Design, Synthesis, and Evaluation of Trihalomethyl Ketone Derivatives of Neocarzilin A as Improved Antimetastatic Agents.

ABSTRACT: Vesicle Amine Transport-1 (VAT1) is a protein that is overexpressed in many cancers, including breast cancer, glioblastoma, and angiosarcoma. High VAT1 expression correlates with poor overall survival, and genetic knockout models of VAT1 indicate potent antimigratory activity, suggesting that VAT1 is a promising antimetastasis target. Recently, the natural product neocarzilin A (NCA) from Streptomyces carzinostaticus was reported to be the first validated small-molecule inhibitor of VAT1, having strong activity in metastasis models of angiosarcoma and breast cancer. While knockdown of VAT1 has no effect on cell viability, NCA has significant cytotoxicity, suggesting that NCA is not selective for VAT1. Additionally, NCA has poor aqueous solubility, making in vivo administratio

SUBMITTER: Moriarty NM 

PROVIDER: S-EPMC11659896 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature