Microtubule inhibitor 2 is a highly potent and selective microtubule inhibitor, which is orally active. It induces cell death via ferroptosis, and exhibits notable antitumor activity [1].

Microtubule inhibitor 2 (compound 33) (48 h) shows antiproliferative activity with IC 50 values of 0.01, 0.02, 0.02, 0.04, 0.05 μM for A549, Hela, A2780, HCT-8, MCF-7 cells, respectively [1]. Microtubule inhibitor 2 shows selective toward normal human cells and cancer cells (IC 50 s of 0.01, 0.04, 1.45, 1.32,0.54 μM for A549, quiescent HUVECs, LO2, HLF, MCF-10A cells, respectively) [1]. Microtubule inhibitor 2 (48 h) shows antiproliferative activity toward drug-resistant cancer cells (IC 50 s of 0.02, 0.07, 0.04 for A549/ADM, HCT-8/VCR, A2780/TAX cells, respectively) [1]. Microtubule inhibitor 2 (5, 10, 20 nM; 24 h) dramatically disrupts the dynamic balance of the tubulin microtubule system, induces the multipolarization of the mitotic spindle, and interfered with the mitosis of A549 cells [1]. Microtubule inhibitor 2 (5, 10, 20 nM, 24 h, 48 h) arrests cell cycle progression at the G2/M phase in a dose and time-dependent manner [1]. Microtubule inhibitor 2 triggers cell death through ferroptosis rather than apoptosis [1]. Cell Proliferation Assay [1] Cell Line: A549, Hela, A2780, HCT-8, MCF-7 cells Concentration: Incubation Time: 48 h Result: Showed antiproliferative activities with IC 50 values of 0.01, 0.02, 0.02, 0.04, 0.05 μM for A549, Hela, A2780, HCT-8, MCF-7 cells, respectively. Cell Cycle Analysis [1] Cell Line: A549 cells Concentration: 5, 10, 20 nM Incubation Time: 24 h, 48 h Result: Arrested cell cycle progression at the G2/M phase in a dose and time-dependent manner.

Microtubule inhibitor 2 (10 mg/kg; p.o.)displays excellent oral bioavailability (F% = 69.45) [1]. Microtubule inhibitor 2 (10 mg/kg; i.p.; every other day for 22 days) shows antitumor activity and the level of tumor growth inhibition was 78.63% [1]. Pharmacokinetic Parameters of Microtubule inhibitor 2 in Male Institute of Cancer Research (ICR) mice (18 23 g) [1]. p.o. i.v. dose (mg/kg) 10 1 T 1/2 (h) 2.12 0.62 T max (h) 0.25 0.08 T max (ng/mL) 776.31 871.40 AUC (0-t) (h ng -1 mL) 2432.04 350.19 AUC (0-∞) (h ng -1 mL) 2463.76 353.02 MRT (h) 2.57 0.68 CL (mL h -1 kg -1 ) - 2855.67 F % 69.45 - Animal Model: Male Institute of Cancer Research (ICR) mice (18 23 g) [1] Dosage: 10 mg/kg Administration: Result: Displayed excellent oral bioavailability (F% = 69.45). Animal Model: Male BALB/c nude mice (5 weeks old, 18 20 g) (A549 xenograft models) [1] Dosage: 10 mg/kg Administration: i.p.; every other day, 22 days Result: Showed antitumor activity and the level of tumor growth inhibition was 78.63%.