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      Challenges of antibacterial discovery.

      1
      Clinical microbiology reviews
      American Society for Microbiology

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          Abstract

          The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.

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          Author and article information

          Journal
          Clin Microbiol Rev
          Clinical microbiology reviews
          American Society for Microbiology
          1098-6618
          0893-8512
          Jan 2011
          : 24
          : 1
          Affiliations
          [1 ] LL Silver Consulting, LLC, 955 S. Springfield Ave., Unit C403, Springfield, NJ 07081, USA. silverly@comcast.net
          Article
          24/1/71
          10.1128/CMR.00030-10
          3021209
          21233508
          b62c0f14-53e1-41fb-abe1-4f22ee6a8c09
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