Tubulin polymerization-IN-28

Tubulin polymerization-IN-28 (compound-4) is a microtubule protein polymerization inhibitor with highly selective anticancer activity. Tubulin polymerization-IN-28 can be activated by NQO1 and effectively release combretastatin A-4 to kill tumor cells. Tubulin polymerization-IN-28 can induce cell apoptosis and be used in anti-cancer research[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

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

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Tubulin polymerization-IN-28 (compound-4) (9-381 nM，48 hours)has a significant inhibitory effect on tumor cells[1]. Tubulin polymerization-IN-28 (compound-4) (10 nM，48 hours) inhibits microtubule assembly with anti-tumor activity[1]. Tubulin polymerization-IN-28 (compound-4) (10 nM，48 hours) causes G2/M phase arrest in cells[1]. Tubulin polymerization-IN-28 (compound-4) (10 nM，24 hours) leads to significant cell apoptosis[1]. Cell Proliferation Assaysup>[1] Cell Line: NQO1-Overexpressing A549, HepG2; Hypoxia-exposed A549 (A549/Hyp), HepG2 (HepG2/Hyp) cells; Taxol-resistant A549 cells (A549/T) Concentration: 9-381 nM Incubation Time: 48 hours Result: Inhibited A549, HepG2, A549/Hyp, HepG2/Hyp, A549/T with IC50values of 10 nM, 26 nM, 72 nM, 85 nM, 56 nM, 74 nM and 88 nM respectively. Immunofluorescencesup>[1] Cell Line: HepG2 Concentration: 10 nM Incubation Time: 48 hours Result: Showed that Tubulin polymerization-IN-28 converted to CA-4, thereby inhibiting microtubule assembly, in the presence of NQO1. Cell Cycle Analysis[1] Cell Line: HepG2 Concentration: 0 nM，10 nM Incubation Time: 48 hours Result: Resulted in an increase in the percentage of G2/M phase cells from 12.71% to 33.49%. Apoptosis Analysis[1] Cell Line: HepG2 Concentration: 0 nM，10 nM Incubation Time: 24 hours Result: Showed the apoptosis rate of cells increasing from 6.54% to 23.93%.

Tubulin polymerization-IN-28 (compound-4) (intraperitoneal injection, every day, 17days) exhibits good anti-cancer activity in HepG2 xenograft-bearing BALB/c mice model in vivo[1]. Animal Model: HepG2 xenograft-bearing BALB/c mice[1] Dosage: 20 mg/kg, 40 mg/kg Administration: Intraperitoneal injection; every day; 17days Result: Resulted in 47.49% reduction in tumor growth at a concentration of 20 mg/kg. Resulted in 54.87% reduction in tumor growth at a concentration of 40 mg/kg.

[1]. Chong Zhang,et al. NQO1-selective activated prodrugs of combretastatin A-4: Synthesis and biological evaluation. Bioorg Chem. 2020 Oct;103:104200.