K 858

Cas No.:	72926-24-0
Chemical Name:	N-(4-acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)a Cetamide
Synonyms:	N-(4-Acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)a cetamide;2,4,6-Cycloheptatrien-1-one, 3-acetyl-5,7-dibromo-2-hydroxy-;3-acetyl-5,7-dibromotropolone;ACMC-20mef0;AGN-PC-00O3CS;3-acetyl-5-acetylamino-2-methyl-2-phenyl-2,3-dihydro-[1,3,4]thiadiazole;CTK0G1775;K-858;K858;N-(4-Acetyl-4,5-dihydro-5-methyl-5-phenyl-1,3,4-thiadia zol-2-yl)acetamide;N-(4-Acetyl-4,5-dihydro-5-methyl-5-phenyl-1,3,4-thiadiazol-2-yl)acetamide;K858 (Racemic)
SMILES:	CC(NC1=NN(C(C)=O)C(C2=CC=CC=C2)(C)S1)=O
Formula:	C13H15N3O2S
M.Wt:	277.3421
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	K858 Racemic is an ATP-uncompetitive inhibitor of Eg5 with an IC50 of 1.3 μM.
In Vivo:	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[1].
In Vitro:	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[1]. 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[2].