Small series of acylguanidine and acylthiourea derivatives were synthesized in gram-scale and assayed for their ability to modulate the Hh signalling pathway. In vitro studies showed a low micromolar inhibitory activity toward tumor cell lines, while the oral administration revealed an excellent ADME profile in vivo. Compound 5 emerged as the most active and safe inhibitor of colon cancer cells both in vitro and in a xenograft mouse model. Based on these data, 5 could be prioritized to further development with the perspective of clinical studies.
|Titolo:||Hedgehog pathway inhibitors of the acylthiourea and acylguanidine class show antitumor activity on colon cancer in vitro and in vivo|
CINI, ELENA [Methodology]
PETRICCI, ELENA [Conceptualization] (Corresponding)
MANETTI, FABRIZIO [Conceptualization]
GIANNINI, GIUSEPPE [Supervision] (Corresponding)
|Citazione:||Vesci, L., Milazzo, F.M., Stasi, M.A., Pace, S., Manera, F., Tallarico, C., et al. (2018). Hedgehog pathway inhibitors of the acylthiourea and acylguanidine class show antitumor activity on colon cancer in vitro and in vivo. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 157, 368-379.|
|Appare nelle tipologie:||1.1 Articolo in rivista|