Authors: | Kuduk, S. D.; Zheng, F. F.; Sepp-Lorenzino, L.; Rosen, N.; Danishefsky, S. J. |
Article Title: | Synthesis and evaluation of geldanamycin-estradiol hybrids |
Abstract: | Geldanamycin (GDM) binds to the Hsp90 chaperone protein and causes the degradation of several important signalling proteins. A series of novel estradiol-geldanamycin hybrids has been synthesized and evaluated for their ability to induce the selective degradation of the estrogen receptor (ER). The hybrid compounds are active and more selective than the parent causing degradation of ER and HER2, but not other GDM targets. |
Keywords: | protein degradation; protein targeting; protein binding; drug structure; tumor cells, cultured; drug synthesis; enzyme inhibitors; hsp90 heat-shock proteins; quinones; down regulation; receptors, estrogen; estrogen receptor; inhibitory concentration 50; estradiol; reaction analysis; models, chemical; chemical reaction; benzoquinones; lactams, macrocyclic; geldanamycin; chaperone; hybridization; humans; article; streptomyces hygroscopicus |
Journal Title: | Bioorganic & Medicinal Chemistry Letters |
Volume: | 9 |
Issue: | 9 |
ISSN: | 0960-894X |
Publisher: | Pergamon-Elsevier Science Ltd |
Date Published: | 1999-05-03 |
Start Page: | 1233 |
End Page: | 1238 |
Language: | English |
DOI: | 10.1016/s0960-894x(99)00185-7 |
PUBMED: | 10340605 |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |