Syringolin B-inspired proteasome inhibitor analogue TIR-203 exhibits enhanced biological activity in multiple myeloma and neuroblastoma

@article{OpokuAnsah2012SyringolinBP,
  title={Syringolin B-inspired proteasome inhibitor analogue TIR-203 exhibits enhanced biological activity in multiple myeloma and neuroblastoma},
  author={John Opoku-Ansah and Tannya R. Ibarra-Rivera and Michael C. Pirrung and Andr{\'e} S. Bachmann},
  journal={Pharmaceutical Biology},
  year={2012},
  volume={50},
  pages={25 - 29}
}
Context: The bacterium Pseudomonas syringae pv. syringae (Pss) is a pathogen of many plant species and causes, for example, brown spot disease in bean plants (Phaseolus vulgaris). Pss excretes the syringolins, natural product molecules that act as a virulence factors and inhibit the proteasome of the host plants. Objective: Proteasome inhibitors belong to an important class of anticancer agents and bortezomib (Velcade®) has been Food and Drug Administration-approved for the treatment of… 
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Syrbactin Structural Analog TIR-199 Blocks Proteasome Activity and Induces Tumor Cell Death*
TLDR
The results suggest that TIR-199 is a potent new proteasome inhibitor with promise for further development into a clinical drug for the treatment of multiple myeloma and other forms of cancer.
Activity enhancement of the synthetic syrbactin proteasome inhibitor hybrid and biological evaluation in tumor cells.
TLDR
The study revealed that the novel synthetic syrbactin compound represents one of the most potent proteasome inhibitors analyzed to date and therefore exhibits promising properties for improved drug development as an anticancer therapeutic.
Substrate-guided optimization of the syringolins yields potent proteasome inhibitors with activity against leukemia cell lines.
Syrbactin proteasome inhibitor TIR-199 overcomes bortezomib chemoresistance and inhibits multiple myeloma tumor growth in vivo.
Rational Design of Selective and Bioactive Inhibitors of the Mycobacterium tuberculosis Proteasome.
TLDR
Selective inhibitors of the Mtb 20S were designed and synthesized on the bases of both its unique substrate preferences and the structures of substrate-mimicking covalent inhibitors of eukaryotic proteasomes called syringolins and do not inhibit the growth of human cell lines in vitro and thus may be starting points for tuberculosis drug development.
Thiasyrbactins Induce Cell Death via Proteasome Inhibition in Multiple Myeloma Cells
TLDR
Results show for the first time the proteasome-targeted biological activity of thiasyrbactins in MM tumor cells.
Proteasome inhibitors: a new perspective for treating autoimmune diseases.
TLDR
The use of proteasome inhibitors in treating autoimmune conditions and, in particular, systemic autoimmune diseases, inflammatory bowel disease, multiple sclerosis and organ-specific autoimmune diseases are reviewed.
Natural product scaffolds as inspiration for the design and synthesis of 20S human proteasome inhibitors
TLDR
The following review discusses the efforts made in the field to isolate and identify natural products as inhibitors of the proteasome and some of the modifications made to natural products in order to discover more potent and selective inhibitors for potential disease treatment.
Synthesis and pharmacology of proteasome inhibitors.
TLDR
The chemical synthesis of these natural products finally provided access to analogues and optimized drugs of which two different classes have been approved for the treatment of malignancies.
Neuroblastoma‐targeted nanoparticles and novel nanotechnology‐based treatment methods
TLDR
In this review, genes and protein products that are beneficial as drug targets in the treatment of neuroblastoma have been discussed and novel drug delivery systems with a focus on liposomes as carriers are discussed.
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References

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