title: Natural Product-Derived Spirooxindole Fragments Serve as Privileged Substructures for Discovery of New Anticancer Agents.
abstract: The utility of natural products for identifying anticancer agents has been highly pursued in the last decades and over 100 drug molecules in clinic are natural products or natural product-derived compounds. Natural products are believed to be able to cover unexplored chemical space that is normally not occupied by commercially available molecule libraries. However, the low abundance and synthetic intractability of natural products have limited their applications in drug discovery. Recently, the identification of biologically relevant fragments derived from biologically validated natural products has been recognized as a powerful strategy in searching new biological probes and drugs. The spirocyclic oxindoles, as privileged structural scaffolds, have shown their potential in designing new drugs. Several anticancer drug candidates such as SAR405838, RO8994, CFI-400945 and their bioisosteres are undergoing clinical trials or preclinical studies. To highlight the significant progress, we focus on illustrating the discovery of SAR405838, RO8994, CFI-400945 and their bioisosteres for cancer therapy using substructure-based strategies and discussing modes of action, binding models and preclinical data.
authors.affiliation: School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, P. R. China. zzuyubin@hotmail.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Yi-Chao
authors.initials: YC
authors.lastname: Zheng
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Shi
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Qi
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry*; D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D007191:Indazoles / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: C000592365:2-(3-(4-((2,6-dimethylmorpholino)methyl)styryl)-1H-indazol-6-yl)-5'-methoxyspiro(cyclopropane-1,3'-indolin)-2'-one; D000970:Antineoplastic Agents; D001688:Biological Products; D007191:Indazoles; D007211:Indoles; C000600870:RO8994; D013141:Spiro Compounds; C000593797:SAR405838