LP-261

LP-261 is a potent and orally active anti-mitotic agent and shows an inhibition of in vitro tubulin polymerization with an EC₅₀ of 3.2 μM^[1]. LP-261 inhibits growth of a human non-small-cell lung tumor (NCI-H522) in vivo and can be used for cancer research^[1]. IC50 & Target: EC50: 3.2 μM (tubulin polymerization)^[1] In Vitro: LP-261 shows potent G2/M block activity in multiple cell lines and exhibits a range of activity from 0.01μM to 0.38 μM across the tested cell lines, the IC₅₀ values for MCF-7, H522, Jurkat, SW-620, BXPC-3, and PC-3 values are 0.01 μM, 0.01 μM, 0.02 μM, 0.05 μM, 0.05μM and 0.07 μM, respectively^[1].
LP-261 exhibits low micromolar potency in the tubulin polymerization assay, the EC₅₀ value of LP-261 is 5.0 μM^[1]. LP-261 has the ability to compete with colchicine for binding to tubulin in a [³H]colchicine competition binding assay, the EC₅₀ (3.2 μM) for LP-261 to inhibit the binding with a potency similar to that of colchicine itself, and it exhibits a 79% inhibition at a conctration of 30 μM^[1].
In Vivo: LP-261 (oral gavage; 4 mg/kg; single dose) displays rapid adsorption by the oral route (T_max=2.0 h), the terminal half-life of 1.4 h ( 0.2 h indicated a moderate rate of elimination in rat, and the volume of distribution (V_ss) is 1.25 L/kg^[1].
LP-261 (oral gavage; 15 or 50 mg/kg; twice daily; 28 days) at 50mg/kg results in an approximately tumor volume of 130 mm³ versus 3769 mm³ in the vehicle treated group, this represents a 96% reduction in mean tumor volume. Meanwhile, LP-261 at 15 mg/kg leads to a 41% inhibition after 28 days in this mouse model^[1].