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Mark Schnute to Speak at Protein Kinases Drug Design October 24-25 in San Diego - Mark Schnute, Associate Research Fellow at Pfizer To Give a Presentation at the 2nd Protein Kinases & Drug Design Conference - GTCbio.com
Mark Schnute to Speak at Protein Kinases Drug Design October 24-25 in San Diego

 

NewswireToday - /newswire/ - Monrovia, CA, United States, 2013/09/05 - Mark Schnute, Associate Research Fellow at Pfizer To Give a Presentation at the 2nd Protein Kinases & Drug Design Conference - GTCbio.com.

   
 
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Mark Schnute, Associate Research Fellow at Pfizer will give a presentation on “Targeted Covalent-Reversible Inhibitors of Bruton’s Tyrosine Kinase for the Treatment of Autoimmune Disease” at the 2nd Protein Kinases & Drug Design Conference to be held in San Diego, CA on October 24-25, 2013 by GTC.

Targeting of non-catalytic cysteine residues with covalent inhibitors is a powerful strategy for optimizing pharmacologic potency and selectivity on challenging targets such as protein kinases. Nonetheless, concerns over off-target modification of proteins by irreversible covalent inhibitors leading to idiosyncratic toxicity has led to caution in applying this strategy to chronic diseases such as inflammation and autoimmune indication even though these events are rare. The utilization of covalent inhibitors that reversibly form an adduct with the protein cysteine is attractive as they may provide the pharmacodynamic and selectivity benefit with less propensity to form long-lived protein adducts.

Dr. Schnute’s this presentation will describe a strategy to design, optimize and characterize covalent, reversible inhibitors targeting Bruton’s Tyrosine Kinase (Btk) and demonstrate their potential utility towards the treatment of inflammatory and autoimmune diseases. Structure-based drug design was utilized to optimize non-covalent inhibitor contacts within the kinase and guide placement of the covalent reactive group. Subsequent tuning of the reactivity and specificity of the electrophile resulted in the discovery of a class of highly selective Btk inhibitors within the cysteine homolog family. Through this strategy, it was identified that an orally bioavailable, potent and selective small molecule inhibitor of Btk which forms a covalent but reversible adduct with the enzyme as confirmed through enzymology, co-crystal structure analysis and mass spectroscopic characterization. The Btk inhibitor has been shown to be efficacious in several preclinical animal models of arthritis and autoimmune disease. This compound represents a new class of covalent Btk inhibitors which offers promise as a clinical candidate for the treatment of autoimmune and inflammatory diseases.

Kinases, key drivers of malignant transformation and major contributors to a variety of other human pathologies, have emerged as some of the most exciting targets in drug discovery. However, with initial well documented success stories came realization that many hurdles lie in the path of successful development of new drugs, targeting kinase signaling. GTC’s 2nd Protein Kinases & Drug Design Conference (gtcbio.com) will bring together speakers representing world leading academic centers and pharmaceutical companies to discuss how to overcome the many hurdles and answer exciting key questions.

This conference is part of our Protein Discovery Summit 2013, which includes three additional parallel conferences shown below:

• Protein Kinases & Drug Design;
• Protein-Protein Interaction;
• Antibody & Protein Therapeutics;
• Protein Expression, Purification & Characterization.

 
 
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Mark Schnute to Speak at Protein Kinases Drug Design October 24-25 in San Diego

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