ZL0420 - Epigenetic Reader Domain 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEZL0420Cat. No.: HY-112149CAS No.: 2230496-80-5分式: CHNO分量: 296.32作靶点: Epigenetic Reader Domain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 (421.84 mM; Need ultra

2、sonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 3.3747 mL 16.8736 mL 33.7473 mL5 mM 0.6749 mL 3.3747 mL 6.7495 mL10 mM 0.3375 mL 1.6874 mL 3.3747 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，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保

3、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 (7.02 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 (7.02 mM); Clear solutionBIOLOGICAL ACTIVITY1/2 Master of Small Molecules 您边的抑制剂师www.MedChemE物活

4、性 ZL0420是有效且选择性的 BET 溴结构域 4 (BRD4) 抑制剂，对 BRD4 BD1和 BRD4 BD2 的 IC50 分别为 27 nM和 32 nM。IC50 & Target IC50: 27 nM (BRD4 BD1), 32 nM (BRD4 BD2) 1体外研究 ZL0420 is well docked into the acetyl-lysine (KAc) binding pocket of BRD4, forming key interactions includingthe critical hydrogen bonds with Asn140 direct

5、ly and Tyr97 indirectly via a H2O molecule. ZL0420 exhibitssubmicromolar potency of inhibiting the TLR3-dependent innate immune gene program, including ISG54,ISG56, IL-8, and Gro genes in cultured human small airway epithelial cells (hSAECs) with IC50s of 0.49-0.86 M 1.体内研究 ZL0420 demonstrates poten

6、t efficacy reducing airway inflammation in a mouse model with low toxicity.ZL0420 displays high efficacy and almost completely blocks the profound accumulation of neutrophils aroundthe small and medium sized airways induced by poly(I:C) administration 1.PROTOCOLCell Assay 1 hSAECs are first pretreat

7、ed with a series final concentrations of BRD4 inhibitors from 0.01 nM to 100 M for24 hours and are then added poly(I:C) at 10 g/mL for another 4 hours prior to harvesting the cells. Theharvested cells are first ished with PBS twice and then the total RNA is extracted using acid guanidiniumphenol ext

8、raction. The total RNA is further reverse-transcribed for gene expression analysis by Q-RT-PCR1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 C57BL/6 mice are pre-treated in the absence or presence of the ZL0420 10 mg/kg

9、body weight, via theintraperitoneal route one day prior to poly(I:C) stimulation. The next day, animals are given another dose ofZL0420 immediately followed by intranasal (i.n.) administration of phosphate-buffered saline (PBS, 50 L) orpoly(I:C) (300 g dissolved in 50 L PBS). One day later, the mice

10、 are euthanized. The bronchoalveolarlavage fluid (BALF) and lung tissues of treated mice are collected for further analysis 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Liu Z, et al. Discovery of potent and selective BRD4 inhibitors capable of blocking TLR3-induced acute airway inflammation. Eur J MedChem. 2018 May 10;151:450-461.McePdfHeightCaution: Product has not been fully