Abstract: Designing of natural product-like compounds using natural products as template structures is an important strategy for the discovery of new drugs. Gambogic acid (GA), which is a Garcinia natural product with a unique caged xanthone scaffold, inhibits potent antitumor activity both in vitro and in vivo. This review summarized the researches on the identification of the antitumor pharmacophore of GA, and the design, structural optimization and structure-activity relationship (SAR) of natural product-like caged xanthones based on it.