Phthalimide conjugation as a strategy for in vivo target protein degradation
2015; American Association for the Advancement of Science; Volume: 348; Issue: 6241 Linguagem: Inglês
10.1126/science.aab1433
ISSN1095-9203
AutoresGeorg E. Winter, Dennis L. Buckley, Joshiawa Paulk, Justin M. Roberts, Amanda Souza, Sirano Dhe‐Paganon, James E. Bradner,
Tópico(s)Multiple Myeloma Research and Treatments
ResumoA degrading game plan for cancer therapy Certain classes of proteins that contribute to cancer development are challenging to target therapeutically. Winter et al. devised a chemical strategy that, in principle, permits the selective degradation of any protein of interest. The strategy involves chemically attaching a ligand known to bind the desired protein to another molecule that hijacks an enzyme whose function is to direct proteins to the cell's protein degradation machinery. In a proof-of-concept study, they demonstrated selective degradation of a transcriptional coactivator called bromodomain-containing protein 4 and delayed the progression of leukemia in mice. Science , this issue p. 1376
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