IQTub4P

IQTub4P is a potent microtubule (MT) inhibitor. IQTub4P has the cytotoxicity in in HeLa cells, with EC50 of 170 nM. IQTub4P inhibits microtubule structure and function. IQTub4P is well-tolerated in vivo[1].

Research Areas >> Cancer

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

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

IQTub4P (48 h) shows strong dose-dependent cytotoxicity in HeLa cells[1]. IQTub4P (0-750 nM, 15 min) shows dose-dependent microtubule network depolymerisation, leads to mitotic arrests and the formation of aberrant multipolar spindles with resulting unstructured chromosome alignment at 120 nM[1]. IQTub4P (0-1.25 μM, 24 h) shows potent induction of G2/M arrest[1]. IQTub4P (10 μM, 2 min) shows potent inhibition of cellular tubulin polymerisation dynamics[1]. Cell Viability Assay Cell Line: HeLa cells[1] Concentration: Incubation Time: 48 h Result: Showed strong dose-dependent cytotoxicity in HeLa cells, with EC50 of 170 nM, and displayed near-identical cytotoxicity in cell culture as its free phenol form IQTub4 (EC50 = 120 nM). Cell Cycle Analysis Cell Line: HeLa cells[1] Concentration: 0, 0.06, 0.12, 0.5, 0.75, 1.25 μM Incubation Time: 24 h Result: Showed potent induction of G2/M arrest, and showed extensive G2/M-arrest from 500 nM.

IQTub4P (Balb/c mice, 25 mg/kg, IP and IV, once every two days, 3 administrations) is well-tolerated in vivo and can avoid short-term cumulative toxicity[1]. Animal Model: Balb/c mice (female)[1] Dosage: 25 mg/kg Administration: IP and IV, 3 administration, 48 h intervals Result: Could avoid short-term cumulative toxicity, and was well-tolerated in vivo, with a single-administration maximal tolerated dose of 32 mg/kg (i.p.) and 50 mg/kg (i.v.).

[1]. Kraus Y, Glas C, Melzer B, et al. Isoquinoline-based biaryls as a robust scaffold for microtubule inhibitors. Eur J Med Chem. 2020;186:111865.