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OUR APPROACH Xtal's approach is a comprehensive 360 degree look at all the various factors that play into the effective assessment of a candidate's potential in-vivo efficacy and intended/unintended action(s). Classic approaches have focused one or two dimensionally on attempting to ascertain the candidate's efficacy. To push a candidate through even the first one or two phases of trials is a tremendous undertaking that can literally be the factor for wholesale failure of not just the candidate but the entire company and its other candidate's. At the very least, it can severely compromise business strategy and lead to loss of equity. Risk is endemic at every turn. All available methodologies and resources must be pooled and applied in logical steps and at key moments in the cycle to realize the most efficient yet thorough analysis of the candidate. Only through this approach, we believe, can you obtain the best critical intelligence to continue development or quickly change strategy and resource allocation. This risk mitigation is one of the key and overarching benefits behind our comprehensive 360 degree approach. We don't believe in giving you one or two dimensional analysis. We integrate into your business goals and create a custom analytic pathway that is dynamic and thorough without being redundant or wasteful. SAMPLE SCENARIOS Example 1: In a lot of cases drugs that pass Phase I, too often fail to show efficacy in later stages of trials, or prove too narrow in scope. Xtal has the ability to work with various cell lines and disease models to check for cross reactivity and improve the broad target list. If the narrow mode of binding is preferable we can help in creating a library of very potent analogues that will help broaden the effectiveness. Example II: The suggestion of a simple ITC characterization of the protein and ligand to confirm an initial cell based assay result prior to moving onto co-crystalization. This simple step can assure that the protein target discovered in the initial assay is indeed correct before moving onto to the more intensive co-crystalization step that gives our clients the confidence they need to move on and the risk mitigation that assures efficient development. Example III: Hardware and software advances in mass spectrometry now allow us to analyze phosphorylation states of proteins of interest quickly and more efficiently than ever before. We can now use this device to judge the addition of a phosphate group to the overall mass of the protein thereby allowing us to easily identify activation of certain proteins in relation to results produced via cell based assays. This same technique can also be applied to other questions about molecules of interest. Example IV: Structure guided drug discovery is via X-ray crystallography is a common and often used technology for predicting ligand to receptor binding affinity. But we have also provided structural information for the receptors themselves, deglycosilation sites, and multi-protein complexes in an effort to understand the biology and the biological implications of a particular thought process the client had. |
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