|Tubulin polymerization inhibitor|
Sample solution is provided at 25 µL, 10mM.
|Solubility||Soluble in DMSO > 10 mM||Storage||Store at -20°C|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|
|Shipping Condition||Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
D-64131 is an orally small-molecular inhibitor of tubulin with IC50 value of 62 nM .
D-64131 is a synthesized compound that possesses potent anti-mitotic and anti-proliferation effects. It is designed based the 2-aroylindole. D-64131 can inhibit polymerization of tubulin and compete with [3H] colchicine for binding to αβ-tubulin, interfering with the function of mitotic spindle and subsequently causing cell cycle arrest in G2-M phase. D-64131 showed potent anti-proliferation effects in various cancer cell lines such as HeLa/KB cervical carcinoma and U373 glioblastoma cell lines. It also exerted significant inhibition of tumor growth in tumor xenografts. Unlike the natural microtubule inhibitors, D-64131 did not affect the polymerization-dependent GTPase activity of β-tubulin. Besides that, D-64131displayed no cross-resistance toward cell lines .
D-64131 inhibited the polymerization ofbovine brain tubulin with IC50 value of 0.53 μM. It dose-dependently inhibited the binding of [3H]colchicine to biotinylated αβ-tubulin with IC50 value of 0.51 μM.D-64131 showed broad cytotoxicity in various cancer cell lines such as L1210 (IC50 value of 0.102 μM), MCF-7 (IC50 value of 0.04 μM), HT1080 (IC50 value of 0.027 μM) and HT-29 (IC50 value of 0.055 μM). The cytotoxicity was proved to be p53 status-independent since both p53-wild type cell lines and p53 mutant cell lines were equally inhibited. Besides that, the cytotoxicity was cell cycle specific .
In the in vivo assays, oral administration of D-64131 showed significant anti-tumor effects in 19 human tumor cell xenografts with a mean IC50 value of 0.88 μM. Among these xenografts, ovarian, melanomas and colon cancer cells were found to be most sensitive toward D-64131 treatment .
 Beckers T, Reissmann T, Schmidt M, et al. 2-Aroylindoles, a novel class of potent, orally active small molecule tubulin inhibitors. Cancer research, 2002, 62(11): 3113-3119.