Division of Natural Drug Discovery, Department of Drug Development Promotion
to Laboratory Sites
Outline of the research
The Natural Drug Discovery Laboratory focuses on natural products–based anticancer drug discovery and cancer metabolism research, aiming to identify novel drug seeds against refractory cancers, particularly pancreatic cancer. Within the tumor microenvironment, cancer cells are exposed to severe nutrient and oxygen deprivation but survive by rewiring their energy metabolism, a phenotype known as tolerance to nutrient starvation or “austerity.” By targeting this tolerance through an antiausterity strategy, we explore traditional medicinal resources worldwide to discover potent natural anticancer agents and to elucidate their structures and mechanisms of action, paving the way for next‑generation cancer therapeutics.
Research Projects
- Antiausterity screening: We evaluate extracts and fractions from traditional medicines and medicinal plants (e.g., Kampo formulas, Ayurvedic herbs) for antiausterity activity under nutrient-deprived conditions using human pancreatic cancer cell lines such as PANC-1.
- Isolation and structural elucidation of natural anticancer agents: Using bioassay-guided fractionation together with HPLC, NMR, and mass spectrometry (MS, Orbitrap-MS), we isolate and characterize promising natural anticancer agents (antiausterity agents) and clarify their novel scaffolds and structure–activity relationships (SAR).
- Mechanistic and metabolomic studies: We investigate mechanisms of action focusing on signaling and cell-death pathways related to nutrient starvation tolerance, including the PI3K/AKT/mTOR pathway and autophagy, and apply FT-NMR- and Orbitrap-MS–based metabolomics to profile metabolic reprogramming and identify biomarker candidates in pancreatic cancer cells.
- Translational research and international collaboration: In collaboration with universities, research institutes, and hospitals in Japan and overseas, we optimize natural product lead compounds and conduct preclinical studies, building an internationally oriented platform for natural products–based drug discovery and translation to clinical application.
