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Future Med Chem. 2018 Apr 1;10(8):879-894. doi: 10.4155/fmc-2017-0178. Epub 2018 Mar 28.

Search of vasopressin analogs with antiproliferative activity on small-cell lung cancer: drug design based on two different approaches.

Author information

1
Laboratory of Molecular Oncology, Quilmes National University, Buenos Aires, 1876, Argentina.

Abstract

AIM:

Development of compounds with therapeutic application requires the interaction of different disciplines. Several tumors express vasopressin (AVP; arginine vasopressin) receptors with contrasting effects depending on receptor subtype. Desmopressin (dDAVP) is an AVP-selective analog with antiproliferative properties. In this work, an evolutionary approach and a rational strategy were applied in order to design novel AVP analogs.

RESULTS:

We designed two novel analogs; dDInotocin (dDINT, insect analog), and [V4Q5]dDAVP, and demonstrated the importance of the dDAVP conformational loop for its antiproliferative activity. [V4Q5] dDAVP showed major cytostatic effect on lung cancer cells than dDAVP and its cytostatic effect was abolished by V2R blockade.

CONCLUSION:

Combination of these strategies could provide the basis for future studies for the development of improved compounds with potential therapeutic applications.

KEYWORDS:

AVP; SAR studies; V2R agonists; antiproliferative; drug discovery; evolutionary approach

PMID:
29589487
DOI:
10.4155/fmc-2017-0178
[Indexed for MEDLINE]

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