GSK503 - Histone Methyltransferase 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK503Cat. No.: HY-12856CAS No.: 1346572-63-1分式: CHNO分量: 526.67作靶點(diǎn): Histone Methyltransferase作通路: Epigenetics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 : 44 mg/mL (83.54 mM)* means solub

2、le, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.8987 mL 9.4936 mL 18.9872 mL5 mM 0.3797 mL 1.8987 mL 3.7974 mL10 mM 0.1899 mL 0.9494 mL 1.8987 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 GSK503效特異性的EZH2甲基轉(zhuǎn)移酶抑制劑，Kiapp值為3到27 nM。IC50 & Target Ki:

3、 3 to 27 nM (EZH2) 1體外研究GSK503 inhibits the methyltransferase activity of wild type and mutant EZH2 with similar potency (Kiapp=3-27 nM) and is structurally related to GSK126 and GSK343. GSK503 is 200 fold selective over EZH11/2 Master of Small Molecules 您邊的抑制劑師www.MedChemE(Kiapp=636 nM) and 4000 fo

4、ld selective over other histone methyltransferases 1.體內(nèi)研究 In a melanoma mouse model, conditional EZH2 ablation as much as treatment with the GSK503 stabilizesthe disease through inhibition of growth and virtually abolishes metastases formation without affecting normalmelanocyte biology 2. GSK503 dis

5、plays favorable pharmacokinetics in mice. GSK503, but not vehicle,prevents the formation of germinal center after SRBC or NP-KLH immunization, phenocopying the Ezh2 nullphenotype. GSK503 treatment leads to reduced numbers of GC B-cells by flow cytometry, reduces numberand volume of GCs by immunohist

6、ochemistry, and impairs formation high affinity antibodies 1.PROTOCOLAnimal Mice: To pharmacologically inhibit Ezh2 activity, Tyr:N-RasQ61K Ink4a-/- and C57Bl/6 mice are subjected toAdministration 2 treatment with GSK503, which is diluted (15 mg/mL) in 20% Captisol solution. Efficient Ezh2 inhibitio

7、n isachieved by daily intraperitoneal injections of 150 mg/kg GSK503 over 35 consecutive days. Mice aremonitored during and after treatment to measure GSK503-induced reversible weight loss. C57Bl/6 andFoxn1nu/nu mice engrafted with melanoma cells are subjected to TM and GSK503 treatment as described

8、above 2.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) Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):2961-2966. Patent. US20180263995A1. Oncotarget. 2017 Apr 25;8(35):58654-58667.See more customer validations on HYPERLINK / www.MedChemEREFER

9、ENCES1. Bguelin W, et al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation.Cancer Cell. 2013 May 13;23(5):677-92.2. Zingg D, et al. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumoursuppressors. Nat Commun. 2015 Jan 22;6:6051.McePdfHeightCaution: Product has not been fully validated for med