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Proteasome inhibition and its therapeutic potential in multiple myeloma.

Chari A, Mazumder A, Jagannath S - Biologics (2010)

Bottom Line: Due to an unmet clinical need for treatment, the first in class proteasome inhibitor, bortezomib, moved from drug discovery to FDA approval in multiple myeloma in an unprecedented eight years.In the wake of this rapid approval arose a large number of questions about its mechanism of action and toxicity as well as its ultimate role in the treatment of this disease.We conclude with our current understanding of the mechanism of action of this agent and a discussion of the novel proteasome inhibitors under development, as it will be progress in these areas that will ultimately determine the true potential of proteasome inhibition in myeloma.

View Article: PubMed Central - PubMed

Affiliation: Mount Sinai School of Medicine, New York, NY, USA.

ABSTRACT
Due to an unmet clinical need for treatment, the first in class proteasome inhibitor, bortezomib, moved from drug discovery to FDA approval in multiple myeloma in an unprecedented eight years. In the wake of this rapid approval arose a large number of questions about its mechanism of action and toxicity as well as its ultimate role in the treatment of this disease. In this article, we briefly review the preclinical and clinical development of the drug as the underpinning for a systematic review of the large number of clinical trials that are beginning to shed some light on the full therapeutic potential of bortezomib in myeloma. We conclude with our current understanding of the mechanism of action of this agent and a discussion of the novel proteasome inhibitors under development, as it will be progress in these areas that will ultimately determine the true potential of proteasome inhibition in myeloma.

No MeSH data available.


Related in: MedlinePlus

Chemical structure of bortezomib.
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f2-btt-4-273: Chemical structure of bortezomib.

Mentions: In 1993, the company Myogenics was founded by Alfred Goldberg to decrease muscle wasting/cachexia by inhibiting the ubiquitin–proteasome pathway. A team of enzymologists created the first inhibitors of the proteasome: peptide aldehyde analogs of the proteasome’s chymotrypsin-like substrates. Chemists then created a dipeptide boronic acid analog that would eventually come to be known as bortezomib (Figure 2).3


Proteasome inhibition and its therapeutic potential in multiple myeloma.

Chari A, Mazumder A, Jagannath S - Biologics (2010)

Chemical structure of bortezomib.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2990320&req=5

f2-btt-4-273: Chemical structure of bortezomib.
Mentions: In 1993, the company Myogenics was founded by Alfred Goldberg to decrease muscle wasting/cachexia by inhibiting the ubiquitin–proteasome pathway. A team of enzymologists created the first inhibitors of the proteasome: peptide aldehyde analogs of the proteasome’s chymotrypsin-like substrates. Chemists then created a dipeptide boronic acid analog that would eventually come to be known as bortezomib (Figure 2).3

Bottom Line: Due to an unmet clinical need for treatment, the first in class proteasome inhibitor, bortezomib, moved from drug discovery to FDA approval in multiple myeloma in an unprecedented eight years.In the wake of this rapid approval arose a large number of questions about its mechanism of action and toxicity as well as its ultimate role in the treatment of this disease.We conclude with our current understanding of the mechanism of action of this agent and a discussion of the novel proteasome inhibitors under development, as it will be progress in these areas that will ultimately determine the true potential of proteasome inhibition in myeloma.

View Article: PubMed Central - PubMed

Affiliation: Mount Sinai School of Medicine, New York, NY, USA.

ABSTRACT
Due to an unmet clinical need for treatment, the first in class proteasome inhibitor, bortezomib, moved from drug discovery to FDA approval in multiple myeloma in an unprecedented eight years. In the wake of this rapid approval arose a large number of questions about its mechanism of action and toxicity as well as its ultimate role in the treatment of this disease. In this article, we briefly review the preclinical and clinical development of the drug as the underpinning for a systematic review of the large number of clinical trials that are beginning to shed some light on the full therapeutic potential of bortezomib in myeloma. We conclude with our current understanding of the mechanism of action of this agent and a discussion of the novel proteasome inhibitors under development, as it will be progress in these areas that will ultimately determine the true potential of proteasome inhibition in myeloma.

No MeSH data available.


Related in: MedlinePlus