Largazole: from discovery to broad-spectrum therapy.

Abstract:

:The cyclic depsipeptide largazole from a cyanobacterium of the genus Symploca is a marine natural product with a novel chemical scaffold and potently inhibits class I histone deacetylases (HDACs). Largazole possesses highly differential growth-inhibitory activity, preferentially targeting transformed over non-transformed cells. The intriguing structure and biological activity of largazole have attracted strong interest from the synthetic chemistry community to establish synthetic routes to largazole and to investigate its potential as a cancer therapeutic. This Highlight surveys recent advances in this area with a focus on the discovery, synthesis, target identification, structure-activity relationships, HDAC8-largazole thiol crystal structure, and biological studies, including in vivo anticancer and osteogenic activities.

journal_name

Nat Prod Rep

journal_title

Natural product reports

authors

Hong J,Luesch H

doi

10.1039/c2np00066k

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

449-56

issue

4

eissn

0265-0568

issn

1460-4752

journal_volume

29

pub_type

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