Lu, T.Goh, A.W.Yu, M.Adams, J.Lam, F.Teo, T.Li, P.Noll, B.Zhong, L.Diab, S.Chahrour, O.Hu, A.Abbas, A.Liu, X.Huang, S.Sumby, C.Milne, R.Midgley, C.Wang, S.2014-02-032014-02-032014Journal of Medicinal Chemistry, 2014; 57(6):2275-22910022-26231520-4804http://hdl.handle.net/2440/81860ON01910.Na is a highly effective anticancer agent that induces mitotic arrest and apoptosis. Clinical studies with ON01910 in cancer patients have shown efficacy along with an impressive safety profile. While ON01910 is highly active against cancer cells, it has a low oral availability and requires continuous intravenous infusion or multiple gram doses to ensure sufficient drug exposure for biological activity in patients. We have identified two novel series of styrylsulfonyl-methylpyridines. Lead compounds 8, 9a, 18 and 19a are highly potent mitotic inhibitors and selectively cytotoxic to cancer cells. Impressively, these compounds possess excellent pharmaceutical properties and two lead drug candidates 9a and 18 demonstrated antitumor activities in animal models.enCell Line, TumorMicrosomes, LiverAnimalsMiceRatsSulfonamidesAminopyridinesStyrenesSulfonesGlycineAnnexin A5Antineoplastic AgentsIndicators and ReagentsCrystallography, X-RayMagnetic Resonance SpectroscopyArea Under CurveXenograft Model Antitumor AssaysCell CycleApoptosisCell ProliferationStructure-Activity RelationshipBiological AvailabilityDrug DesignModels, MolecularHalf-LifeMass SpectrometryDrug DiscoveryKaplan-Meier EstimateJournal article00300001932014020117403910.1021/jm401961497 Expanding Knowledge9701 Expanding Knowledge970103 Expanding Knowledge in the Chemical Sciences03 Chemical Sciences0304 Medicinal and Biomolecular Chemistry030401 Biologically Active Molecules0003335784000082-s2.0-8489742599964199Sumby, C. [0000-0002-9713-9599]