RT Journal Article
T1 New inhibitors of angiogenesis with antitumor activity in vivo
A1 Marín Ramos, Nagore I.
A1 Alonso, Dulce
A1 Ortega Gutiérrez, Silvia
A1 Ortega Nogales, Francisco J.
A1 Balabasquer, Moisés
A1 Vázquez Villa, María Del Henar
A1 Andradas, Clara
A1 Blasco Benito, Sandra
A1 Pérez Gómez, Eduardo
A1 Canales Mayordomo, María Ángeles
A1 Jiménez Barbero, Jesus
A1 Marquina, Ana
A1 Moscoso del Prado, Jaime
A1 Sánchez García, María Cristina
A1 Martín-Fontecha Corrales, María Del Mar
A1 López Rodríguez, María Luz
AB Angiogenesis is a requirement for the sustained growth and proliferation of solid tumors, and the development of new compounds that induce a sustained inhibition of the proangiogenic signaling generated by tumor hypoxia still remains as an important unmet need. In this work, we describe a new antiangiogenic compound (22) that inhibits proangiogenic signaling under hypoxic conditions in breast cancer cells. Compound 22 blocks the MAPK pathway, impairs cellular migration under hypoxic conditions, and regulates a set of genes related to angiogenesis. These responses are mediated by HIF-1α, since the effects of compound 22 mostly disappear when its expression is knocked-down. Furthermore, administration of compound 22 in a xenograft model of breast cancer produced tumor growth reductions ranging from 46 to 55% in 38% of the treated animals without causing any toxic side effects. Importantly, in the responding tumors, a significant reduction in the number of blood vessels was observed, further supporting the mechanism of action of the compound. These findings provide a rationale for the development of new antiangiogenic compounds that could eventually lead to new drugs suitable for the treatment of some types of tumors either alone or in combination with other agents.
PB ACS Publications
SN 0022-2623
YR 2015
FD 2015-05-14
LK https://hdl.handle.net/20.500.14352/114166
UL https://hdl.handle.net/20.500.14352/114166
LA eng
NO Marín-Ramos, N. I., Alonso, D., Ortega-Gutiérrez, S., Ortega-Nogales, F. J., Balabasquer, M., Vázquez-Villa, H., Andradas, C., Blasco-Benito, S., Pérez-Gómez, E., Canales, A., Jiménez-Barbero, J., Marquina, A., Moscoso del Prado, J., Sánchez, C., Martín-Fontecha, M., López-Rodríguez, M. L. New Inhibitors of Angiogenesis with Antitumor Activity in Vivo. J. Med. Chem. 2015, 58 (9), 3757-3766
NO Ministerio de Economı́a y Competitividad
NO Instituto de Salud Carlos III
NO Comunidad de Madrid
NO Asociación Española Contra el Cáncer
NO Campus de Excelencia CEI Moncloa
DS Docta Complutense
RD 13 abr 2025