Target discovery,involving target identification and validation,is the prerequisite for drug discovery and screening.Novel methodologies and technologies for the precise discovery and confirmation of drug targets are ...Target discovery,involving target identification and validation,is the prerequisite for drug discovery and screening.Novel methodologies and technologies for the precise discovery and confirmation of drug targets are powerful tools in understanding the disease,looking for a drug and elucidating the mechanism of drug treatment.Among the common target identification and confirmation methods,the modified method is time-consuming and laborious,which may reduce or change the activity of natural products.The unmodified methods developed in recent years without chemical modification have gradually become an important means of studying drug targets.A wide range of unmodified approaches have been reported,introducing and analyzing the recent emerging methodologies and technologies.This review highlights the advantages and limitations of these methods for the application of drug target discovery and presents an overview of their contributions to the target discovery of small molecule drugs.The application and future development trends of methodologies in target discovery are also prospected to provide a reference for drug target research.展开更多
Rational design and exploitation of nanomaterials with superior treatment properties for suitable indications is a way out to relieve cost constraint of therapy and solve the unsatisfactory efficacy for cancer patient...Rational design and exploitation of nanomaterials with superior treatment properties for suitable indications is a way out to relieve cost constraint of therapy and solve the unsatisfactory efficacy for cancer patients.In this work,we propose a greatly facile approach to produce heterogeneous Pd-Au nanorods(Pd-Au NRs)that solve the current bottleneck problems of photothermal thermal therapy(PTT)as well as completely eliminate tumors in animal models without toxic side effects.Depositing Pd clusters on both tips of Au NRs offers Pd-Au NRs three novel functions,i.e.,the extension of the absorption into NIR-Ⅱ region,the activation of prodrug of 5-fluorouracil(5-Fu)via the bioorthogonal reaction,and the peroxidase-mimic activity to produce·OH.The heterogeneous nanorods showed a high and stable photothermal conversion efficiency(52.07%)in a safer NIR-Ⅱ irradiation region(1,064 nm),which not only eliminate most of tumor cells at only one dose of the irradiation for 5 min but also improve the in situ conversion of 5-fluoro-1-propargyluracil and H2O2 into active 5-Fu and·OH to eradicate residual tumors for inhibiting tumor metastasis.This dual catalytic activity-synergistic mechanism of PTT demonstrates the importance of material design in solving current bottleneck problem of tumor therapy.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.31870946)the Funding of Double First-rate discipline construction(No.CPU2018GF07)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Open Project Program of MOE Key Laboratory of Drug Quality Control and Pharmacovigilance(No.DQCP20/21MS01).
文摘Target discovery,involving target identification and validation,is the prerequisite for drug discovery and screening.Novel methodologies and technologies for the precise discovery and confirmation of drug targets are powerful tools in understanding the disease,looking for a drug and elucidating the mechanism of drug treatment.Among the common target identification and confirmation methods,the modified method is time-consuming and laborious,which may reduce or change the activity of natural products.The unmodified methods developed in recent years without chemical modification have gradually become an important means of studying drug targets.A wide range of unmodified approaches have been reported,introducing and analyzing the recent emerging methodologies and technologies.This review highlights the advantages and limitations of these methods for the application of drug target discovery and presents an overview of their contributions to the target discovery of small molecule drugs.The application and future development trends of methodologies in target discovery are also prospected to provide a reference for drug target research.
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.31870946,81421004,52027801,31470916,and 51631001)the Natural Science Foundation of Beijing Municipality(No.2191001)+2 种基金the Funding of Double First-rate discipline construction(No.CPU2018GF07)the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Open Project Program of MOE Key Laboratory of Drug Quality Control and Pharmacovigilance(No.DQCP20/21MS01).
文摘Rational design and exploitation of nanomaterials with superior treatment properties for suitable indications is a way out to relieve cost constraint of therapy and solve the unsatisfactory efficacy for cancer patients.In this work,we propose a greatly facile approach to produce heterogeneous Pd-Au nanorods(Pd-Au NRs)that solve the current bottleneck problems of photothermal thermal therapy(PTT)as well as completely eliminate tumors in animal models without toxic side effects.Depositing Pd clusters on both tips of Au NRs offers Pd-Au NRs three novel functions,i.e.,the extension of the absorption into NIR-Ⅱ region,the activation of prodrug of 5-fluorouracil(5-Fu)via the bioorthogonal reaction,and the peroxidase-mimic activity to produce·OH.The heterogeneous nanorods showed a high and stable photothermal conversion efficiency(52.07%)in a safer NIR-Ⅱ irradiation region(1,064 nm),which not only eliminate most of tumor cells at only one dose of the irradiation for 5 min but also improve the in situ conversion of 5-fluoro-1-propargyluracil and H2O2 into active 5-Fu and·OH to eradicate residual tumors for inhibiting tumor metastasis.This dual catalytic activity-synergistic mechanism of PTT demonstrates the importance of material design in solving current bottleneck problem of tumor therapy.
