Trust Your Gut: Strategies and Tactics for Intestinally Restricted Drugs

被引：0
作者：
Dorel, Ruth [1 ]
Wong, Alice R. [1 ]
Crawford, James J. [1 ]
机构：
[1] Genentech Inc, South San Francisco, CA 94080 USA
来源：
ACS MEDICINAL CHEMISTRY LETTERS | 2023年
关键词：
tissue targeting; gut restriction; low absorption; local concentration; small-molecule drugs;
D O I：
暂无
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Non-absorbable small-molecule drugs targeted to the gut represent an alternative approach to safe, non-systemic therapeutics. Such drugs remain confined to the gastrointestinal tract upon oral dosing by virtue of their limited passive permeability, increasing the local concentration at the site of action while minimizing exposure elsewhere in the body. Herein we review the latest advances in the field of gut-restricted therapeutics, highlighting the different strategies and tactics that medicinal chemists have employed in pursuit of drugs with minimal intestinal absorption.
引用
收藏
页数：11
相关论文
共 77 条
  • [1] Advances in Oral Drug Delivery
    Alqahtani, Mohammed S.
    Kazi, Mohsin
    Alsenaidy, Mohammad A.
    Ahmad, Muhammad Z.
    [J]. FRONTIERS IN PHARMACOLOGY, 2021, 12
  • [2] Colon-Targeted Oral Drug Delivery Systems: Design Trends and Approaches
    Amidon, Seth
    Brown, Jack E.
    Dave, Vivek S.
    [J]. AAPS PHARMSCITECH, 2015, 16 (04): : 731 - 741
  • [3] Caco-2 monolayers in experimental and theoretical predictions of drug transport (Reprinted from Advanced Drug Delivery Reviews, vol 22, pg 67-84, 1996)
    Artursson, P
    Palm, K
    Luthman, K
    [J]. ADVANCED DRUG DELIVERY REVIEWS, 2001, 46 (1-3) : 27 - 43
  • [4] Optimizing Oral Bioavailability in Drug Discovery: An Overview of Design and Testing Strategies and Formulation Options
    Aungst, Bruce J.
    [J]. JOURNAL OF PHARMACEUTICAL SCIENCES, 2017, 106 (04) : 921 - 929
  • [5] Intestinally-restricted Janus Kinase inhibition: a potential approach to maximize the therapeutic index in inflammatory bowel disease therapy
    Beattie, David T.
    Pulido-Rios, M. Teresa
    Shen, Fei
    Ho, Melissa
    Situ, Eva
    Tsuruda, Pam R.
    Brassil, Patrick
    Kleinschek, Melanie
    Hegde, Sharath
    [J]. JOURNAL OF INFLAMMATION-LONDON, 2017, 14
  • [6] Soft drugs: design principles, success stories, and future perspectives
    Buchwald, Peter
    [J]. EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2020, 16 (08) : 645 - 650
  • [7] Features of ZED1227: The First-In-Class Tissue Transglutaminase Inhibitor Undergoing Clinical Evaluation for the Treatment of Celiac Disease
    Buechold, Christian
    Hils, Martin
    Gerlach, Uwe
    Weber, Johannes
    Pelzer, Christiane
    Heil, Andreas
    Aeschlimann, Daniel
    Pasternack, Ralf
    [J]. CELLS, 2022, 11 (10)
  • [8] Intestinally-targeted TGR5 agonists equipped with quaternary ammonium have an improved hypoglycemic effect and reduced gallbladder filling effect
    Cao, Hua
    Chen, Zhi-Xiang
    Wang, Kai
    Ning, Meng-Meng
    Zou, Qing-An
    Feng, Ying
    Ye, Yang-Liang
    Leng, Ying
    Shen, Jian-Hua
    [J]. SCIENTIFIC REPORTS, 2016, 6
  • [9] An N,N-Bis(benzimidazolylpicolinoyl)piperazine (BT-11): A Novel Lanthionine Synthetase C-Like 2-Based Therapeutic for Inflammatory Bowel Disease
    Carbo, Adria
    Gandour, Richard D.
    Hontecillas, Raquel
    Philipson, Noah
    Uren, Aykut
    Bassaganya-Riera, Josep
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (22) : 10113 - 10126
  • [10] Non-Systemic Drugs: A Critical Review
    Charmot, Dominique
    [J]. CURRENT PHARMACEUTICAL DESIGN, 2012, 18 (10) : 1434 - 1445
12345678