tcsc0233 SB-743921

SB-743921 is a potent inhibitor of the mitotic kinesin KSP (Eg5), with a K_i of 0.1 nM.

IC50 & Target: Ki: 0.1 nM (Eg5)^[1]

In Vitro: SB-743921 is a potent inhibitor of Eg5, with a K_i of 0.1 nM^[1]. SB-743921 (1 nM) potently inhibits colony forming cell (CFC) formation of chronic myeloid leukemia (CML) primary cells, but exhibits slight inhibitory activities on the colony-forming ability of normal bone marrow progenitors. SB-743921 (1, 3 nM) induces apoptosis of CML primary CD34 + cells, and shows slight effect on normal CD34 + cells. SB-743921 (2 nM) in combination with imatinib displays additive anti-proliferative effect in KCL22 and CML CD34 + cells. Furthermore, SB-743921 overcomes imatinib resistance in CML cells. SB-743921 (0.5 nM, 1 nM, 3 nM) inhibits MEK/ERK and AKT signaling in CML cells^[2].

In Vivo: SB-743921 has good oral bioavailability and pharmacokinetics and induces complete tumor regression in nude mice bearing lung cancer patient xenografts^[3].