CHZ868 - JAK 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECHZ868Cat. No.: HY-18960CAS No.: 1895895-38-1分式: CHFNO分量: 423.42作靶點(diǎn): JAK作通路: Epigenetics; JAK/STAT Signaling; Stem Cell/Wnt儲(chǔ)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(shí)驗(yàn) DMSO : 150 mg/mL (354.26

2、mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.3617 mL 11.8086 mL 23.6172 mL5 mM 0.4723 mL 2.3617 mL 4.7234 mL10 mM 0.2362 mL 1.1809 mL 2.3617 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 CHZ868是類型II的JAK2抑制劑，抑制EPOR JAK2 WT Ba/F

3、3 cell細(xì)胞的IC50值為0.17 M。IC50 & Target JAK2110 nM (IC50)體外研究CHZ868 potently inhibits constitutive JAK2 and STAT5 phosphorylation in JAK2V617F SET2 cells. CHZ8681/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEpotently inhibits the proliferation of SET2 cells (GI50=59nM), and has 6-fold less growth inhi

4、bitory activityagainst CMK cells (GI50=378nM) 1. At 100 nM CHZ868 has activity against 26 kinases, including JAK2 andTYK2. CHZ868 is thought to engage with the hinge region of JAK2 through two H-bonds, formed betweenthe amino-pyridine of CHZ868 and the backbone-NH/CO of L932, while the pyridine is o

5、ccupying the adeninepocket of the ATP binding site. CHZ868 potently suppresses the growth of CRLF2-rearranged human B-ALLcells, abrogates JAK2 signaling 2.體內(nèi)研究 CHZ868 is characterized by high passive permeability, good metabolic stability, and low water solubility, aswell as by moderate blood cleara

6、nce and good oral bioavailability, making it suitable for in vivo use. CHZ868improves survival in mice with human or murine B-ALL. CHZ868 and dexamethasone synergistically inducesapoptosis in JAK2-dependent B-ALLs and further improves survival compared to CHZ868 alone 2.PROTOCOLCell Assay 2 CHZ868 i

7、s dissolved in DMSO to make 10 mM stock solution and diluted in culture media. Cells are treatedwith CHZ868 (0, 0.05, 0.1, 0.2 M) or vehicle (DMSO). After 48 hr (Ba/F3 cells) or 72 hr (MHH-CALL4 andPDX cells), CellTiter-Glo Luminescent Cell Viability Assay is added (10 L undiluted or 25 L of a 1:2 d

8、ilutionin each well) and plates are read 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: CHZ868 is reconstituted in 0.5% methylcellulose / 0.5% Tween-80 and administered at doses of 10 orAdministration 2 30 mg/kg/day by oral gavage. Pharm

9、acokinetic/pharmacodynamic and efficacy studies in the mouse modelof rhEpo-induced polycythemia are carried out essentially as reported. Detection of STAT5 phosphorylationin spleen lysates by Meso Scale Discovery is performed 2.MCE has not independently confirmed the accuracy of these methods. They

10、are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Leukemia. 2019 Jun;33(6):1373-1386. Biomed Pharmacother. 2018 Mar;99:278-285.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Meyer SC, et al. CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy inMyeloproliferative Neoplasms. Cancer Cell. 2015 Jul 13;28(1):15-28.2. Wu SC, et al. Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia. Cancer Cell. 2015 Jul 13;28(1):29-41.McePdfHeightCaution: Product has not been