Término solicitado: ALONSO, DANIEL F./(22)
3 Registro/s encontrado/s en CAT+NORMA
| Tipo de Docum.: | artículo |
| Título: | Preclinical development of novel Rac1-GEF signaling inhibitors using a rational design approach in highly aggressive breast cancer cell lines |
| Autor: | Cardama, Georgina A.; Comin, Maria J.; Hornos, Leandro; Gonzalez, Nazareno; Defelipe, Lucas; Turjanski, Adrian G.; Alonso, Daniel F.; Gomez, Daniel E.; Lorenzano Menna, Pablo |
| Título Ser./Col.: | Anti-Cancer Agents in Medicinal Chemistry, 14(6) |
| Autor Inst. Ser./Col.: | Bentham Science Publishers |
| Idioma: | eng |
| Datos de Edición: | s.l. Bentham Science Publishers. 2014. |
| Pág./Vol.: | p. 840-851. |
| Descriptores: | Cáncer; Glándulas mamarias; Biología molecular; Células; Inhibidores; Tecnología médica; Lucha contra las enfermedades |
| Resumen: | Rho GTPases play a key role in the regulation of multiple essential cellular processes, including actin dynamics, gene transcription and cell cycle progression. Aberrant activation of Rac1, a member of Rho family of small GTPases, is associated with tumorigenesis, cancer progression, invasion and metastasis. Particularly, Rac1 is overexpressed and hyperactivated in highly aggressive breast cancer. Thus, Rac1 appears to be a promising and relevant target for the development of novel anticancer drugs. We identified the novel Rac1 inhibitor ZINC69391 through a docking-based virtual library screening targeting Rac1 activation by GEFs. This compound was able to block Rac1 interaction with its GEF Tiam1, prevented EGF-induced Rac1 activation and inhibited cell proliferation, cell migration and cell cycle progression in highly aggressive breast cancer cell lines. Moreover, ZINC69391 showed an in vivo antimetastatic effect in a syngeneic animal model. We further developed the novel analog 1A-116 by rational design and showed to be specific and more potent than the parental compound in vitro and interfered Rac1-P-Rex1 interaction. We also showed an enhanced in vivo potency of 1A-116 analog. These results show that we have developed novel Rac1 inhibitors that may be used as a novel anticancer therapy. |
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URL: |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104455/ |
| Tipo de Docum.: | artículo |
| Título: | Proapoptotic and antiinvasive activity of Rac1 small molecule inhibitors on malignant glioma cells |
| Autor: | Cardama, Georgina A.; Gonzalez, Nazareno; Ciarlantini, Matias; Gandolfi Donadío, Lucia; Comin, María Julieta; Alonso, Daniel F.; Lorenzano Menna, Pablo; Gomez, Daniel E. |
| Título Ser./Col.: | OncoTargets and Therapy, 7 |
| Idioma: | eng |
| Datos de Edición: | s.l. Dovepress. 2014. |
| Pág./Vol.: | p. 2021-2033. |
| Unidad técnica: | INTI-Química. |
| Descriptores: | Cáncer; Biología molecular; Células; Medicina |
| Resumen: | Malignant gliomas are characterized by an intrinsic ability to invade diffusely throughout the normal brain tissue. This feature contributes mainly to the failure of existing therapies. Deregulation of small GTPases signaling, in particular Rac1 activity, plays a key role in the invasive phenotype of gliomas. Here we report the effect of ZINC69391, a specific Rac1 inhibitor developed by our group, on human glioma cell lines LN229 and U-87 MG. ZINC69391 is able to interfere with the interaction of Rac1 with Dock180, a relevant Rac1 activator in glioma invasion, and to reduce Rac1-GTP levels. The kinase Pak1, a downstream effector of Dock180–Rac1 signaling, was also downregulated upon ZINC69391 treatment. ZINC69391 reduced cell proliferation, arrested cells in G1 phase, and triggered apoptosis in glioma cells. Importantly, ZINC69391 dramatically affected cell migration and invasion in vitro, interfering with actin cytoskeleton dynamics. We also evaluated the effect of analog 1A-116, a compound derived from ZINC69391 structure. 1A-116 showed an improved antiproliferative and antiinvasive activity on glioma cells. These findings encourage further preclinical testing in clinically relevant animal models. |
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URL: |
https://dx.doi.org/10.2147%2FOTT.S67998 |
| Tipo de Docum.: | documento de conferencia |
| Título: | Síntesis de nuevos compuestos con potenciales propiedades antitumorales |
| Autor: | Ciarlantini, M.; García, L.C.; Gandolfi Donadío, L.; Cardama, G.; Lorenzano Menna, P.; Gonzalez, N.; Alonso, Daniel F.; Gómez, D. E.; Defelipe, L.; Turjanski, A. G.; Blumberg, P. M.; Comin, M. J. |
| Reunión: | Instituto Nacional de Tecnología Industrial. INTI. Buenos Aires. AR, TecnoINTI edición 2015. Jornadas Abiertas de Desarrollo, Innovación y Transferencia Tecnológica, 12, Buenos Aires. AR, 2015 |
| Idioma: | spa |
| Datos de Edición: | Buenos Aires. AR. INTI. 2015. |
| Pág./Vol.: | 3p. |
| Unidad técnica: | INTI-Química. |
| Descriptores: | Optimización; Medicamentos; Cancer; Biología molecular |
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