The identification of effective drug targets and the development of bioactive molecules are areas of high need in cancer therapy.The phosphatidylinositol transfer protein alpha/beta isoform(PITPα/β)has been reported...The identification of effective drug targets and the development of bioactive molecules are areas of high need in cancer therapy.The phosphatidylinositol transfer protein alpha/beta isoform(PITPα/β)has been reported to play an essential role in integrating phosphoinositide trafficking and lipid metabolism in diverse cellular processes but remains unexplored as a potential target for cancer treatment.Herein,data analysis of clinical cancer samples revealed that PITPα/βexpression is closely correlated with the poor prognosis.Target identification by chemical proteomic methods revealed that microcolin H,a naturally occurring marine lipopeptide,directly binds PITPα/βand displays antiproliferative activity on different types of tumour cell lines.Furthermore,we identified that microcolin H treatment increased the conversion of LC3I to LC3II,accompanied by a reduction of the level of p62 in cancer cells,leading to autophagic cell death.Moreover,microcolin H showed preeminent antitumour efficacy in nude mouse subcutaneous tumour models with low toxicity.Our discoveries revealed that by targeting PITPα/β,microcolin H induced autophagic cell death in tumours with efficient anti-proliferating activity,which sheds light on PITPα/βas a promising therapeutic target for cancer treatment.展开更多
A catalytic asymmetric hydroxylative dearomatization reaction has been disclosed,and the products can smoothly transform into spiroannulation adducts by simply treated with a base under mild conditions.Novel in-situ g...A catalytic asymmetric hydroxylative dearomatization reaction has been disclosed,and the products can smoothly transform into spiroannulation adducts by simply treated with a base under mild conditions.Novel in-situ generated magnesium catalytic methods are developed by application of combinational ligands.Related concise transformaitons of the spiroannulation adducts have been carried out.展开更多
基金supported by the Program for the Ministry of Education“Peptide Drugs”Innovation Team(No.IRT_15R27,China)the National Natural Science Foundation of China(21807053)+1 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.2019-I2M-5-074,2021-I2M-1-026,2021-I2M-3-001,2022-I2M-2-002,China)the Fundamental Research Funds for the Central Universities(No.lzujbky-2023-11,lzujbky-2023-ct02,lzujbky-2023-it19,China).
文摘The identification of effective drug targets and the development of bioactive molecules are areas of high need in cancer therapy.The phosphatidylinositol transfer protein alpha/beta isoform(PITPα/β)has been reported to play an essential role in integrating phosphoinositide trafficking and lipid metabolism in diverse cellular processes but remains unexplored as a potential target for cancer treatment.Herein,data analysis of clinical cancer samples revealed that PITPα/βexpression is closely correlated with the poor prognosis.Target identification by chemical proteomic methods revealed that microcolin H,a naturally occurring marine lipopeptide,directly binds PITPα/βand displays antiproliferative activity on different types of tumour cell lines.Furthermore,we identified that microcolin H treatment increased the conversion of LC3I to LC3II,accompanied by a reduction of the level of p62 in cancer cells,leading to autophagic cell death.Moreover,microcolin H showed preeminent antitumour efficacy in nude mouse subcutaneous tumour models with low toxicity.Our discoveries revealed that by targeting PITPα/β,microcolin H induced autophagic cell death in tumours with efficient anti-proliferating activity,which sheds light on PITPα/βas a promising therapeutic target for cancer treatment.
基金the financial support from the National Natural Science Foundation of China (Nos. 21901092, 21807053)Innovation Fund for Medical Sciences (No. 2019-12M-5-074)+2 种基金Program for Chang-jiang Scholars and Innovative Research Team in University (PCSIRT) (No. IRT_15R27)the Funds for Fundamental Research Creative Groups of Gansu Province (No. 20JR5RA310)the Fundamental Research Funds for the Central Universities (Nos. lzujbky2020-49, 2021-kb21)
文摘A catalytic asymmetric hydroxylative dearomatization reaction has been disclosed,and the products can smoothly transform into spiroannulation adducts by simply treated with a base under mild conditions.Novel in-situ generated magnesium catalytic methods are developed by application of combinational ligands.Related concise transformaitons of the spiroannulation adducts have been carried out.