title: Discovery and development of natural product oridonin-inspired anticancer agents.
abstract: Natural products have historically been, and continue to be, an invaluable source for the discovery of various therapeutic agents. Oridonin, a natural diterpenoid widely applied in traditional Chinese medicines, exhibits a broad range of biological effects including anticancer and anti-inflammatory activities. To further improve its potency, aqueous solubility and bioavailability, the oridonin template serves as an exciting platform for drug discovery to yield better candidates with unique targets and enhanced drug properties. A number of oridonin derivatives (e.g. HAO472) have been designed and synthesized, and have contributed to substantial progress in the identification of new agents and relevant molecular mechanistic studies toward the treatment of human cancers and other diseases. This review summarizes the recent advances in medicinal chemistry on the explorations of novel oridonin analogues as potential anticancer therapeutics, and provides a detailed discussion of future directions for the development and progression of this class of molecules into the clinic.
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, United States.
authors.forename: Ye
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, United States.
authors.forename: Chunyong
authors.initials: C
authors.lastname: Ding
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, United States.
authors.forename: Na
authors.initials: N
authors.lastname: Ye
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, United States.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, United States.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Wold
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, United States.
authors.forename: Haiying
authors.initials: H
authors.lastname: Chen
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Wild
authors.affiliation: Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, United States.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, United States. Electronic address: jizhou@utmb.edu.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D045786:Diterpenes, Kaurane; D055808:Drug Discovery / Q000379:methods*; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D045786:Diterpenes, Kaurane; C011959:oridonin
keywords: Anticancer agents; Chemical biology; Diterpenoids; Drug discovery; Natural product; Oridonin