产品描述

ELR-510444 is a novel microtubule disruptor with potential antivascular effects and in vivo antitumor efficacy, causing a loss of cellular microtubules and the formation of aberrant mitotic spindles and leading to mitotic arrest and apoptosis of cancer cells.

靶点（IC50 & Targe）

Microtubule disruptor,

体外研究

ELR510444 has potent microtubule-disrupting activity, causing a loss of cellular microtubules and the formation of aberrant mitotic spindles and leading to mitotic arrest and apoptosis of cancer cells. ELR510444 potently inhibits cell proliferation with an IC(50) value of 30.9 nM in MDA-MB-231 cells, inhibits the rate and extent of purified tubulin assembly, and displaces colchicine from tubulin, indicating that the drug directly interacts with tubulin at the colchicine-binding site. ELR510444 is not a substrate for the P-glycoprotein drug transporter and retains activity in βIII-tubulin-overexpressing cell lines, suggesting that it circumvents both clinically relevant mechanisms of drug resistance to this class of agents[1].

体内研究

ELR510444 shows potent antitumor activity in the MDA-MB-231 xenograft model. A low concentration of ELR510444 (30 nM) rapidly alters endothelial cell shape[1].

激酶实验

细胞实验

Cell lines: 2H-11 tumor endothelial cells

Concentrations: 1-100 nM

Incubation Time: 1 h

Method: 2H-11 cells are plated on glass coverslips and allowed to attach and grow for 24 h. Drugs are then added for 1 h, and cells are fixed with paraformaldehyde and permeabilized with Triton X-100. F-Actin and DNA are stained with tetramethylrhodamine B isothiocyanate-conjugated phalloidin and DAPI, respectively.

(Only for Reference)

动物实验

Animal Models: BALB/c nude mice

Formulation: 10% DMSO with 10% Cremophor in water.

Dosages: 3, 6, and 12.5 mg/kg

Administration: s.c.

(Only for Reference)

参考文献

[1] Risinger AL, et al. J Pharmacol Exp Ther. 2011, 336(3):652-60.