Chapter_35

Chapter_35 - Biol 4087 Click to edit Master subtitle style...

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Click to edit Master subtitle style Biol 4087
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The “Modern” Approach to Drug Discovery
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Small Molecule and Large Molecule Drug Design “Small Molecule” Drugs Low MW Moderately hydrophobic/hydrophilic Moderately chemical complexity “Biologicals” Peptides/peptidomimetics Engineered enzymes Antisense/RNAi Need help to enter cells!
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The Process of Drug Discovery Lead Identification Optimizatio n Drug Candidate Focused Library Protein Targets Binding Screens Binding Asays Functional Asays Startin g Librar y (millio ns ) Functional Screens Pre- Clinical Discovery Clinical Trials I II III Market Target ID Hit ID Lead Optimisation Target Identification
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“New Tools” for Drug Discovery (1980s and 90s) Combinatorial Chemistry Increased the number of available compounds High Throughput Screening (“HTS”) Increases throughput for testing (robotics, databasing) “It’s a Numbers Game”
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Rational Drug Design = the Opposite of “It’s a Numbers Protein  Structure Design small molecule to “fit” and block active site Voila ! Doesn’t  work!
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Structure-based Drug Design Drug Candidate Focused Library Protein Targets Screens Structure Complex Modeling/ Comp. Binding Asays Functional Asays Protein Structure Target Specific Assay Development And “virtual screening” Lead Identification and Optimisation Your first screen may contain hundreds  or  thousands of compounds,   chosen based on predicted binding
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The Purpose of Structure-Based Prediction is to Reduce the Number of Compounds Screened Without
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Structure of Target >4 million ‘real’ compound structures Binding Surface Massively Parallel Virtual Screening (Dock/Flexx) Drug Profiling Virtual Hits Lead Optimisatio n Low/Medium Throughput Assays ‘Real’ Hits Virtual Librarie s Similarity Searches etc. Virtual Screening
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This note was uploaded on 09/13/2010 for the course BIOL 4087 taught by Professor Waldrop during the Spring '08 term at LSU.

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Chapter_35 - Biol 4087 Click to edit Master subtitle style...

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