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
  • [11] Design of Gut-Restricted Thiazolidine Agonists of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5)
    Chen, Tao
    Reich, Nicholas William
    Bell, Noah
    Finn, Patricia D.
    Rodriguez, David
    Kohler, Jill
    Kozuka, Kenji
    He, Limin
    Spencer, Andrew G.
    Charmot, Dominique
    Navre, Marc
    Carreras, Christopher W.
    Koo-McCoy, Samantha
    Tabora, Jocelyn
    Caldwell, Jeremy S.
    Jacobs, Jeffrey W.
    Lewis, Jason Gustaf
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2018, 61 (17) : 7589 - 7613
  • [12] Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 12-Week, Placebo-Controlled Phase 3 Trial (T3MPO-1)
    Chey, William D.
    Lembo, Anthony J.
    Rosenbaum, David P.
    [J]. AMERICAN JOURNAL OF GASTROENTEROLOGY, 2020, 115 (02) : 281 - 293
  • [13] COMPUTER-ASSISTED COMPUTATION OF PARTITION-COEFFICIENTS FROM MOLECULAR-STRUCTURES USING FRAGMENT CONSTANTS
    CHOU, JT
    JURS, PC
    [J]. JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1979, 19 (03): : 172 - 178
  • [14] Single compartment drug delivery
    Cima, Michael J.
    Lee, Heejin
    Daniel, Karen
    Tanenbaum, Laura M.
    Mantzavinou, Aikaterini
    Spencer, Kevin C.
    Ong, Qunya
    Sy, Jay C.
    Santini, John, Jr.
    Schoellhammer, Carl M.
    Blankschtein, Daniel
    Langer, Robert S.
    [J]. JOURNAL OF CONTROLLED RELEASE, 2014, 190 : 157 - 171
  • [15] First-in-Human Studies for a Selective RET Tyrosine Kinase Inhibitor, GSK3179106, to Investigate the Safety, Tolerability, and Pharmacokinetics in Healthy Volunteers
    Cooper, Melisa
    O'Connor-Semmes, Robin
    Reedy, Beth Ann
    Hacquoil, Kimberley
    Gorycki, Peter
    Pannullo, Kristen
    Verticelli, Adeline
    Shakib, Sepehr
    [J]. CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT, 2019, 8 (02): : 234 - 245
  • [16] Deeks ED, 2021, DRUGS, V81, P1781, DOI 10.1007/s40265-021-01594-y
  • [17] Beyond the Rule of 5: Lessons Learned from AbbVie's Drugs and Compound Collection
    DeGoey, David A.
    Chen, Hui-Ju
    Cox, Philip B.
    Wendt, Michael D.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2018, 61 (07) : 2636 - 2651
  • [18] Dhaneshwar SS, 2011, CURR TOP MED CHEM, V11, P2318
  • [19] Oral Druggable Space beyond the Rule of 5: Insights from Drugs and Clinical Candidates
    Doak, Bradley Croy
    Over, Bjorn
    Giordanetto, Fabrizio
    Kihlberg, Jan
    [J]. CHEMISTRY & BIOLOGY, 2014, 21 (09): : 1115 - 1142
  • [20] Why Some Targets Benefit from beyond Rule of Five Drugs
    Egbert, Megan
    Whitty, Adrian
    Keseru, Gyorgy M.
    Vajda, Sandor
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2019, 62 (22) : 10005 - 10025
12345678