Aurora Kinases-IN-3

Aurora Kinases-IN-3 (Compound 15a) is an orally active AURKB inhibitor that elicits an AURKB-suppressive activity by disrupting the mitotic localization of AURKB, rather than inhibiting its phosphorylation of H3 at Ser10[1].

Signaling Pathways >> Epigenetics >> Aurora Kinase

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Aurora Kinase

Signaling Pathways >> Cell Cycle/DNA Damage >> Polo-like Kinase (PLK)

AURKB[1]

Aurora Kinases-IN-3 (Compound 15a) (40 nM; 6 h) disrupts localization of AURKB, MKLP1, and PLK at the spindle midzone to prevent spindle midzone microtubule assembly in RPE-MYCBCL2 cells. Aurora Kinases-IN-3 disrupts the localization of AURKB as early as anaphase, producing downstream consequences that blocked cytokinesis[1]. Aurora Kinases-IN-3 (1-10 μM; 3 days) shows wide spectrum of growth suppression in human cancer cell lines[1]. Cell Viability Assay[1] Cell Line: NCI–H23, A549, HCT116, SW480, MDA-MB-231, HeLa and NCI-87 cells Concentration: 1, 2.5, 5, or 10 μM Incubation Time: 3 days Result: Exhibited the EC50 values of about 10 nM in most cell lines.

Aurora Kinases-IN-3 (Compound 15a) (50 mg/kg; oral; twice a day for 7 days) 抑制小鼠肺部肿瘤的生长[1]。 Animal Model: Female BALB/c nude mice bearing a xenograft of the human lung cancer cell line NCI–H23[1] Dosage: 50 mg/kg Administration: Oral gavage, twice a day for 7 days Result: Elicited a mitotic arrest and induced cell death by apoptosis. Effectively suppressed the growth of the tumor and reduced the cellularity of tumor tissue. Animal Model: Female BAL B/c nude mice[1] Dosage: 50 mg/kg Administration: Oral administration (Pharmacokinetic Analysis) Result: After oral delivery in PEG300, achieved adequate plasma exposure, the mean value of dose-normalized area under the dose-response curve (AUC) was 0.35 x h/(mg/kg), Cmax was 6.9 μM. Was barely absorbed after oral gavage in the hydrophilic hydroxypropyl methylcellulose (HPMC) formulation.

[1]. Lv G, et al. 2-Phenoxy-3, 4'-bipyridine derivatives inhibit AURKB-dependent mitotic processes by disrupting its localization. Eur J Med Chem. 2023 Jan 5;245(Pt 1):114904.