Abstract
In the past two decades, the identification of commonly mutated oncogenes and tumour suppressor genes has driven an unprecedented growth in our understanding of the genetic basis of human cancer. Although oncogenes can clearly serve as classically defined drug targets whose inactivation by small molecules could place a brake on cancer cell proliferation, the restoration of mutated tumour suppressor gene activity by small molecules might appear on the surface to be unrealistic. However, there is a growing realization that many eukaryotic regulatory proteins are partially unfolded and such intrinsically disordered proteins acquire a folded structure after binding to their biological target. Molecular characterization of the p53 protein has shown that its conformational flexibility and intrinsic thermodynamic instability provide a foundation from which its conformation can be quickly post-translationally modified.
Original language | English |
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Pages (from-to) | 347-55 |
Number of pages | 9 |
Journal | Drug Discovery Today |
Volume | 8 |
Issue number | 8 |
Publication status | Published - 15 Apr 2003 |
Keywords / Materials (for Non-textual outputs)
- Allosteric Regulation
- Antineoplastic Agents
- Cyclin-Dependent Kinase Inhibitor p21
- Cyclins
- Drug Design
- Humans
- Molecular Mimicry
- Mutation
- Neoplasms
- Nuclear Proteins
- Protein Conformation
- Protein Folding
- Proto-Oncogene Proteins
- Proto-Oncogene Proteins c-mdm2
- Transcription, Genetic
- Tumor Suppressor Protein p53