s9, a novel anticancer agent, exerts its anti-proliferative activity by interfering with both pi3k-akt-mtor signaling and microtubule cytoskeletons9,一种抗癌剂,对其anti-proliferative活动通过干扰pi3k-akt-mtor信号和微管细胞骨架.pdfVIP
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s9, a novel anticancer agent, exerts its anti-proliferative activity by interfering with both pi3k-akt-mtor signaling and microtubule cytoskeletons9,一种抗癌剂,对其anti-proliferative活动通过干扰pi3k-akt-mtor信号和微管细胞骨架
S9, a Novel Anticancer Agent, Exerts Its Anti-Proliferative
Activity by Interfering with Both PI3K-Akt-mTOR
Signaling and Microtubule Cytoskeleton
1. 1. 2 2 3 3 2
Chao Zhang , Na Yang , Chun-hao Yang , Hua-sheng Ding , Cheng Luo , Yu Zhang , Mao-jiang Wu ,
1 3,4 3,4 1 1
Xiong-wen Zhang , Xu Shen , Hua-liang Jiang , Ling-hua Meng *, Jian Ding *
1 Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China,
2 Division of Organic Synthesis, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China, 3 Drug Discovery and Design Center, Shanghai
Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China, 4 School of Pharmacy, East China University of Science and Technology, Shanghai, China
Abstract
Background: Deregulation of the phosphatidylinositol 3-kinases (PI3K)/Akt/mammalian target of rapamycin (mTOR)
pathway plays a central role in tumor formation and progression, providing validated targets for cancer therapy. S9, a hybrid
of a-methylene-c-lactone and 2-phenyl indole compound, possessed potent activity against this pathway.
Methodology/Principal Findings: Effects of S9 on PI3K-Akt-mTOR pathway were determined by Western blot,
immunofluorescence staining and in vitro kinas assay. The interactions between tubulin and S9 were investigated by
polymerization assay, CD, and SPR assay. The potential binding modes between S9 and PI3K, mTOR or tubulin were
analyz
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