Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 63, Issue 13, Pages 7243-7251Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.0c00475
Keywords
-
Categories
Funding
- DOD-CDMRP Grant [PC131242]
- NIH [P30 CA023168, R01 GM127656, R35 GM128570]
- CDMRP [PC131242, 672438] Funding Source: Federal RePORTER
Ask authors/readers for more resources
Survivin, a homodimeric member of the Inhibitor of Apoptosis Protein (IAP) family, is required for cancer cell survival and overexpressed in almost all solid tumors. However, targeting survivin has been challenging due to its undruggable nature. Recently, we used a novel approach to target the dimerization interface and identified inhibitors of two scaffolds that can directly bind to and inhibit survivin dimerization. One of the scaffolds, represented by the compound LQZ-7, contains an undesirable labile hydrazone linker and a potentially nonfunctional furazanopyrazine ring that we attempted to eliminate in this study. We found one compound, 7I, that is more active than the parent compound, LQZ-7, and when given orally effectively inhibits xenograft tumor growth and induces survivin loss in tumors. These findings indicate that 7I with a stable linker and a quinoxaline ring can be used as a lead for further optimization of this novel class of survivin inhibitors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available