Drugs for 'protein clouds': Targeting intrinsically disordered transcription factors

A. Keith Dunker, Vladimir N. Uversky

Research output: Contribution to journalReview article

111 Scopus citations


Transcription factors (TFs) are very attractive but difficult drug targets. The difficulties come from several directions including the binding promiscuity of TFs and the intrinsically disordered nature of their binding sites, which often resemble 'protein clouds'. For a long time the targeting of proteins without defined structures was considered infeasible. Data have now emerged showing that selective blocking of specific interactions of intrinsically disordered TFs with their protein binding partners is possible. Initial hits have been optimized to increase their specificity and affinity. Several strategies have been elaborated for elucidating the mechanisms of blocking of intrinsic disorder-based protein-protein interactions. However, challenges remain in the field of drug development for 'protein clouds'; such development is still in its earliest stage.

Original languageEnglish (US)
Pages (from-to)782-788
Number of pages7
JournalCurrent Opinion in Pharmacology
Issue number6
StatePublished - Dec 1 2010

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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