期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 11, 期 5, 页码 686-690出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.9b00553
关键词
sphingolipid; anticancer; KRAS mutant cancer; nutrient transporter; vacuolation
资金
- NSERC
- Chao Family Comprehensive Cancer Center Anti-Cancer Challenge
A synthetic sphingolipid related to a ring constrained hydroxymethyl pyrrolidine analog of FTY720 that was known to starve cancer cells to death was chemically modified to include a series of alkoxy-tethered 3,6-substituted 1,2-pyridazines. These derivatives exhibited excellent antiproliferative activity against eight human cancer cell lines from four different cancer types. A 2.5- to 9-fold reduction in IC50 in these cell lines was observed relative to the lead compound, which lacked the appended heterocycle.
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