Abstract
In HeLa cells the combinatorial knockdown of Bcl-xL and Mcl-1 is sufficient to induce spontaneous apoptosis. Quinoxaline derivatives were screened for the induction of Mcl-1 dependent apoptosis using a cell line without functional Bcl-xL. Quinoxaline urea analog 1h was able to specifically induce apoptosis in an Mcl-1 dependent manner. We demonstrate that even small changes to 1h results in dramatic loss of activity. In addition, 1h and ABT-737 synergistically inhibit cell growth and induce apoptosis. Our results also suggest that 1h could have therapeutic potential against ABT-737 refractory cancer.
Original language | English (US) |
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Pages (from-to) | 2227-2234 |
Number of pages | 8 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 20 |
Issue number | 7 |
DOIs | |
State | Published - Apr 1 2012 |
Keywords
- ABT-737
- Bcl-xL
- Mcl-1
- Quinoxaline
- Structure-activity relationship
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry