Abstract
A novel series of heat shock protein 90 (Hsp90) inhibitors was identified by X-ray crystal analysis of complex structures at solvent-exposed exit pocket C. The 2-amino-pyrrolo[2,3-d]pyrimidine derivatives, 7-deazapurines substituted with a benzyl moiety at C5, showed potent Hsp90 inhibition and broad-spectrum antiproliferative activity against NCI-60 cancer cell lines. The most potent compound, 6a, inhibited Hsp90 with an IC50of 36 nM and showed a submicromolar mean GI50value against NCI-60 cell lines. The interaction of 6a at the ATP-binding pocket of Hsp90 was confirmed by X-ray crystallography and Western blot analysis.
Original language | English |
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Pages (from-to) | 237-241 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 27 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2017 |
Keywords
- Antiproliferative
- Cancer
- Hsp90
- Pyrrolo[2,3-d]pyrimidines
- Structure-based design
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry