Transporters are membrane proteins mediating permeation of organic and inorganic solutes through the plasma membrane and membranes of intracellular organella.They play essential roles in the epithelial absorption and ...Transporters are membrane proteins mediating permeation of organic and inorganic solutes through the plasma membrane and membranes of intracellular organella.They play essential roles in the epithelial absorption and cellular uptake of nutrients as well as absorption,distribution,metabolism,and excretion of drugs.Because transporters contribute to determining the distribution of compounds in the body in concert with metabolic/synthetic enzymes,the drugs that affect the functions of transporters are expected to alter the distribution of compounds in the body and to ameliorate disrupted homeostasis.In this context,drugs targeting transporters have been used clinically.Such drugs include antidepressants targeting monoamine transporters,diuretics targeting inorganic ion transporters of renal tubules,and uricosuric agents targeting renal urate transporters.Now new transporter-targeting drugs designed based on post-genome drug development strategy have been in the process of clinical trials or basic/clinical researches.For example,the inhibitors of renal Na+/glucose cotransporter SGLT2 have been proved for their efficacy in the treatment of diabetes mellitus.The cancer L-type amino acid transporter 1(LAT1) has been considered as a target of cancer diagnosis and therapeutics.The transporter-targeting drugs are expected to provide new rationale in the therapeutics of various diseases.展开更多
基金Culture,Sports,Science,and Technology of JapanGrants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science+1 种基金Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT)A Grant-in-Aid for Scientific Research on Priority Areas of "Transportsome" from the Ministry of Education,Chinese Ministry of Sciences and Technology Research Grant (2009ZX09304-002)
文摘Transporters are membrane proteins mediating permeation of organic and inorganic solutes through the plasma membrane and membranes of intracellular organella.They play essential roles in the epithelial absorption and cellular uptake of nutrients as well as absorption,distribution,metabolism,and excretion of drugs.Because transporters contribute to determining the distribution of compounds in the body in concert with metabolic/synthetic enzymes,the drugs that affect the functions of transporters are expected to alter the distribution of compounds in the body and to ameliorate disrupted homeostasis.In this context,drugs targeting transporters have been used clinically.Such drugs include antidepressants targeting monoamine transporters,diuretics targeting inorganic ion transporters of renal tubules,and uricosuric agents targeting renal urate transporters.Now new transporter-targeting drugs designed based on post-genome drug development strategy have been in the process of clinical trials or basic/clinical researches.For example,the inhibitors of renal Na+/glucose cotransporter SGLT2 have been proved for their efficacy in the treatment of diabetes mellitus.The cancer L-type amino acid transporter 1(LAT1) has been considered as a target of cancer diagnosis and therapeutics.The transporter-targeting drugs are expected to provide new rationale in the therapeutics of various diseases.
