Tubulin polymerization-IN-41

Tubulin polymerization-IN-41 is a potent tubulin polymerization inhibitor with the IC50 of 2.61 μM. Tubulin polymerization-IN-41 targets the Colchicine-binding site of tubulin. Tubulin polymerization-IN-41 has anticancer effects[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

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

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Tubulin polymerization-IN-41 (compound C3) displays remarkable antiproliferative activities with IC50 values of 6.3 nM, 9.2 nM, 8.3 nM, and 8.7 nM for K562, MCF-7, HT29, and HCT116 cells, respectively. Additionally, Tubulin polymerization-IN-41 shows marked activity against Paclitaxel-resistant MCF-7 cells and A549 cells[1]. Tubulin polymerization-IN-41 (compound C3; 5-20 nM) downregulates the expression of acetyl-α-tubulin (Ac-α-tubulin) and upregulated the expression of detyrosinated-α-tubulin (DeY-α-tubulin) in a concentration-dependent manner[1]. Tubulin polymerization-IN-41 (compound C3; 5-20 nM; 24 hours) could arrest cancer cells in the G2/M phase, and induces MCF-7 cells apoptosis in a concentration-dependent manner[1]. Tubulin polymerization-IN-41 (compound C3; 5-20 nM; 24 hours) reduces Ser216 phosphorylation, resulting in cdc2 Tyr15 dephosphorylation and Thr161 phosphorylation, which ultimately leads to the activation of subsequent cdc2/cyclin B1 complex[1]. Cell Cycle Analysis[1] Cell Line: MCF-7 cells Concentration: 5 nM, 10 nM, 20 nM Incubation Time: 24 h Result: Could arrest cancer cells in the G2/M phase. Apoptosis Analysis[1] Cell Line: MCF-7 cells Concentration: 5 nM, 10 nM, 20 nM Incubation Time: 24 h Result: Induced MCF-7 cells apoptosis. Western Blot Analysis[1] Cell Line: MCF-7 cells Concentration: 5 nM, 10 nM, 20 nM Incubation Time: 24 h Result: Induced cdc25c activation.

Tubulin polymerization-IN-41 (compound C3; 5-20 mg/kg; i.p; every two days; for 21 consecutive days) exhibits the significant potency of tumor growth inhibition in a dose dependence without weight loss in the drug-treated period[1]. Animal Model: Five-week-old female athymic nude mice injected with MCF-7 cells[1] Dosage: 5, 10, and 20 mg/kg Administration: Intraperitoneal injection; every two days; for 21 consecutive days Result: Exhibited the significant potency of tumor growth inhibition in a dose dependence without weight loss in the drug-treated period.

[1]. Jiafu Leng, et al. Discovery of Novel N-Heterocyclic-Fused Deoxypodophyllotoxin Analogues as Tubulin Polymerization Inhibitors Targeting the Colchicine-Binding Site for Cancer Treatment. J Med Chem. 2022 Dec 22;65(24):16774-16800.