title: PepT1, ASBT-Linked Prodrug Strategy to Improve Oral Bioavailability and Tissue Targeting Distribution.
abstract: With the rapid development of molecular biology, various of drug transporters have been discovered in several important organs of the body, which determine intracellular exposure and pharmacokinetic performances of drugs by modulating cellular entry and exit. This article focuses on the design of transporter-linked prodrug to enhance oral bioavailability and to acquire tissue-specific distribution pattern, especially paying attention to peptide transporter 1 (PepT1) and apical sodium dependent bile acid transporter (ASBT). Conjugation of the native promotety to active drug was one of the effective methods to improve membrane permeability and distribution profiles of drugs. In this review, we highlight the transporter-linked prodrug design modality based on PepT1 and ASBT. The biology of transporters, structure-transport relationship, key features of natural substrates and successful examples of transporter-linked prodrugs are overviewed in detail.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Han
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: No. 59 Mailbox, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. hezhgui_student@aliyun.com.
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000284:Administration, Oral; D000818:Animals; D006801:Humans; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D000074011:Peptide Transporter 1; D011355:Prodrugs / Q000493:pharmacokinetics*; D027981:Symporters / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D029363:Organic Anion Transporters, Sodium-Dependent; D000074011:Peptide Transporter 1; D011355:Prodrugs; D027981:Symporters; C071908:sodium-bile acid cotransporter