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中文摘要：
细胞命运决定是一个极其复杂的过程。揭开这些复杂生命过程的奥秘，并最终能动的调控这些过程，一直以来是生物医学研究的重点。过去几年，本项目组以活性小分子化合物为探针，围绕体细胞的重编程、线粒体融合、肿瘤细胞的分化和凋亡、以及WNT，JAK/STAT等重要的细胞信号转导途径开展工作，取得了显著进展。本课题拟在此基础上，以前期获得的小分子探针为工具，拟解决 ①维生素C如何克服重编程过程中表观遗传学障碍；②15-氧代绣线菊内酯调控线粒体融合和WNT信号通路的分子靶点，信号机制；③ Wedelolactone和Luteolin增强JAK/STAT信号的负性调控机制；④腺花素诱导白血病细胞分化的机制及其对其它实体瘤命运决定的效应；⑤酪氨酸激酶抑制剂PX0140下调β-catenin及克服Gleevec耐药的分子机制。通过研究，获得系列国际领先并具有自主知识产权的成果，提升我国在化学生物学领域的研究水平。
结论摘要：
英文主题词chemical biology；cell fate decision；signal transduction；small molecules；
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期刊论文
A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/beta-catenin signaling and colon cancer c
3-Anhydro-6-hydroxy-ophiobolin A, a fungal sesterterpene from Bipolaris oryzae induced autophagy and
17-Hydroxy-jolkinolide B inhibits STAT3 signaling by covalently crosslinking Janus kinases and induc
Luteolin sensitizes the antiproliferative effect of interferon α/β by activation of Janus kinase/sig
A novel sulfonamide agent, MPSP-001, exhibits potent activity against human cancer cells in vitro th
Identification of small molecule activators of the janus kinase/signal transducer and activator of t
Polycomb chromobox 4 enhances migration and pulmonary metastasis of hepatocellular carcinoma cell li
Natural products and their derivatives regulating the janus kinase/signal transducer and activator o
Eriocalyxin B Inhibits STAT3 Signaling by Covalently Targeting STAT3 and Blocking Phosphorylation an
Bigelovin inhibits STAT3 signaling by inactivating JAK2 and induces apoptosis in human cancer cells.
A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mo
Antitumor activity of S116836, a novel tyrosine kinase inhibitor, against imatinib-resistant FIP1L1-
A diterpenoid derivate compound targets selenocysteine of thioredoxin reductases and induces Bax/Bak
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