HLM006474-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEHLM006474Cat. No.: HY-16667CAS No.: 353519-63-8分式: CHNO分量: 399.48作靶点: Others作通路: Others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 : 25 mg/mL (62.58 mM; Need ultrasonic)H2O : 40% PEG300 5

2、% Tween-80 45% salineSolubility: 2.5 mg/mL (6.26 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.26 mM); Suspended solution; Need ultrasonic3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (6.26 mM)

3、; Clear solutionBIOLOGICAL ACTIVITY物活性 HLM006474种光谱的 E2F 抑制剂，在 A375 细胞中，可抑制 E2F4 DAN 结合，IC50 值为 29.8 M。IC50 & Target IC50: 29.8 M (E2F4 DNA-binding) 1体外研究 HLM006474 shows little activities against E2F4 DNA-binding in A375 cells at 10 and 20 M, apparentlyinhibits E2F4 DNA-binding at 40 M, and increas

4、ingly suppressses the effect at 60 and 80 Mconcentrations. HLM006474 (40 M) inhibits E2F4 activity via suppression of its DNA-binding activity anddown regulation of its expression. HLM006474 (40 M) also significantly induces apoptosis in A375 and 231cell lines for 24 hours. HLM006474 dramaticly redu

5、ces cyclin D3 protein expression, and is a potent inducerof PARP cleavage 1. HLM006474 reduces the viability of both SCLC and NSCLC lines with IC50 rangingfrom 15 to 75 M. HLM006474 (60 M) increases the expression of several known E2F-regulated genes aftershort treatments in H292 and H1299 cell line

6、s. HLM006474 (20 M) weakly synergizes with paclitaxel, butthere is antagonism between HLM006474 and cisplatin and gemcitabine in H1299 cells 2. HLM006474leads to a decrease in the mRNA levels of MAD2. Furthmore, HLM006474 apparently suppresses theincrease of Mad2 protein and pRb-S780 signal but not

7、the level of Skp2 protein in human lung cancer A549cellss 3.PROTOCOLCell Assay 2 The antiproliferative activity of compounds and their combinations is evaluated using a high-throughputCellTiter-Blue cell viability assay. For the assays, 1000 cells in 24 L are plated in 384-well plates andincubated o

8、vernight at 37C, 5% CO2. The next day, the drugs are diluted in media and 6 L of thesedilutions added to appropriate wells using an automated pipetting station. Four replicate wells are used foreach drug concentration. The cells are incubated with the drug for 120 hours, at which time, 5 L CellTiter

9、-Blue reagent is added. Cell viability is assessed by the ability of the remaining treated cells to bioreduceresazurin to resorufin (579 nm Ex/584 nm Em). Fluorescence is read with a Synergy HT microplate reader.IC50s are determined using a sigmoidal equilibrium model regression using XLfit version

10、4.3.2 and is definedas the concentration of drug required for a 50% reduction in growth/viability. For 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell viability assays, CellTiter 96AQueous One Solution is added according to vendor instructions to c

11、ells for 2 hours following treatment withdrug at the noted dose for 72 hours. All experiments are performed in triplicate and repeated at least threetimes 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 J Mol Med (Berl). 2019 Jun 14.2/3 Ma

12、ster of Small Molecules 您边的抑制剂师www.MedChemESee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Ma Y, et al. A small-molecule E2F inhibitor blocks growth in a melanoma culture model. Cancer Res. 2008 Aug 1;68(15):6292-9.2. Kurtyka CA, et al. E2F inhibition synergizes with paclitaxel in lung cancer cell lines. PLoS One. 2014 May 15;9(5):e96357.McePdfHeightCaution