42 ratio at 1.87 mg/kg and above (panel D). NGP555-

5、treated Tg mice show a significant protection fromdecline in performance with 65% less decline (P 1.PROTOCOLCell Assay 1 SH-SY5Y-APP cells, Tg2576 mixed brain cultures, or C57 mixed brain cultures are treated with variousconcentrations of NGP555 in triplicate wells, for 18 hours. Media is collected

6、and analyzed for A peptidesusing triplex ELISA (A38 and A42) 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal For CSF studies, Normal Sprague-Dawley male rats (250 to 300 g) are administered NGP555 in 80% PEGAdministration 1 orally or vehicle on

7、ly, n=10/group. Rats are dosed once-daily for a single-dose or 14 days of dosing. After thefinal dose, cerebrospinal fluid (CSF) samples are either collected at varying time points or a single time pointpost-last dose. Rats are deeply anesthetized with isoflurane, and CSF is collected from the ciste

8、rna magna.Samples are tested for A level. For Y-maze study, transgenic mice (Tg2576 line expressing the APP-Swemutation) and non-transgenic age-matched littermates (n=a minimum of 12/group) are treated with vehicle,NGP555 (25 mg/kg) once-daily for 30 consecutive days (starting at 5 months of age). A

9、t 6 months, mice areassessed on the Y-maze behavior test 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Kounnas MZ, et al. NGP 555, a -Secretase Modulator, Lowers the Amyloid Biomarker, A42, in Cerebrospinal Fluid while PreventingAlzheimers Disease Cognitive Decline in Rodents. Alzheimers Dement (N Y). 2017 Jan;3(1):65-73.McePdfHeightCaution: Product has not been fully validated for m