2014
DOI: 10.1038/ja.2014.76
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Actinopyrone D, a new downregulator of the molecular chaperone GRP78 from Streptomyces sp.

Abstract: A new downregulator of the molecular chaperone GRP78, actinopyrone D, was isolated together with a known related compound, PM050463, from Streptomyces sp. RAG92. The molecular formula of actinopyrone D was established as C25H36O4 by high-resolution FAB-MS. NMR spectroscopic analysis revealed the structure of actinopyrone D, which consists of an α-methoxy-γ-pyrone ring and a C17 side chain containing a cis olefin moiety. Actinopyrone D and PM050463 dose-dependently inhibited 2-deoxyglucose-induced luciferase ex… Show more

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Cited by 11 publications
(9 citation statements)
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“…B. abortus takes advantage of VceC to interact with the ER chaperone GRP78 and localizes to the ER in HeLa cells (de Jong et al, 2013 ). Streptomyces inhibits GRP78 protein expression and induces cell death under ER stress (Hayakawa et al, 2014 ). Currently, Nexavar/Stivarga/Votrient is used to target GRP78 in the treatment of human malignancies, viral infections and bacterial diseases (Roberts et al, 2015 ).…”
Section: Discussionmentioning
confidence: 99%
“…B. abortus takes advantage of VceC to interact with the ER chaperone GRP78 and localizes to the ER in HeLa cells (de Jong et al, 2013 ). Streptomyces inhibits GRP78 protein expression and induces cell death under ER stress (Hayakawa et al, 2014 ). Currently, Nexavar/Stivarga/Votrient is used to target GRP78 in the treatment of human malignancies, viral infections and bacterial diseases (Roberts et al, 2015 ).…”
Section: Discussionmentioning
confidence: 99%
“…14 The only difference of pyrone ring formation in the biosynthetic pathway is the absence of amidation. 15 Actinopyrones with α -methoxy- γ -pyrone ring, such as actinopyrones A-D, 16,17 M050511,PM050463, PM060054, and PM060431, 18 were also discovered from Streptomyces strains. Not only the chemical structural similarity, actinopyrones showed resembling antibiotic/antitumor activities and related biosynthetic pathway with piericidins.…”
Section: Resultsmentioning
confidence: 99%
“…A further ECD analysis led to the establishment of the absolute configuration of 95. effect against glutamate-induced cytotoxicity in HT22 murine hippocampal neuronal cells. Besides, two 4-pyrone propionates, 99 and 100, constructed a relatively long side chain, were produced by an actinomycete Streptomyces sp [58,59]. 99 dose-dependently inhibited luciferase expression in 2deoxyglucose treated HT1080 human fibrosarcoma cells (IC50 = 7.8 nM) and it could also inhibit GRP78 protein expression and induce cell death under endoplasmic reticulum stress.…”
Section: Mar Drugs 2020 18 X 6 Of 23mentioning
confidence: 99%