期刊
BIOORGANIC CHEMISTRY
卷 95, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2019.103547
关键词
SYK; Inhibitor; Cancer
资金
- National Key Research and Development Program of China [2018YFE0114300]
- National Natural Science Foundation of China [81972882, 81903099]
As the aim to discover orally SYK inhibitors for solid tumor treatment, a series of novel derivatives based on imidazo[1,2-a]pyrazine scaffold were designed, synthesized and evaluated. Structure-activity relationship study of both enzymatic and cellular assays led to the identification of compound 12f. The novel SYK inhibitor 12f showed potent antitumor activity against solid tumors with favorable drug-like properties of lipophilicity and solubility. 12f could induce cell apoptosis of ovarian and lung cancer cell lines. In SKOV3 xenograft mouse model, oral administration of 12f led to significant tumour regression without obvious toxicity. 12f improved the limited response of traditional SYK inhibitors in solid tumors in vitro and in vivo. Taken together, this compound may act as a promising lead compound for further development of new SYK inhibitors for solid tumor therapy.
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