AZD7986-INS-1007-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAZD7986Cat. No.: HY-101056CAS No.: 1802148-05-5Synonyms: INS 1007分式: CHNO分量: 420.46作靶點: Dipeptidyl Peptidase作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100

2、 mg/mL (237.83 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.95 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (5.95 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 AZD7986個肽 肽酶 1 (DPP1) 抑制劑，在，狗和兔中的 pIC50 值分

3、別為 6.85, 7.6, 7.7,7.8 和 7.8。IC50 & Target pIC50: 6.85 (human DPP1), 7.6 (mouse DPP1), 7.7 (rat DPP1), 7.8 (dog DPP1), 7.8 (rabbit DPP1) 1體外研究 Results from cell assay show that AZD7986 is a Dipeptidyl peptidase 1 (DPP1) inhibitor with pIC50s of 6.85,7.6, 7.7, 7.8, and 7.8 in human, mouse, rat, dog an

4、d rabbit, respectively. AZD7986 is stable in thepropionaldehyde reactivity assay, with a half-life over 50 h. After differentiation in the presence of AZD7986(38 pM to 10 M), concentration-dependent decreases in cell lysate enzyme activity are observed for DPP1,as well as for all of the three NSPs,

5、NE, Pr3, and CatG. AZD7986 inhibits activation of all three NSPs in aconcentration dependent manner, with pIC50 values of around 7 for all three NSPs. The reduction of theactivities is almost complete, with NE, Pr3, and CatG activities reduced to 4 to 10% of control at 10 MAZD7986 1.體內(nèi)研究 AZD7986 sho

6、ws good stability in plasma, with a half life of 10 h. AZD7986 inhibits activation of NE and Pr3,but not CatG, in bone marrow cell lysates in a dose dependent manner in vivo 1.PROTOCOLKinase Assay 1 Activation of neutrophil serine proteases (NSPs) is assessed in vitro using primary bone marrow deriv

7、edCD34+ neutrophil progenitor cells. Cells are cultured in media supplemented with rhSCF and rhIL-3 for 7days, and then for a further 7 days in the presence of G-CSF and different concentrations of AZD7986 (38pM to 10 M). After harvesting and lysis with 10% Triton X-100 buffer, cell lysates are kept

8、 at -20C until NSPactivity analysis 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cellular potency is studied using the DPP1-expressing monocytic U937 cell line. Briefly, cells grown in RPMIare plated on 384-well polypropylene v-bottom

9、plates at a density of 5105 cells/mL per well. Added to this is10 L of AZD7986 at 37C for 60 min, followed by 350 M Gly-Phe-AFC. The well fluorescence is read usinga multilabel plate reader. Data are analyzed to calculate pIC50 values 1.MCE has not independently confirmed the accuracy of these metho

10、ds. They are for reference only.Animal Rats are used for the in vivo study. Naive rats are dosed orally twice daily with AZD7986 at 0.2, 2, and 20Administration 1 mg/kg/day for 8 days. Attermination, bone marrow is taken by femural aspiration for neutrophil serineproteases (NSPs) activity analysis u

11、sing commercial synthetic peptide substrates 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn)2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE Biochem Pharmacol. 2019 Jun;164:349-367.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Doyle K, et al. Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile BasedClinical Candidate (AZD7986). J Med Chem. 2016 Oct 27;59(20):9457-9472.McePdfHeightCaution: Produ