期刊
NATURE CHEMICAL BIOLOGY
卷 12, 期 4, 页码 218-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.2016
关键词
-
资金
- Clayton Foundation for Research
- US National Institutes of Health [HL20948]
- Cancer Prevention Research Institute of Texas (CPRIT) [RP120613]
- Simmons Cancer Center (National Cancer Institute) [1P30CA142543-01]
- CPRIT [RP110708-C2, RP110708-C3, RP110708-P3]
- CTD2 [1 U01 CA176284-01]
- Welch Foundation [I-1612]
- Disease Oriented Clinical Scholar (DOCS) award
- Presidential Research Council (PRC) award
- Damon Runyon Clinical Investigator Award [CI-68-13]
A hallmark of targeted cancer therapies is selective toxicity among cancer cell lines. We evaluated results from a viability screen of over 200,000 small molecules to identify two chemical series, oxalamides and benzothiazoles, that were selectively toxic at low nanomolar concentrations to the same 4 of 12 human lung cancer cell lines. Sensitive cell lines expressed cytochrome P450 (CYP) 4F11, which metabolized the compounds into irreversible inhibitors of stearoyl CoA desaturase (SCD). SCD is recognized as a promising biological target in cancer and metabolic disease. However, SCD is essential to sebocytes, and accordingly SCD inhibitors cause skin toxicity. Mouse sebocytes did not activate the benzothiazoles or oxalamides into SCD inhibitors, providing a therapeutic window for inhibiting SCD in vivo. We thus offer a strategy to target SCD in cancer by taking advantage of high CYP expression in a subset of tumors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据