Fragment‐based Lead Discovery and Optimization Using X‐Ray Crystallography, Computational Chemistry, and High‐throughput Organic Synthesis

Jeff Blaney; Vicki Nienaber; Stephen K Burley

doi:10.1002/3527608761.ch11

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Book chapter

Fragment‐based Lead Discovery and Optimization Using X‐Ray Crystallography, Computational Chemistry, and High‐throughput Organic Synthesis

Jeff Blaney, Vicki Nienaber and Stephen K Burley

Fragment‐based Approaches in Drug Discovery, pp.215-248

Wiley‐VCH Verlag GmbH & Co. KGaA

07/20/2006

DOI: https://doi.org/10.1002/3527608761.ch11

Abstract

combining crystallographic and biochemical fragment screening

complementary biochemical screening of the SGX fragment library

computational chemistry

crystallographic screening

drug discovery

experimental applications

experimental techniques

fragment library design

fragment optimization using X‐ray crystallography

fragment‐based lead discovery

high‐throughput organic synthesis

SGX structure‐driven fragment‐based lead discovery process

This chapter contains sections titled: Introduction Overview of the SGX Structure‐driven Fragment‐based Lead Discovery Process Fragment Library Design for Crystallographic Screening Considerations for Selecting Fragments SGX Fragment Screening Library Selection Criteria SGX Fragment Screening Library Properties SGX Fragment Screening Library Diversity: Theoretical and Experimental Analyses Crystallographic Screening of the SGX Fragment Library Overview of Crystallographic Screening Obtaining the Initial Target Protein Structure Enabling Targets for Crystallographic Screening Fragment Library Screening at SGX‐CAT Analysis of Fragment Screening Results Factor VIIa Case Study of SGX Fragment Library Screening Complementary Biochemical Screening of the SGX Fragment Library Importance of Combining Crystallographic and Biochemical Fragment Screening Selecting Fragments Hits for Chemical Elaboration Fragment Optimization Spleen Tyrosine Kinase Case Study Fragment Optimization Overview Linear Library Optimization Combinatorial Library Optimization Discussion and Conclusions Postscript: SGX Oncology Lead Generation Program References

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Title: Fragment‐based Lead Discovery and Optimization Using X‐Ray Crystallography, Computational Chemistry, and High‐throughput Organic Synthesis
Creators: Jeff Blaney - SGX Pharmaceuticals, Inc., 10505 Roselle Street, San Diego, CA 92121, USA
Vicki Nienaber - SGX Pharmaceuticals, Inc., 10505 Roselle Street, San Diego, CA 92121, USA
Stephen K Burley - SGX Pharmaceuticals, Inc., 10505 Roselle Street, San Diego, CA 92121, USA
Contributors: Wolfgang Jahnke (null) - Novartis Institutes for Biomedical Research, Novartis Pharma AG, Lichtstrasse, 4002 Basel, Switzerland
Daniel A Erlanson (null) - Sunesis Pharmaceuticals, Inc., 341 Oyster Point Boulevard, South San Francisco, CA 94080, USA
Publication Details: Fragment‐based Approaches in Drug Discovery, pp.215-248
Date published: 07/20/2006
Publisher: Wiley‐VCH Verlag GmbH & Co. KGaA; Weinheim, FRG
Number of pages: 34
Academic Unit: Chemistry and Chemical Biology (SAS); Institute for Quantitative Biomedicine
Language: English
Resource Type: Book chapter
Identifiers: 991031665343204646