αβ-Tubulin-IN-1 is a potent, orally active inhibitor of αβ-Tubulin that blocks the cell cycle at the G2/M phase and induces apoptosis. It inhibits tumor cell migration and metastasis, exhibiting significant antitumor efficacy.

αβ-Tubulin-IN-1 (compound 12b) induces concentration-dependent degradation of αβ-tubulin in HeLa and K562 cells (0-10 μM) within 16 hours, demonstrating potent cytotoxic effects [1]. Administered at 0-300 nM for 48 hours, it triggers G2/M cell cycle arrest and promotes apoptosis in A2780S and A2780T cells [1]. Additionally, αβ-Tubulin-IN-1 significantly inhibits tumor cell migration and metastasis in HUVEC cells at 0, 1.25, 2.5, 5, and 10 nM over 24 and 48 hours, achieving inhibition rates of 76.21% and 85.07%, respectively [1]. It exhibits anti-proliferative activity across various cell lines (HeLa, A2780S, MCF-7, Raji, H460), with IC50 values ranging between 5 and 14 nM after 24 hours [1]. Western blot analysis reveals that treatment with 10 μM for 16 hours in HeLa cells notably promotes tubulin degradation by targeting the colchicine site via the ubiquitin-proteasome pathway. Cell viability assays in select cell lines (A2780S, A2780T, A549, A549T, MCF7, MCF7/ADR) exposed for 24 hours show potent cytotoxicity, with IC50 values ranging from 11.3 to 63.8 nM [1]. Further analysis in A2780S and A2780T cells treated with 0, 3, 10, 30, 100, and 300 nM for 48 hours confirms its capability to induce G2/M cell cycle arrest and significant apoptosis [1].

αβ-Tubulin-IN-1 is administered either intravenously or orally in vivo, with doses of 5 mg/kg demonstrating this versatility. At increasing doses of 10, 20, and 40 mg/kg administered intravenously three times a week for 2-4 weeks, it exhibits dose-dependent antitumor efficacy in rat models, as highlighted by statistical analysis [1]. The pharmacokinetic parameters in rats reveal differences in half-life, clearance, volume of distribution at steady-state, area under the curve, and maximum concentration between intravenous and oral routes for a 5 mg/kg dosage, indicating oral bioavailability of 30.70%. In female Balb/C and athymic nude mice with A2780S and A2780T Xenograft models, the compound shows significant tumor growth inhibition at the same dosing schedule, albeit with varied efficacy in PTX-resistant A2780T xenografts and no acceptable antitumor effect observed at 40 mg/kg orally.