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| 1 | Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC)is an aggressive human cancer with increasing incidence worldwide.Multiple efforts have been made to explore pharmaceutical therapies to treat HCC,such as targeted tyrosine kinase inhibitors,immune based therapies and combination of chemotherapy.However,limitations exist in current strategies including chemoresistance for instance.Tumor initiation and progression is driven by reprogramming of metabolism,in particular during HCC development.Recently,metabolic associated fatty liver disease(MAFLD),a reappraisal of new nomenclature for nonalcoholic fatty liver disease(NAFLD),indicates growing appreciation of metabolism in the pathogenesis of liver disease,including HCC,thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment.In this review,we introduce directions by highlighting the metabolic targets in glucose,fatty acid,amino acid and glutamine metabolism,which are suitable for HCC pharmaceutical intervention.We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment.Furthermore,opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed. | Danyu Du Chan Liu Mengyao Qin Xiao Zhang Tao Xi Shengtao Yuan Haiping Hao Jing Xiong | 2022 | Acta Pharmaceutica Sinica B2022，12，2： | 27 |
| 2 | Preclinical efficacy against acute myeloid leukaemia of SH1573, a novel mutant IDH2 inhibitor approved for clinical trials in China显示文摘Acute myeloid leukaemia(AML) is the most common form of acute leukaemia in adults,with increasing incidence with age and a generally poor prognosis.Almost 20% of AML patients express mutant isocitrate dehydrogenase 2(mIDH2),which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate(2-HG),resulting in poor prognosis.Thus,global institutions have been working to develop mIDH2 inhibitors.SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised.We have conducted a comprehensive study on its pharmacodynamics,pharmacokinetics and safety.First,SH1573 exhibited a strong selective inhibition of mIDH2 R140 Q protein,which could effectively reduce the production of 2-HG in cell lines,serum and tumors of an animal model.It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models.Then,it was confirmed that SH1573 possessed characteristics of high bioavailability,good metabolic stability and wide tissue distribution.Finally,toxicological data showed that SH1573 had no effects on the respiratory system,cardiovascular system and nervous system,and was genetically safe.This research successfully promoted the approval of SH1573 for clinical trials(CTR20200247).All experiments demonstrated that,as a potential drug against mIDH2 R140 Q acute myeloid leukaemia,SH1573 was effective and safe. | Zhiqiang Wang Zhibo Zhang Yong Li Li Sun Dezhen Peng Danyu Du Xian Zhang Luwei Han Liwen Zhao Ligong Lu Hongzhi Du Shengtao Yuan Meixiao Zhan | 2021 | Acta Pharmaceutica Sinica B2021，11，6： | 3 |
| 3 | The Pythium periplocum elicitin PpEli2 confers broad-spectrum disease resistance by triggering a novel receptor-dependent immune pathway in plants显示文摘Elicitins are microbe-associated molecular patterns produced by oomycetes to elicit plant defense.It is still unclear whether elicitins derived from non-pathogenic oomycetes can be used as bioactive molecules for disease control.Here,for the first time we identify and characterize an elicitin named PpEli2 from the soil-borne oomycete Pythium periplocum,which is a non-pathogenic mycoparasite colonizing the root ecosystem of diverse plant species.Perceived by a novel cell surface receptor-like protein,REli,that is conserved in various plants(e.g.tomato,pepper,soybean),PpEli2 can induce hypersensitive response cell death and an immunity response in Nicotiana benthamiana.Meanwhile,PpEli2 enhances the interaction between REli and its co-receptor BAK1.The receptor-dependent immune response triggered by PpEli2 is able to protect various plant species against Phytophthora and fungal infections.Collectively,our work reveals the potential agricultural application of non-pathogenic elicitins and their receptors in conferring broad-spectrum resistance for plant protection. | Kun Yang Yi Wang Jialu Li Yaxin Du Ying Zhai Dong Liang Danyu Shen Rui Ji Xuexiang Ren Hao Peng Maofeng Jing Daolong Dou | 2023 | Horticulture Research2023，10，2： | 0 |
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