SB-743921 (free base)

SB-743921 free base is a potent selective inhibitor of the mitotic kinesin KSP (Eg5), with a K_i of 0.1 nM. SB-743921 free base can induce mitotic arrest, block cell cycle progression, induce apoptosis, and can be used in the research of myeloma, leukemia and other diseases^[1][2]. 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^[2].
SB-743921 (1-3 nM) induces apoptosis of CML primary CD34⁺ cells, and shows slight effect on normal CD34⁺ cells. SB-743921 in combination with imatinib displays additive anti-proliferative effect in KCL22 and CML CD34⁺ cells. Furthermore, SB-743921 overcomes imatinib resistance in CML cells^[2].
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].