PTX3:n synteettinen derivaatta NSCI2 , "pan- FGF2 trap"

https://pubs.acs.org/doi/10.1021/acs.jmedchem.5b02021

J Med Chem. 2016 May 26;59(10):4651-63. doi: 10.1021/acs.jmedchem.5b02021. Epub 2016 May 3.

Synthesis, Structural Elucidation, and Biological Evaluation of NSC12, an Orally Available Fibroblast Growth Factor (FGF) Ligand Trap for the Treatment of FGF-Dependent Lung Tumors.

Castelli R¹, Giacomini A², Anselmi M¹, Bozza N¹, Vacondio F¹, Rivara S¹, Matarazzo S², Presta M², Mor M¹, Ronca R².

Abstract

NSC12 is an orally available pan-FGF trap able to inhibit FGF2/FGFR interaction and endowed with promising antitumor activity. It was identified by virtual screening from a NCI small molecule library, but no data were available about its synthesis, stereochemistry, and physicochemical properties. We report here a synthetic route that allowed us to characterize and unambiguously identify the structure of the active compound by a combination of NMR spectroscopy and in silico conformational analysis. The synthetic protocol allowed us to sustain experiments aimed at assessing its therapeutic potential for the treatment of FGF-dependent lung cancers. A crucial step in the synthesis generated a couple of diastereoisomers, with only one able to act as a FGF trap molecule and to inhibit FGF-dependent receptor activation, cell proliferation, and tumor growth when tested in vitro and in vivo on murine and human lung cancer cells.

PMID:

27138345

DOI:

10.1021/acs.jmedchem.5b02021

[Indexed for MEDLINE] 

 

(Olen pohtimassa tämän  pentraxiini-proteiiniperheen ja  sen derivaatan NSCI  merkitystä, joten   artikkeli on muistissa tässä aminohappoblogissa toistaiseksi. 16.11. 2018)

Lähdin seulomaan AMP peptidejä , ja  pentraxiini PTX3 mainittiin joukossa)