EZM-2302 - Histone Methyltransferase 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEEZM 2302Cat. No.: HY-111109CAS No.: 1628830-21-6分式: CHClNO分量: 585.09作靶点: Histone Methyltransferase作通路: Epigenetics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 : 125 mg/mL (213.64 mM)* mean

2、s soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.7091 mL 8.5457 mL 17.0914 mL5 mM 0.3418 mL 1.7091 mL 3.4183 mL10 mM 0.1709 mL 0.8546 mL 1.7091 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。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您

3、现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (3.56 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (3.56 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Maste

4、r of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.08 mg/mL (3.56 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 EZM 2302共激活因相关的精氨酸甲基转移酶1 (CARM1) 制剂， IC50值为6 nM。IC50 & Target IC50: 6nM (CARM1) 1体外研究 EZM 2302 binds to CARM1 and is a selective inhibitor of CARM1 activity (IC50=6nM) with broad selectivit

5、yagainst other histone methyltransferases. Treatment of MM cell lines with EZM 2302 leads to inhibition ofPABP1 and SMB methylation and cell stasis with IC50 values in the nanomolar range (9, 31 nM,respectively). EZM 2302 inhibits the in vitro proliferation of multiple hematopoietic cell lines, with

6、 day 14 IC50values of less than 100nM in 9 of 15 cell lines 1.体内研究 EZM 2302 is stable in human hepatocytes (CL 1.PROTOCOLCell Assay 1 Cultured cells in linear/log phase growth are split to a seeding density of 2e5 cells/mL in 220mLs of media,depending on the yield required at the end of the growth p

7、eriod. EZM 2302 is diluted in DMSO and added toeach culture vessel with a final DMSO concentration of 0.2%. Cells are allowed to grow for 96hours. At theconclusion of each treatment period, cells are harvested by centrifugation (5minutes, 1200rpm), and cellpellets are rinsed once with PBS before bei

8、ng frozen on dry ice pending further processing 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats 1Administration 1 Male Sprague-Dawley rats (n=3) are treated with a single dose of EZM2302 at 2mg/kg by intravenous (i.v.)injection and 10mg/kg

9、 by oral gavage administration (p.o.; mouse only), formulated in 5% dextrose in water,pH 3.5. An additional group of rats, cannulated in both the jugular and portal veins are dosed by oral gavage(10mg/kg, in 0.5% methylcellulose in water). Approximately 110L of blood is taken from the animals byretr

10、o-orbital bleeding (mouse), tail vein (rat i.v.) or both jugular and portal vein sampling (rat p.o.) at pre-specified time intervals. The 2h samples are split for parallel determination of blood and plasmaconcentration 1.Mice 1RPMI-8226 cells are inoculated at 5106 cells/mouse and treatment began wh

11、en the mean tumor sizesreach 120mm3 (28 days post-inoculation). CB-17 SCID Mice are assigned into groups using a randomizedblock design. EZM2302 or vehicle (0.5% methylcellulose in water) is administered orally BID at a dosevolume of 37.5, 75, 150, or 300mg/kg for 21 days. Body weights are measured

12、twice a week for the durationof the study. Tumor size is measured twice weekly in two dimensions using a caliper, and the volume isexpressed in cubic millimeters. Animals are euthanized 3hours post-final dose, with blood and tissuescollected for analysis 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEREFERENCES1. Drew AE, et al. Identification of a CARM1 Inhibitor with Potent In Vitro and In Vivo Activity in Preclinical Models of Multiple Myeloma. SciRep. 2017 Dec 21;7(1):17993.McePdfHe