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Molecular Profiles - Articles and news items

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Conformational Bias: A key concept for protein kinase inhibition

Drug Targets, Issue 1 2012 / 28 February 2012 / Henrik Möbitz, Global Discovery Chemistry, Computer Aided Drug Design, Novartis Institutes for Biomedical Research and Doriano Fabbro, Expertise Platform Kinases, Novartis Institutes for Biomedical Research

Protein kinases act as molecular switches with remarkable plasticity and dynamics upon interaction with specific regulatory domains as well as modulators. Conformation provides a conceptual framework for understanding many aspects of kinase biology. The kinase domain has precise structural prerequisites for signal transfer and can oscillate between two major conformations: an on state with maximal kinase activity (active kinase) and an off state with minimal activity on the other extreme. Conformational bias, i.e. a shift in the equilibrium between active and inactive conformations is a key determinant in kinase regulation and can be brought about by many factors including post-translational modifications, regulatory proteins, ligand binding etc. Kinase inhibitors can be viewed as particular ligands to protein kinases. As the mode of action is linked to the binding mode, the selectivity as well as the kinetics of kinase inhibitors can often be rationalised based on the target conformation. Pathologic kinase deregulation often involves a shift towards the active conformation, leading to constitutive signalling. In this review, we discuss how mutations act as a conformational bias and depending on the mode of action can lead to activation of the protein kinase that can either result in resistance or contribute to the efficacy of kinase inhibitors. Deregulation of protein kinase activities by mutations and/or amplification are associated with a variety of pathologies ranging from cancer to inflammatory diseases, diabetes, infectious diseases and cardiovascular and metabolic disorders…

Nikin Patel, Molecular Profiles

CEO of Molecular Profiles recognized as one of 100 most inspiring people in the life sciences industry

News, Supplier news / 5 August 2011 / The Scott Partnership

Nikin Patel, acknowledged as one of the top 100 most inspiring individuals…

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Molecular Profiles’ innovative drug development services win Queen’s Award for Enterprise 2011

News, Supplier news / 21 April 2011 / The Scott Partnership

Molecular Profiles awarded Queen’s Award for its nanoPASST service platform…

Molecular Profiles installs Xcelodose system to speed drug development

News, Supplier news / 8 February 2011 / The Scott Partnership

Molecular Profiles, continues expansion of its manufacturing capabilities with the recent purchase of the Xcelodose 120S system…

Molecular Profiles expands offering with new manufacturing capabilities

News, Supplier news / 17 January 2011 / The Scott Partnership

Expansion enables them to handle larger projects from preformulation through to Phase IIa…

Molecular Profiles Unveils New Capabilities at AAPS 2010

News, Supplier news / 2 November 2010 / The Scott Partnership

Molecular Profiles announces it is to demonstrate its expansion of capabilities at the upcoming AAPS / FIP Pharmaceutical Sciences World Congress 2010, booth # 712…

 

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