ON1231320

Biological Activity

ON1231320 is a highly specific polo like kinase 2 (PLK2) inhibitor with an IC50 of 0.31 μM. ON1231320 blocks tumor cell cycle progression in the G2/M phase in mitosis, causing apoptotic cell death. ON1231320, an arylsulfonyl pyrido-pyrimidinone, has antitumor activity[1][2]. ON1231320 (Compound 7ao) has no inhibitory activity against PLK1, PLK3 and PLK4 (all IC50>10 μM)[1]. ON1231320 (0-5 μM; 24 hours) activates programmed cell death in human tumor cells[1]. ON1231320 inhibits cell proliferation in 16 tumor cell lines (DU145, MCF-7, BT474, SK-OV-3, MIA-PaCa-2, SK-MEL-28, A549, U87, COLO-205, HELA, H1975, RAJI, U205, K562, GRANTA-519; IC50= 0.035-0.2 μM)[1]. ON1231320 does not appreciably inhibit tubulin polymerization[1]. ON1231320 does not affect normal human fibroblasts[2]. ON1231320 (Compound 7ao; 75 mg/kg; IP; alternate days (Q2D) for 20 days) results in significant inhibition of tumor growth[1].

References

[1]. M V Ramana Reddy, et al. Discovery of 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one (7ao) as a potent selective inhibitor of Polo like kinase 2 (PLK2). Bioorg Med Chem. 2016 Feb 15;24(4):521-44. [2]. Shashidhar S. Jatiani, et al. Abstract 643: Targeting cancer with a selective ATP-mimetic inhibitor of polo like kinase-2.