期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 65, 期 9, 页码 6710-6728出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.2c00004
关键词
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资金
- Science and Technology Commission of Shanghai Municipality [21S11907800]
- National Natural Science Foundation of China [81973160, 81903413]
- Shanghai Science and Technology Committee Rising-Star Program [19QA1407200]
- ECNU Multifunctional Platform for Innovation [011]
Osteosarcoma, a common malignant bone tumor, has seen little progress in treatment and clinical outcomes due to its heterogeneity and high mutation rate. Targeting STAT3 has shown potential as a feasible therapeutic strategy for osteosarcoma.
Osteosarcoma is one of the most common malignantbone tumors. However, the treatment and clinical outcomes ofosteosarcoma have hardly changed over the past three decades due tothe comprehensive heterogeneity and higher rate of mutation ofosteosarcoma. Recent studies have shown that STAT3 has the potentialto suppress the proliferation and metastasis of osteosarcoma. In thisstudy, a novel class of 2-amino-3-cyanothiophene derivatives weredesigned and synthesized to inhibit osteosarcoma by targeting STAT3.Representative compound6fshowed potent antiproliferative effectsagainst osteosarcoma cells, directly bound to the STAT3 SH2 domainwith aKDof 0.46 mu M, and inhibited the phosphorylation of STAT3Y705 in a dose-dependent manner. Furthermore, compound6fpromoted osteosarcoma cell apoptosisin vitroand significantly suppressed the growth and metastasis of osteosarcomain vivo.Thesefindings demonstrate that targeting STAT3 may be a feasible therapeutic strategy for the treatment of metastatic osteosarcoma
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