Unknown

Dataset Information

0

A landmark in drug discovery based on complex natural product synthesis.


ABSTRACT: Despite their outstanding antitumour activity in mice, the limited supply from the natural sources has prevented drug discovery/development based on intact halichondrins. We achieved a total synthesis of C52-halichondrin-B amine (E7130) on a >10?g scale with >99.8% purity under GMP conditions. Interestingly, E7130 not only is a novel microtubule dynamics inhibitor but can also increase intratumoural CD31-positive endothelial cells and reduce ?-SMA-positive cancer-associated fibroblasts at pharmacologically relevant compound concentrations. According to these unique effects, E7130 significantly augment the effect of antitumour treatments in mouse models and is currently in a clinical trial. Overall, our work demonstrates that a total synthesis can address the issue of limited material supply in drug discovery/development even for the cases of complex natural products.

SUBMITTER: Kawano S 

PROVIDER: S-EPMC6572832 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications


Despite their outstanding antitumour activity in mice, the limited supply from the natural sources has prevented drug discovery/development based on intact halichondrins. We achieved a total synthesis of C52-halichondrin-B amine (E7130) on a >10 g scale with >99.8% purity under GMP conditions. Interestingly, E7130 not only is a novel microtubule dynamics inhibitor but can also increase intratumoural CD31-positive endothelial cells and reduce α-SMA-positive cancer-associated fibroblasts at pharma  ...[more]

Similar Datasets

| S-EPMC7757247 | biostudies-literature
| S-EPMC4791574 | biostudies-literature
| S-EPMC6099656 | biostudies-literature
| S-EPMC4162403 | biostudies-literature
| S-EPMC2533854 | biostudies-other
| S-EPMC3103991 | biostudies-literature
| S-EPMC4958146 | biostudies-literature
| S-EPMC6800021 | biostudies-literature
| S-EPMC3026905 | biostudies-literature
| S-EPMC5488202 | biostudies-literature