蛋白酪氨酸磷酸酶SHP2在细胞信号转导过程中起着重要的作用,参与细胞的生长、分化、代谢、运动和凋亡,作为潜在的抗肿瘤治疗靶点备受关注。二芳基甲酮化合物在生物活性分子中广泛存在,是基于片段的药物发现策略(fragment-based drug dis...蛋白酪氨酸磷酸酶SHP2在细胞信号转导过程中起着重要的作用,参与细胞的生长、分化、代谢、运动和凋亡,作为潜在的抗肿瘤治疗靶点备受关注。二芳基甲酮化合物在生物活性分子中广泛存在,是基于片段的药物发现策略(fragment-based drug discovery, FBDD)的理想结构模块。本试验研究了二芳基甲酮化合物在SHP2PTP模型上的构效关系,结果表明4-甲氧基二苯甲酮(1l)、(2-氟苯基)-(2-噻吩基)甲酮(1u)以及(2,4-二甲氧基苯基)-(2-氟苯基)甲酮(1v)在20 μg/mL的浓度下,对SHP2PTP分别表现了53.90% ±8.35%、47.03% ±4.85%和50.08% ±3.90%的抑制率,为后续基于片段的SHP2抑制剂研究工作奠定了一定的基础。展开更多
Ordered mesoporous noble metals(NMs)have displayed unique catalytic and electrocatalytic performance distinctive from traditional nanoparticles.Despite great efforts,the range of mesoporous NMs is mainly limited to si...Ordered mesoporous noble metals(NMs)have displayed unique catalytic and electrocatalytic performance distinctive from traditional nanoparticles.Despite great efforts,the range of mesoporous NMs is mainly limited to single metals and their metal alloys with random atomic arrangements.Herein,we report a simple solid-phase synthesis of novel mesoporous intermetallic noble metal-nonmetal(MI-PtX_(2))nanoparticles with hierarchical orderliness as highly efficient electrocatalysts for hydrogen evolution reaction(HER).The synthesis relies on a Pt-to-PtX_(2) evolution with mesoporous Pt confined in thermally stable KIT-6(Korea Advanced Institute of Science and Technology-6)as the concurrent template.Meanwhile,the method could be extended readily to control structures and compositions of mesoporous intermetallic nanoparticles such as hollow structures and ternary MI-PtMP_(2).Samples featured rhombic dodecahedral morphology,ordered gyroid mesostructure,and cubic/hexagonal intermetallic phase,producing abundant undercoordinated sites and optimized surface electronic structures.These features kinetically accelerate H_(2)O dissociation to remarkably enhance electrocatalytic HER performance.The optimum MI-PtP_(2) disclosed ultrahigh mass/specific activity(3.31 A mg_(pt)^(−1)/7.75 mA cm_(pt)^(−2))and superior stability(only 15.2%of mass activity loss after an accelerated durability test for 30,000 cycles),suppressing the reported electrocatalysts.Our work opens up new opportunities for designing and synthesizing novel hierarchically ordered mesoporous electrocatalysts with targeted functions for a variety of applications.展开更多
Two new 5-alkylpyrrole-2-carboxaldehyde derivatives,mycalenitrile-15（1） and mycalenitrile-16（2）,along with five known related ones（3-7）,were isolated from the South China Sea sponge Mycale lissochela.The structu...Two new 5-alkylpyrrole-2-carboxaldehyde derivatives,mycalenitrile-15（1） and mycalenitrile-16（2）,along with five known related ones（3-7）,were isolated from the South China Sea sponge Mycale lissochela.The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR data with those reported in the literature.In bioassay,compounds 1 and 7 exhibited significant PTPIB（Protein-tyrosine phosphatase 1B,a recognized target for diabetes and obesity） inhibitory activities with IC（50） values of 8.6 and 3.1 μmoI/L,respectively.A preliminary SAR analysis of the isolated compounds with their PTP1 B inhibitory effects was described.展开更多
文摘Ordered mesoporous noble metals(NMs)have displayed unique catalytic and electrocatalytic performance distinctive from traditional nanoparticles.Despite great efforts,the range of mesoporous NMs is mainly limited to single metals and their metal alloys with random atomic arrangements.Herein,we report a simple solid-phase synthesis of novel mesoporous intermetallic noble metal-nonmetal(MI-PtX_(2))nanoparticles with hierarchical orderliness as highly efficient electrocatalysts for hydrogen evolution reaction(HER).The synthesis relies on a Pt-to-PtX_(2) evolution with mesoporous Pt confined in thermally stable KIT-6(Korea Advanced Institute of Science and Technology-6)as the concurrent template.Meanwhile,the method could be extended readily to control structures and compositions of mesoporous intermetallic nanoparticles such as hollow structures and ternary MI-PtMP_(2).Samples featured rhombic dodecahedral morphology,ordered gyroid mesostructure,and cubic/hexagonal intermetallic phase,producing abundant undercoordinated sites and optimized surface electronic structures.These features kinetically accelerate H_(2)O dissociation to remarkably enhance electrocatalytic HER performance.The optimum MI-PtP_(2) disclosed ultrahigh mass/specific activity(3.31 A mg_(pt)^(−1)/7.75 mA cm_(pt)^(−2))and superior stability(only 15.2%of mass activity loss after an accelerated durability test for 30,000 cycles),suppressing the reported electrocatalysts.Our work opens up new opportunities for designing and synthesizing novel hierarchically ordered mesoporous electrocatalysts with targeted functions for a variety of applications.
基金financially supported by the National Natural Science Foundation of China(Nos.41476063,81520108028,81273430,41306130 81302692,41676073,81603022)SCTSM Project from Shanghai Science and Technology Committee,Shanghai,China(Nos.14431901100,15431901000)+4 种基金The project from Institutes for Drug Discovery and Development,Chinese Academy of Sciences,China(No.CASIMM0120152039)the SKLDR/SIMM Projects from Shanghai Institute of MateriaMedica,China(No.SIMM 1501ZZ-03)support of "Youth Innovation Promotion Association"(No.2016258) from Chinese Academy of Sciences"Young Talent Supporting Project" from China Association for Science and Technology(No.2016QNRC001)Shanghai "Pujiang Program"(No.16PJ1410600)
文摘Two new 5-alkylpyrrole-2-carboxaldehyde derivatives,mycalenitrile-15（1） and mycalenitrile-16（2）,along with five known related ones（3-7）,were isolated from the South China Sea sponge Mycale lissochela.The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR data with those reported in the literature.In bioassay,compounds 1 and 7 exhibited significant PTPIB（Protein-tyrosine phosphatase 1B,a recognized target for diabetes and obesity） inhibitory activities with IC（50） values of 8.6 and 3.1 μmoI/L,respectively.A preliminary SAR analysis of the isolated compounds with their PTP1 B inhibitory effects was described.
