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

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

Future Med Chem. 2018 Mar 28;:

Authors: Pifano M, Garona J, Sobol NT, Albertó M, Alonso DF, Ripoll GV

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.

PMID: 29589487 [PubMed - as supplied by publisher]

https://ift.tt/2IfM7Zb