LP-261

• CAT Number: I007713
• CAS Number: 915412-67-8
• Molecular Formula: C22H19N3O4S
• Molecular Weight: 421.47
• Purity: ≥95%
• Synonyms: N-[3-(1H-indol-4-yl)-5-(2-methoxypyridine-4-carbonyl)phenyl]methanesulfonamide
• InChI: InChI=1S/C22H19N3O4S/c1-29-21-13-14(6-8-24-21)22(26)16-10-15(11-17(12-16)25-30(2,27)28)18-4-3-5-20-19(18)7-9-23-20/h3-13,23,25H,1-2H3
• InChIKey: YUVDELGTFILMBB-UHFFFAOYSA-N
• SMILES: COC1=NC=CC(=C1)C(=O)C2=CC(=CC(=C2)C3=C4C=CNC4=CC=C3)NS(=O)(=O)C

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].
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].
LP-261 (oral gavage; 4 mg/kg; single dose) displays rapid adsorption by the oral route (Tmax=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 (Vss) 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].

Reference

[1]. Rupa S Shetty, et al. Synthesis and pharmacological evaluation of N-(3-(1H-indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a potent antimitotic agent. J Med Chem. 2011 Jan 13;54(1):179-200
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