Tubulin inhibitor 11

Tubulin inhibitor 11 is a potent and orally active tubulin inhibitor. Tubulin inhibitor 11 targets the Colchicine binding site on tubulin, inhibits tubulin polymerization, promotes mitotic blockade and apoptosis[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Tubulin inhibitor 11 (Compound 48; 0.03-0.1 μM; 12 hours) causes cell cycle arrest at G2/M phase. Tubulin inhibitor 11 reduces cdc2 phosphorylation and increases cyclin B1 and phosphorylation of histone H3 at Ser10 in cells[1]. Tubulin inhibitor 11 (Compound 48; 0.03-0.3 μM; 48 hours) causes cancer cell apoptosis[1]. Tubulin inhibitor 11 (Compound 48) demonstrates favorable antiproliferative activities in DU145 cells with an IC50 of 8 nM[1]. Tubulin inhibitor 11 (Compound 48; 0.03-0.3 μM) significantly reduces the expression levels of acetyl-α-tubulin and α-tubulin in a dose-dependent manner[1]. Cell Cycle Analysis[1] Cell Line: DU145 cells Concentration: 0.01 μM, 0.03 μM, and 0.1 μM Incubation Time: 12 hours Result: Caused cell cycle arrest at G2/M phase. Apoptosis Analysis[1] Cell Line: DU145 cells Concentration: 0.03 μM, 0.1 μM, and 0.3 μM Incubation Time: 48 hours Result: Induced cancer cell apoptosis. Western Blot Analysis[1] Cell Line: DU145 cells Concentration: 0.01 μM, 0.03 μM, and 0.1 μM Incubation Time: 12 hours Result: Reduced cdc2 phosphorylation and increased cyclin B1 and phosphorylation of histone H3 at Ser10 in cells.

Tubulin inhibitor 11 (Compound 48; 5-10 mg/kg; p.o; once daily) shows robust in vivo antitumor efficacies[1]. Animal Model: Male athymic BALB/c nude mice (18-20 g) injected with DU145, NCI-H1299 or A549R cells[1] Dosage: 5 mg/kg, 10 mg/kg Administration: p.o; once daily Result: Effectively suppressed tumor growth.

[1]. Songwen Lin, et al. Optimization of Benzamide Derivatives as Potent and Orally Active Tubulin Inhibitors Targeting the Colchicine Binding Site. J Med Chem. 2022 Dec 22;65(24):16372-16391.