K-858

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

有丝分裂驱动蛋白 Eg5 ATP 酶活性的有效选择性抑制剂，IC50 为 1.3 uM。

A potent, selective inhibitor of mitotic kinesin Eg5 ATPase activity with IC50 of 1.3 uM; displays >150-fold more selective for Eg5 than other members of the kinesin superfamily; induces mitotic arrest, apoptosis, and cell growth inhibition through the activation of the Mad2-mediated spindle checkpoint, and has no effect on microtubule polymerization; exhibits potent antitumor activity in xenograft models of cancer, and induces the accumulation of mitotic cells with monopolar spindles in tumor tissues.Breast Cancer Preclinical.

K858 Racemic is an ATP-uncompetitive inhibitor of Eg5 with an IC50 of 1.3 μM. K858 does not inhibit the ATPase activity of the mitotic kinesins CENP-E and MKLP1, or the conventional kinesin heavy chain even at 200 μM. K858 induces mitotic arrest and growth inhibition via the activation of the Mad2-mediated spindle checkpoint. K858 (5 μM) induces mitotic cell death in cancer cells but not in normal cells. K858 (1, 10, 100 μM) inhibits the MCF7, BT474 and SKBR3 cell lines, and only at 10 and 100 μM suppresses MDA-MB231 cell line after treatment for 24 h. K858 incereases Bax/Bcl2 RNA ratio and survivin in the four cell lines. Furthermore, the up-regulation of survivin is totally reversed by wortmannin (phosphoinositide 3-kinase AKT) in MCF7 cells.

K858 (50, 150 mg/kg, p.o.) shows antitumor activity in an A2780 ovarian cancer xenograft model, also inhibits tumor grwoth in a HCT116 colon cancer xenograft model via 100 mg/kg twice a day orally for 5 days. K858 (100 mg/kg, p.o., qd ×5) displays no neurotoxic side effects in mice.

K-858 | K 858

Cytoskeleton/Cell Adhesion Molecules

Kinesin

Eg5ATPase

Cancer

Breast Cancer

72926-24-0

277.3421

C13H15N3O2S

>98% (HPLC)

10 mM in DMSO

CC(NC1=NN(C(C)=O)C(C2=CC=CC=C2)(C)S1)=O

Acetamide, N-(4-acetyl-4,5-dihydro-5-methyl-5-phenyl-1,3,4-thiadiazol-2-yl)-

(-20℃)

With Ice Pack

≥ 2 years