Prunustatin A, a Novel GRP78 Molecular Chaperone Down-regulator Isolated from Streptomyces violaceoniger

  title={Prunustatin A, a Novel GRP78 Molecular Chaperone Down-regulator Isolated from Streptomyces violaceoniger},
  author={Yukiko Umeda and Shuhei Chijiwa and Kazuo Furihata and Keiko Furihata and Sho-hei Sakuda and Hiromichi Nagasawa and Hidenori Watanabe and Kazuo Shin‐ya},
  journal={The Journal of Antibiotics},
In the course of our screening program for regulators of a molecular chaperone GRP78 expression, we isolated a novel inhibitor of GRP78 expression, designated as prunustatin A, from Streptomyces violaceoniger 4521-SVS3. The structure of prunustatin A was determined by a series of NMR analyses to be an oxidized type of the neoantimycin family. Prunustatin A inhibited the expression of GRP78 induced by 2-deoxyglucose in human fibrosarcoma HT1080 cells accompanied by global cell death without… 
Novel GRP78 Molecular Chaperone Expression Down-regulators JBIR-04 and -05 Isolated from Streptomyces violaceoniger
JBIR-04 and -05 inhibited the expression of GRP78 induced by 2-deoxyglucose in human fibrosarcoma HT1080 cells, but their activities were highly reduced compared with those of 3 and SW-163A.
Efrapeptin J, a New Down-regulator of the Molecular Chaperone GRP78 from a Marine Tolypocladium sp.
A new down-regulator of the molecular chaperone GRP78, efrapeptin J, was isolated from a marine fungus and elucidated to be a linear pentadecapeptide containing a hexahydropyrrolo[1,2-a]pyrimidinium moiety by NMR and MS analyses.
JBIR-52, a new antimycin-like compound, from Streptomyces sp. ML55
GRP78/Bip is a molecular chaperone in the endoplasmic reticulum (ER) induced by ER stress that promotes protein folding and has an important role as a survival factor in solid tumors by providing
A Total Synthesis of Prunustatin A
A total synthesis of prunustatin A, a GRP78 molecular chaperone down-regulator, has been achieved. The key step in the synthesis is an intramolecular transesterification of the β-keto ester alcohol
Repositioning of Verrucosidin, a Purported Inhibitor of Chaperone Protein GRP78, as an Inhibitor of Mitochondrial Electron Transport Chain Complex I
This study identifies mitochondria as the primary target of VCD, and shows that VCD was highly cytotoxic only under hypoglycemic conditions, but not in the presence of normal glucose levels, and VCD blocked mitochondrial energy production via inhibition of complex I of the electron transport chain.
A Novel Antimycin-like Compound, JBIR-06, from Streptomyces sp. ML55
A novel compound of antimycin family, JBIR-06 (1), was isolated from Streptomyces sp. ML55. The structure of 1 was established as a twelve-membered macrocyclic skeleton with a
Selective cytotoxic activity of valinomycin against HT-29 Human colon carcinoma cells via down-regulation of GRP78.
It is found that valinomycin prevents UPR-induced protein expression, such as GRP78 and GRP94, and results in selective cell death of the stressed cancer cells.
A Novel Versipelostatin Analogue, Versipelostatin F Isolated from Streptomyces versipellis 4083-SVS6
A novel versipelostatin F (2) was isolated from Streptomyces versipellis 4083-SVS6 and inhibited the expression of GRP78 induced by 2-deoxyglucose with an IC50 value of 0.3 μM, which is 10-times more potent compared with that of 1.5 μM.
Rare Streptomyces N-formyl amino-salicylamides inhibit oncogenic K-Ras.
SAR investigations inclusive of the biosynthetically related antimycins and respirantin, and synthetic benzoxazolone, documented a unique N-formyl amino-salicylamide pharmacophore as a potent inhibitor of oncogenic K-Ras.


The structure of neoantimycin.
Effect on tumor cells of blocking survival response to glucose deprivation.
The UPR-inhibitory action of VST was seen only in conditions of glucose deprivation and caused selective and massive killing of the glucose-deprived cells.
The unfolded protein response and Alzheimer's disease.
Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls.
What is presently known about the diversity of molecular signaling mechanisms that coordinate the complex ER stress response at the translational and transcriptional level in yeast and in higher eukaryotic cells is summarized.
Modulation of VP-16 cytotoxicity by carboplatin and 41.8°C hyperthermia
Data taken collectively demonstrate a sequence effect (regarding the aforementioned antineoplastic agents), and provide a framework for future studies directed at the therapeutic optimization of the sequential application of carboplatin, hyperthermia, and VP-16.
Blockade of survival response to glucose deprivation for selective killing of tumor cells
  • J Natl Can Inst
  • 2004
SW‐163A and B, Novel Immunosuppressants Produced by Streptomyces sp.
The total synthesis of a diastereomeric mixture of antimycin A3 (blastmycin).
Latumcidin, a new antibiotic from Streptomyces sp.