Early evaluation of opportunities in oral delivery of PROTACs to overcome their molecular challenges

被引：7
|
作者：
Yang, Wenzhan [1 ]
Saboo, Sugandha [1 ]
Zhou, Liping [1 ]
Askin, Sean [2 ]
Bak, Annette [1 ]
机构：
[1] AstraZeneca, Adv Drug Delivery, Pharmaceut Sci, R&D, Boston, MA 02451 USA
[2] AstraZeneca, Adv Drug Delivery, Pharmaceut Sci, R&D, Cambridge, England
来源：
DRUG DISCOVERY TODAY | 2024年 / 29卷 / 02期
关键词：
drug delivery; PROTAC; drug discovery; lipid-based formulations (LBF); amorphous solid dispersions (ASDs); LIPID-BASED FORMULATIONS; WATER-SOLUBLE DRUGS; PRECIPITATION INHIBITORS; CYCLOSPORINE-A; SYSTEMS; ABSORPTION; BIOAVAILABILITY; CLASSIFICATION; SOLUBILITY; PERMEABILITY;
D O I：
10.1016/j.drudis.2023.103865
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
PROteolysis TArgeting Chimeras (PROTACs) offer new opportunities in modern medicine by targeting proteins that are intractable to classic inhibitors. Heterobifunctional in nature, PROTACs are small molecules that offer a unique mechanism of protein degradation by hijacking the ubiquitin-mediated protein degradation pathway, known as the ubiquitin-proteasome system. Herein, we present an analysis on the structural characteristics of this novel chemical modality. Furthermore, we review and discuss the formulation opportunities to overcome the oral delivery challenges of PROTACs in drug discovery.
引用
收藏
页数：12
相关论文
共 50 条
  • [1] Solubility Enhanced Formulation Approaches to Overcome Oral Delivery Obstacles of PROTACs
    Poestges, Florian
    Kayser, Kevin
    Appelhaus, Jan
    Monschke, Marius
    Gutschow, Michael
    Steinebach, Christian
    Wagner, Karl G. G.
    PHARMACEUTICS, 2023, 15 (01)
  • [2] Oral delivery of anticancer drugs: Challenges and opportunities
    Thanki, Kaushik
    Gangwal, Rahul P.
    Sangamwar, Abhay T.
    Jain, Sanyog
    JOURNAL OF CONTROLLED RELEASE, 2013, 170 (01) : 15 - 40
  • [3] Challenges and Opportunities in the Oral Delivery of Recombinant Biologics
    Masloh, Solene
    Culot, Maxime
    Gosselet, Fabien
    Chevrel, Anne
    Scapozza, Leonardo
    Zeisser Labouebe, Magali
    PHARMACEUTICS, 2023, 15 (05)
  • [4] Copolymeric Micelles Overcome the Oral Delivery Challenges of Amphotericin B
    Nimtrakul, Pataranapa
    Williams, Desmond B.
    Tiyaboonchai, Waree
    Prestidge, Clive A.
    PHARMACEUTICALS, 2020, 13 (06) : 1 - 14
  • [5] Molecular simulations in drug delivery: Opportunities and challenges
    Katiyar, Ratna S.
    Jha, Prateek K.
    WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE, 2018, 8 (04)
  • [6] Advances in Oral Drug Delivery Systems: Challenges and Opportunities
    Lou, Jie
    Duan, Hongli
    Qin, Qin
    Teng, Zhipeng
    Gan, Fengxu
    Zhou, Xiaofang
    Zhou, Xing
    PHARMACEUTICS, 2023, 15 (02)
  • [7] Challenges in oral drug delivery of antiretrovirals and the innovative strategies to overcome them
    Sosnik, Alejandro
    Augustine, Robin
    ADVANCED DRUG DELIVERY REVIEWS, 2016, 103 : 105 - 120
  • [8] Inhibitors and PROTACs of CDK2: challenges and opportunities
    Zeng, Yangjie
    Ren, Xiaodong
    Jin, Pengyao
    Fan, Zhida
    Liu, Mengguang
    Zhang, Yali
    Li, Linzhao
    Zhuo, Ming
    Wang, Jubo
    Li, Zhiyu
    Wu, Min
    EXPERT OPINION ON DRUG DISCOVERY, 2024, 19 (09) : 1125 - 1148
  • [9] Local drug delivery for oral mucosal diseases: challenges and opportunities
    Sankar, V.
    Hearnden, V.
    Hull, K.
    Juras, D. Vidovic
    Greenberg, M. S.
    Kerr, A. R.
    Lockhart, P. B.
    Patton, L. L.
    Porter, S.
    Thornhill, M.
    ORAL DISEASES, 2011, 17 : 73 - 84
  • [10] Oral delivery of nucleic acid therapeutics: Challenges, strategies, and opportunities
    Jiang, Xiaohe
    Wang, Ning
    Liu, Chang
    Zhuo, Yan
    Liang, Li
    Gan, Yong
    Yu, Miaorong
    DRUG DISCOVERY TODAY, 2023, 28 (04)
12345