Beyond receptor expression levels: The relevance of target accessibility in ligand-directed pharmacodelivery systems

被引:37
|
作者
Ozawa, Michael G.
Zurita, Amado J.
Dias-Neto, Emmanuel
Nunes, Diana N.
Sidman, Richard L. [3 ,4 ]
Gelovani, Juri G. [2 ]
Arap, Wadih [1 ]
Pasqualini, Renata [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA
[3] Harvard Univ, Sch Med, Boston, MA 02115 USA
[4] Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/j.tcm.2008.03.001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
For development of a new ligand-directed pharmacology, it is critical to measure delivery of targeted drug ligands via molecular imaging or diagnostic readouts (termed theranostics). Combinatorial peptide libraries serve as unbiased functional screens that can identify specific peptides targeting cell-surface receptors accessible to the circulation. As candidate drug leads, such peptides provide motifs likely to modify ligand-receptor interactions and downstream signal transduction pathways. This strategy is synergistic with genomic and proteomic approaches and has yielded insights into the specialized nature of the target tissue microenvironment. However, for this vision to be realized, one must look, as recent literature suggests, beyond receptor levels and critically analyze ligand accessibility as a key determinant in pharmacodelivery systems.
引用
收藏
页码:126 / 133
页数:8
相关论文
共 50 条
  • [1] Ligand-directed trafficking of receptor stimulus
    Zdzisław Chilmonczyk
    Andrzej J. Bojarski
    Ingebrigt Sylte
    Pharmacological Reports, 2014, 66 : 1011 - 1021
  • [2] Ligand-directed trafficking of receptor stimulus
    Chilmonczyk, Zdzislaw
    Bojarski, Andrzej J.
    Sylte, Ingebrigt
    PHARMACOLOGICAL REPORTS, 2014, 66 (06) : 1011 - 1021
  • [3] Ligand-directed signalling within the opioid receptor family
    Pradhan, Amynah A.
    Smith, Monique L.
    Kieffer, Brigitte L.
    Evans, Christopher J.
    BRITISH JOURNAL OF PHARMACOLOGY, 2012, 167 (05) : 960 - 969
  • [4] Ligand-directed profiling: applications to target drug discovery in cancer
    Staquicini, Fernanda I.
    Pasqualini, Renata
    Arap, Wadih
    EXPERT OPINION ON DRUG DISCOVERY, 2009, 4 (01) : 51 - 59
  • [5] Kinase cascades and ligand-directed signaling at the kappa opioid receptor
    Michael R. Bruchas
    Charles Chavkin
    Psychopharmacology, 2010, 210 : 137 - 147
  • [6] Kinase cascades and ligand-directed signaling at the kappa opioid receptor
    Bruchas, Michael R.
    Chavkin, Charles
    PSYCHOPHARMACOLOGY, 2010, 210 (02) : 137 - 147
  • [7] Ligand-Directed Labeling of the Adenosine A1 Receptor in Living Cells
    Comeo, Eleonora
    Goulding, Joelle
    Lin, Chia-Yang
    Groenen, Marleen
    Woolard, Jeanette
    Kindon, Nicholas D.
    Harwood, Clare R.
    Platt, Simon
    Briddon, Stephen J.
    Kilpatrick, Laura E.
    Scammells, Peter J.
    Hill, Stephen J.
    Kellam, Barrie
    JOURNAL OF MEDICINAL CHEMISTRY, 2024, 67 (14) : 12099 - 12117
  • [8] Ligand-Directed Divergent Synthesis of Carbo- and Heterocyclic Ring Systems
    Lee, Yen-Chun
    Kumar, Kamal
    Waldmann, Herbert
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2018, 57 (19) : 5212 - 5226
  • [9] Ligand-Directed Functional Selectivity at the Mu Opioid Receptor Revealed by Label-Free Integrative Pharmacology On-Target
    Morse, Megan
    Tran, Elizabeth
    Sun, Haiyan
    Levenson, Robert
    Fang, Ye
    PLOS ONE, 2011, 6 (10):
  • [10] Kinetic Machine Learning Unravels Ligand-Directed Conformational Change of μ Opioid Receptor
    Feinberg, Evan N.
    Pande, Vijay S.
    Farimani, Amir Barati
    Hernandez, Carlos X.
    BIOPHYSICAL JOURNAL, 2018, 114 (03) : 56A - 56A