Journal
CURRENT OPINION IN PHARMACOLOGY
Volume 10, Issue 6, Pages 782-788Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.coph.2010.09.005
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Funding
- National Institutes of Health [R01 LM007688 01A1, GM071714 01A2]
- National Science Foundation [EF 0849803]
- Russian Academy of Sciences
- IUPUI Signature Centers Initiative
- Direct For Biological Sciences
- Emerging Frontiers [0849803] Funding Source: National Science Foundation
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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
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