CX-5461-dihydrochloride - RNA Polymerase I 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECX-5461 dihydrochlorideCat. No.: HY-13323A分式: CHClNOS分量: 586.54作靶點(diǎn): DNA/RNA Synthesis作通路: Cell Cycle/DNA Damage儲存式: 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) H2O : 25 mg/mL (42.62 mM)* means solu

2、ble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.7049 mL 8.5246 mL 17.0491 mL5 mM 0.3410 mL 1.7049 mL 3.4098 mL10 mM 0.1705 mL 0.8525 mL 1.7049 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 CX-5461 dihydrochloride種有效的，可服的 Pol I 介導(dǎo)的 rRNA synthesi

3、s 抑制劑，在 HCT-116，A375和 MIA PaCa-2 細(xì)胞中，IC50 值分別為 142 nM，113 nM 和 54 nM，對 Pol II 作不 (IC50 25 M)。IC50 & Target IC50: 54 nM (rRNA synthesis, MIA PaCa-2 cells), 113 nM (rRNA synthesis, A375 cells), 142 nM (rRNAsynthesis, HCT-116 cells) 1體外研究CX-5461 is a potent and orally bioavailable inhibitor of Pol I-me

4、diated rRNA synthesis, with IC50s of 142 nM1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEin HCT-116, 113 nM in A375, and 54 nM in MIA PaCa-2 cells, and shows little or no effect on Pol II (IC50,25 M). CX-5461 has modest inhibition on DNA replication and protein translation. CX-5461 also exhibitsb

5、road antiproliferative activity against a panel of human cancer cell lines, with a mean EC50 of 147 nM, buthas minimal effect on viability of nontransformed human cells, with EC50 values of appr 5000 nM. EC50s ofCX-5461 for HCT-116, A375, and MIA PaCa-2 cell lines are 167, 58, and 74 nM, respectivel

6、y. CX-5461induces autophagy and senescence in solid tumor cancer cells, rather than apoptosis, through a p53-independent process 1. E-Myc lymphoma cells from tumor-bearing mice are exquisitely sensitive to CX-5461 with an IC50 of 27.3 nM 8.1 nM for Pol I transcription after 1 hr and IC50 of 5.4 nM 2

7、.1 nM for celldeath after 16 hr. CX-5461 activates p53 via the nucleolar stress response in E-MycLymphoma Cells 2.體內(nèi)研究 CX-5461 displays antitumor activity against human solid tumors in murine xenograft models. CX-5461 (50mg/kg, p.o.) shows significant MIA PaCa-2 growth inhibition with TGI equal to 6

8、9% on day 31 and 79% TGIon A375 on day 32 1. CX-5461 (50 mg/kg, p.o.) inhibits the E-Myc tumor cells with 84% repression in Pol Itranscription at 1 hr posttreatment in C57BL/6 mice. CX-5461 also induces a rapid reduction in tumor burdenin the lymph nodes and a concomitant reduction of spleen size to

9、 within the normal range 2.PROTOCOLCell Assay 1 Cells are plated on 96-well plates and treated the next day with dose response of CX-5461 for 96 hours. Cellviability is determined using Alamar Blue and CyQUANT assays 1.MCE has not independently confirmed the accuracy of these methods. They are for r

10、eference only.Animal Mice 1Administration 1 Animal experiments are performed with 5- to 6-week-old female athymic (NCr nu/nu fisol) mice of Balb/c.Mice are inoculated with athymic (NCr nu/nu fisol) mice in 100 L of cell suspension subcutaneously in theright flank. Tumor measurements are performed by

11、 caliper analysis, and tumor volume is calculated usingthe formula (lw2)/2, where w=width and l=length in mm of the tumor. established tumors (appr 110-120mm3) are randomized into vehicle (50 mM NaH2PO4, pH 4.5), NSC 613327, or CX-5461 treatment groups.Tumor growth inhibition (TGI) is determined on

12、the last day of study according to the formula: TGI (%)=100 (VfD ViD)/ (VfV ViV) 100, where ViV is the initial mean tumor volume in vehicle-treated group, VfV isthe final mean tumor volume in vehicle-treated group, ViD is the initial mean tumor volume in drug-treatedgroup, and VfD is the final mean

13、tumor volume in drug-treated group.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) Nat Commun. 2017 Sep 25;8(1):693. Clin Cancer Res. 2017 Nov 1;23(21):6529-6540. Acta Biomater. 2018 Oct 1;79:317-330. Mol Cancer Ther. 2018 Jun;17(6):1177-118

14、6. Biochim Biophys Acta. 2017 Dec 8;1862(3):615-629.See more customer validations on HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEREFERENCES1. Drygin D et al. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumorgrowth. Cancer Res. 2011 Feb 15;71(4):1418-30.2. Bywater MJ, et al. Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific A