Targeting proteases: successes, failures and future prospects

By B. Turk. Nature reviews. Drug discovery, 2006

1,305 citations recorded by the source corpus.

Subfields: Cancer Research, Hematology, Oncology

View Paper: https://www.semanticscholar.org/paper/aac77c059190fc84de64811becc39f3839508043

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. B. Turk
2. C. López‐Otín
3. M. Hayes
4. S. Bleakley
5. L. Matrisian
6. Stephen P. Jackson

In Hematology

1. M. Hayes
2. S. Bleakley
3. C. López‐Otín
4. L. Matrisian

In Oncology

1. B. Turk
2. C. López‐Otín
3. M. Hayes
4. S. Bleakley
5. L. Matrisian
6. Stephen P. Jackson
7. Yosef Shiloh

Citations in the corpus

• Cleavage Entropy as Quantitative Measure of Protease Specificity (2013, background): “Proteases catalyze cleavage of peptide bonds and are involved in virtually all fundamental cellular processes [1] turning proteases into central drug targets [2].”
• Deubiquitylating enzymes and drug discovery: emerging opportunities (2017, background): “Most peptidases, including many cysteine proteases, recognize a small linear-polypeptide motif and cleave either before or after the peptide bond 213 .”
• Emerging roles of proteases in tumour suppression (2007, background): “Our view of the proteolytic world has expanded considerably after the recognition that beyond their nonspecific functions in protein catabolism, proteases act as processing enzymes that carry out highly selective cleavage of specific substrates and influence cell behaviour, survival and deat”
• The resurgence of covalent drugs (2011, background): “Consequently, selectivity has typically been difficult to achieve, because even relatively weak binding to the active site of an off-target protease within the same family could result in a covalent interaction with the conserved catalytic nucleophile and lead to irreversible inhibitio”
• Successful applications of computer aided drug discovery: moving drugs from concept to the clinic. (2010, background): “Others have demonstrated that numerous potent, serine-protease inhibitors [42] incorporate a serine trap into their architecture and thus it was rationalized that Ser139, which is within the active site of the viral protease [43] may react with conventional electrophiles such as aldehydes, ketones, ”
• Algal Proteins: Extraction, Application, and Challenges Concerning Production (2017, positive): “ACE-I inhibitors have therefore become one of the most commonly studied targets, and with global annual sales exceeding US $6 billion, ACE-I inhibitory drugs can be considered as one of the major protease inhibitor success stories [238].”
• PROSPER: An Integrated Feature-Based Tool for Predicting Protease Substrate Cleavage Sites (2012, background): “Moreover, protease activity is also regulated by co-factors, ligands or other proteins that reversibly bind to proteases in an allosteric manner and finally affect the activity [2,9,10].”
• Cysteine cathepsins: From structure, function and regulation to new frontiers (2011, result): “This is consistent with the recent advances in the field of proteases that led to a new concept, based on proteases as important signaling molecules involved in the controlling mechanisms in many normal and pathological processes [37] [38] [39] .”