The pharmaceutical industry has struggled to provide new drugs for stroke and neurodegenerative disease using classical medicinal chemistry approaches.However there is a disconnect between single molecular targets and...The pharmaceutical industry has struggled to provide new drugs for stroke and neurodegenerative disease using classical medicinal chemistry approaches.However there is a disconnect between single molecular targets and such severe diseases.Life style changes,particularly exercise,and some natural products,may extend life span:but what are the molecular targets?IUPHAR has built a database of the molecular targets within the human genome which is freely available,with gold standard ligands:the IUPHAR/BPS GuidetoPHARMACOLOGY(GtoP)database(see GuideToPharmacology.org).The database is unique containing information reviewed by the >90NC-IUPHAR expert committees with their publications(H-index72).These expert committees consider features beyond the capability of machine-based data trawling,such as what we know and don′t know,variables affecting drug receptor affinity,the crucial challenges of multiple gene products,alternative splicing,epigenetics,allostery,disease and drug ontologies.The database is being actively promoted worldwide by the main pharmacological societies,resulting in a large international user-base.This can now be extended to the molecular targets of natural products.Natural products also markedly affect cellular metabolism and I will also cover how recent human evolution selected certain molecular pathways,allowing metabolomics analysis to develop new directions for the treatment of neurodegenerative disease.IUPHAR can be a partner in developing new therapeutic paradigms,by expert assessmentof complex research areas at clinical and preclinical levels.This is a unique cooperative international initiative.Key words:pharmacology;molecular targets;natural展开更多
文摘The pharmaceutical industry has struggled to provide new drugs for stroke and neurodegenerative disease using classical medicinal chemistry approaches.However there is a disconnect between single molecular targets and such severe diseases.Life style changes,particularly exercise,and some natural products,may extend life span:but what are the molecular targets?IUPHAR has built a database of the molecular targets within the human genome which is freely available,with gold standard ligands:the IUPHAR/BPS GuidetoPHARMACOLOGY(GtoP)database(see GuideToPharmacology.org).The database is unique containing information reviewed by the >90NC-IUPHAR expert committees with their publications(H-index72).These expert committees consider features beyond the capability of machine-based data trawling,such as what we know and don′t know,variables affecting drug receptor affinity,the crucial challenges of multiple gene products,alternative splicing,epigenetics,allostery,disease and drug ontologies.The database is being actively promoted worldwide by the main pharmacological societies,resulting in a large international user-base.This can now be extended to the molecular targets of natural products.Natural products also markedly affect cellular metabolism and I will also cover how recent human evolution selected certain molecular pathways,allowing metabolomics analysis to develop new directions for the treatment of neurodegenerative disease.IUPHAR can be a partner in developing new therapeutic paradigms,by expert assessmentof complex research areas at clinical and preclinical levels.This is a unique cooperative international initiative.Key words:pharmacology;molecular targets;natural
