Preclinical development of novel Rac1-GEF signaling inhibitors using a rational design approach in highly aggressive breast cancer cell lines

Mostrar otras versiones (1)

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 me...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autor principal: Cardama, G.A
Otros Autores: Comin, M.J, Hornos, L., Gonzalez, N., Defelipe, L., Turjanski, A.G, Alonso, D.F, Gomez, D.E, Menna, P.L
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: Bentham Science Publishers B.V. 2014
Materias:
nsc23766; zinc69391
Acceso en línea:Registro en Scopus
DOI
Handle
Registro en la Biblioteca Digital
Aporte de:Registro referencial: Solicitar el recurso aquí
Biblioteca Central Dr. Luis F. Leloir (FCEN) de Universidad de Buenos Aires
LEADER 22218caa a22024137a 4500
001 PAPER-23917
003 AR-BaUEN
005 20230518205541.0
008 190411s2014 xx ||||fo|||| 00| 0 eng|d
024 7 |2 scopus  |a 2-s2.0-84904128480 
024 7 |2 cas  |a 4 amino 6 [2 [[4 (diethylamino) 1 methylbutyl]amino] 6 methyl 4 pyrimidinyl] 2 methylquinoline, 733767-34-5; epidermal growth factor, 62229-50-9; Antineoplastic Agents; Guanidines; Guanine Nucleotide Exchange Factors; Pyrimidines; rac1 GTP-Binding Protein; RAC1 protein, human; ZINC69391 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
100 1 |a Cardama, G.A. 
245 1 0 |a Preclinical development of novel Rac1-GEF signaling inhibitors using a rational design approach in highly aggressive breast cancer cell lines 
260 |b Bentham Science Publishers B.V.  |c 2014 
270 1 0 |m Gomez, D. E.; Laboratorio de Oncología Molecular, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal B1876BXD Buenos Aires, Argentina; email: degomez@unq.edu.ar 
506 |2 openaire  |e Política editorial 
504 |a Etienne-Manneville, S., Hall, A., Rho GTPases in cell biology (2002) Nature, 420 (6916), pp. 629-635 
504 |a Bishop, A.L., Hall, A., Rho GTPases and their effector proteins (2000) Biochem. J, 348 (Pt 2), pp. 241-255 
504 |a Bosco, E.E., Mulloy, J.C., Zheng, Y., Rac1 GTPase: A Rac of all trades (2009) Cell Mol. Life Sci, 66 (3), pp. 370-374 
504 |a Ellenbroek, S.I., Collard, J.G., Rho GTPases: Functions and association with cancer (2007) Clin. Exp. Metastasis, 24 (8), pp. 657-672 
504 |a Fritz, G., Just, I., Kaina, B., Rho GTPases are over-expressed in human tumors (1999) Int. J. Cancer, 81 (5), pp. 682-687 
504 |a Fritz, G., Brachetti, C., Bahlmann, F., Schmidt, M., Kaina, B., Rho GTPases in human breast tumours: Expression and mutation analyses and correlation with clinical parameters (2002) Br. J. Cancer, 87 (6), pp. 635-644 
504 |a Kamai, T., Yamanishi, T., Shirataki, H., Takagi, K., Asami, H., Ito, Y., Yoshida, K., Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer (2004) Clin. Cancer Res, 10, pp. 4799-4805 
504 |a Buongiorno, P., Bapat, B., Rho GTPases and cancer (2005) Prog. Mol. Subcell. Biol, 40, pp. 29-53 
504 |a Schnelzer, A., Prechtel, D., Knaus, U., Dehne, K., Gerhard, M., Graeff, H., Harbeck, N., Lengyel, E., Rac1 in human breast cancer: Overexpression, mutation analysis, and characterization of a new isoform, Rac1b (2000) Oncogene, 19 (26), pp. 3013-3020 
504 |a Khosravi-Far, R., Solski, P.A., Clark, G.J., Kinch, M.S., Der, C.J., Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation (1995) Mol. Cell. Biol, 15, pp. 6443-6453 
504 |a Fritz, G., Kaina, B., Rho GTPases: Promising cellular targets for novel anticancer drugs (2006) Curr. Cancer Drug Targets, 6 (1), p. 1 
504 |a Vigil, D., Cherfils, J., Rossman, K.L., Der, C.J., Ras superfamily GEFs and GAPs: Validated and tractable targets for cancer therapy (2010) Nat. Rev. Cancer, 10 (12), pp. 842-857 
504 |a Krauthammer, M., Kong, Y., Ha, B.H., Evans, P., Bacchiocchi, A., McCusker, J.P., Cheng, E., Halaban, R., Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma (2012) Nat. Genet, 44 (9), pp. 1006-1014 
504 |a Hodis, E., Watson, I.R., Kryukov, G.V., Arold, S.T., Imielinski, M., Theurillat, J.P., Nickerson, E., Chin, L., A landscape of driver mutations in melanoma (2012) Cell, 150 (2), pp. 251-263 
504 |a Rossman, K.L., Der, C.J., Sondek, J., GEF means go: Turning on RHO GTPases with guanine nucleotide-exchange factors (2005) Nat. Rev. Mol. Cell Biol, 6 (2), pp. 167-180 
504 |a Fields, A.P., Justilien, V., The guanine nucleotide exchange factor (GEF) Ect2 is an oncogene in human cancer (2010) Adv. Enzyme Regul, 50 (1), pp. 190-200 
504 |a van Leeuwen, F.N., Van der Kammen, R.A., Habets, G.G., Collard, J.G., Oncogenic activity of Tiam1 and Rac1 in NIH3T3 cells (1995) Oncogene, 11 (11), pp. 2215-2221 
504 |a Gao, Y., Xing, J., Streuli, M., Leto, T.L., Zheng, Y., Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors (2001) J. Biol. Chem, 276 (50), pp. 47530-47541 
504 |a Karnoub, A.E., Worthylake, D.K., Rossman, K.L., Pruitt, W.M., Campbell, S.L., Sondek, J., Der, C.J., Molecular basis for Rac1 recognition by guanine nucleotide exchange factors (2001) Nat. Struct. Biol, 8 (12), pp. 1037-1041 
504 |a Wu, X., Ramachandran, S., Lin, M.C., Cerione, R.A., Erickson, J.W., A minimal Rac activation domain in the unconventional guanine nucleotide exchange factor Dock180 (2011) Biochemistry, 50 (6), pp. 1070-1080 
504 |a Shoichet, B.K., Virtual screening of chemical libraries (2004) Nature, 432 (7019), pp. 862-865 
504 |a Cosconati, S., Forli, S., Perryman, A.L., Harris, R., Goodsell, D.S., Olson, A.J., Virtual screening with autodock: Theory and practice (2010) Expert Opin. Drug Discov, 5 (6), pp. 597-607 
504 |a Irwin, J.J., Shoichet, B.K., ZINC--a free database of commercially available compounds for virtual screening (2005) J. Chem. Inf. Model, 45 (1), pp. 177-182 
504 |a Irwin, J.J., Sterling, T., Mysinger, M.M., Bolstad, E.S., Coleman, R.G., ZINC: A free tool to discover chemistry for biology (2012) J. Chem. Inf. Model, 52 (7), pp. 1757-1768 
504 |a Zsoldos, Z., Reid, D., Simon, A., Sadjad, S.B., Johnson, A.P., eHiTS: A new fast, exhaustive flexible ligand docking system (2007) J. Mol. Graph Model, 26 (1), pp. 198-212 
504 |a Morris, G.M., Huey, R., Olson, A.J., Using AutoDock for ligandreceptor docking (2008) Curr. Protoc. Bioinformatics, 8, p. 14. , Chapter 8:Unit 
504 |a Alonso, D.F., Farías, E.F., Urtreger, A., Ladeda, V., Vidal, M.C., de Kier, B., Joffé, E., Characterization of F3II, a sarcomatoid mammary carcinoma cell line originated from a clonal subpopulation of a mouse adenocarcinoma (1996) J. Surg. Oncol, 62 (4), pp. 288-297 
504 |a Best, A., Ahmed, S., Kozma, R., Lim, L., The Ras-related GTPase Rac1 binds tubulin (1996) J. Biol. Chem, 271 (7), pp. 3756-3762 
504 |a Habets, G.G., Scholtes, E.H., Zuydgeest, D., van der Kammen, R.A., Stam, J.C., Berns, A., Collard, J.G., Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins (1994) Cell, 77 (4), pp. 537-549 
504 |a Stam, J.C., Sander, E.E., Michiels, F., van Leeuwen, F.N., Kain, H.E., Van der Kammen, R.A., Collard, J.G., Targeting of Tiam1 to the plasma membrane requires the cooperative function of the Nterminal pleckstrin homology domain and an adjacent protein interaction domain (1997) J. Biol. Chem, 272 (45), pp. 28447-28454 
504 |a Sosa, M.S., Lopez-Haber, C., Yang, C., Wang, H., Lemmon, M.A., Busillo, J.M., Luo, J., Kazanietz, M.G., Identification of the Rac-GEF P-Rex1 as an essential mediator of ErbB signaling in breast cancer (2011) Mol. Cell, 40, p. 877 
504 |a Segatori, V.I., Otero, L.L., Fernandez, L.E., Gomez, D.E., Alonso, D.F., Gabri, M.R., (2012) Antitumor Protection By NGcGM3/VSSP Vaccine Against Transfected B16 Mouse Melanoma Cells Overexpressing N-glycolylated Gangliosides, 26 (4), pp. 609-617. , In vivo 
504 |a Guidance Document on Using In Vitro Data to Estimate In Vivo Starting Doses for Acute Toxicity (2001) NIH Publication No, pp. 01-4500. , National Institute of Health (NIH) 
504 |a Fanger, G.R., Johnson, N.L., Johnson, G.L., MEK kinases are regulated by EGF and selectively interact with Rac/Cdc42 (1997) EMBO J, 16 (16), pp. 4961-4972 
504 |a Itoh, R.E., Kiyokawa, E., Aoki, K., Nishioka, T., Akiyama, T., Matsuda, M., Phosphorylation and activation of the Rac1 and Cdc42 GEF Asef in A431 cells stimulated by EGF (2008) J. Cell Sci, 121 (Pt 16), pp. 2635-2642 
504 |a Menna, P.L., Skilton, G., Leskow, F.C., Alonso, D.F., Gomez, D.E., Kazanietz, M.G., Inhibition of aggressiveness of metastatic mouse mammary carcinoma cells by the beta2-chimaerin GAP domain (2003) Cancer Res, 63 (9), pp. 2284-2291 
504 |a Snyder, J.T., Worthylake, D.K., Rossman, K.L., Betts, L., Pruitt, W.M., Siderovski, D.P., Der, C.J., Sondek, J., Structural basis for the selective activation of Rho GTPases by Dbl exchange factors (2002) Nat. Struct. Biol, 9 (6), pp. 468-475 
504 |a Yang, C., Liu, Y., Leskow, F.C., Weaver, V.M., Kazanietz, M.G., Rac-GAP-dependent inhibition of breast cancer cell proliferation by {beta}2-chimerin (2005) J. Biol. Chem, 280 (26), pp. 24363-24370 
504 |a Montalvo-Ortiz, B.L., Castillo-Pichardo, L., Hernández, E., Humphries-Bickley, T., De la Mota-Peynado, A., Cubano, L.A., Vlaar, C.P., Dharmawardhane, S., Characterization of EHop-016, novel small molecule inhibitor of Rac GTPase (2012) J. Biol. Chem, 287 (16), pp. 13228-13238 
504 |a Yoshida, T., Zhang, Y., Rivera, R.L.A., Chen, J., Khan, T., Moon, S.Y., Zhang, B., Blockade of Rac1 activity induces G1 cell cycle arrest or apoptosis in breast cancer cells through downregulation of cyclin D1, survivin, and X-linked inhibitor of apoptosis protein (2010) Mol. Cancer Ther, 9 (6), pp. 1657-1668 
504 |a Hall, A., Rho GTPases and the actin cytoskeleton (1998) Science, 279 (5350), pp. 509-514 
504 |a Ridley, Rho, A.J., GTPases and cell migration (2001) J. Cell Sci, 114 (Pt 15), pp. 2713-2722 
504 |a Li, S., Wang, Q., Wang, Y., Chen, X., Wang, Z., PLC-gamma1 and Rac1 coregulate EGF-induced cytoskeleton remodeling and cell migration (2009) Mol. Endocrinol, 23 (6), pp. 901-913 
504 |a Tetko, I.V., Gasteiger, J., Todeschini, R., Mauri, A., Livingstone, D., Ertl, P., Palyulin, V.A., Prokopenko, V.V., Virtual computational chemistry laboratory -design and description (2005) J. Comput. Aid. Mol. Des, 19 (6), pp. 453-463 
504 |a Montero, J.C., Seoane, S., Ocana, A., Pandiella, A., P-Rex1 participates in Neuregulin-ErbB signaltransduction and its expression correlates with patient outcome in breast cancer (2011) Oncogene, 30, pp. 1059-1071 
504 |a Han, S.S.R., Cho, C.K., Lee, Y.W., Yoo, H.S., Antimetastatic and immunomodulating effect of water extracts from various mushrooms (2009) J. Acupunct. Meridian Stud, 2 (3), pp. 218-227 
504 |a Ma, J., Xue, Y., Liu, W., Yue, C., Bi, F., Xu, J., Zhang, J., Chen, Y., Role of activated rac1/cdc42 in mediating endothelial cell proliferation and tumor angiogenesis in breast cancer (2013) PLoS One, 8 (6), pp. e66275 
504 |a Katz, E., Sims, A.H., Sproul, D., Caldwell, H., Dixon, M.J., Meehan, R.R., Harrison, D.J., Targeting of Rac GTPases blocks the spread of intact human breast cancer (2012) Oncotarget, 3 (6), pp. 608-619 
504 |a Jordan, P., Brazåo, R., Boavida, M.G., Gespach, C., Chastre, E., Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors (1999) Oncogene, 18 (48), pp. 6835-6839 
504 |a Radisky, D.C., Levy, D.D., Littlepage, L.E., Liu, H., Nelson, C.M., Fata, J.E., Leake, D., Bissell, M.J., Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability (2005) Nature, 436 (7047), pp. 123-127 
504 |a Singh, A., Karnoub, A.E., Palmby, T.R., Lengyel, E., Sondek, J., Der, C.J., Rac1b, a tumor associated, constitutively active Rac1 splice variant, promotes cellular transformation (2004) Oncogene, 23 (58), pp. 9369-9380 
504 |a Herter-Sprie, G.S., Greulich, H., Wong, K.K., Activating mutations in ERBB2 and their impact on diagnostics and treatment (2013) Front. Oncol, 3, p. 86 
504 |a Saini, K.S., Loi, S., de Azambuja, E., Metzger-Filho, O., Saini, M.L., Ignatiadis, M., Dancey, J.E., Piccart-Gebhart, M.J., Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer (2013) Cancer Treat. Rev, 39 (8), pp. 935-946 
504 |a Jhaveri, K., Modi, S., HSP90 inhibitors for cancer therapy and overcoming drug resistance (2012) Adv. Pharmacol, 65, pp. 471-517 
504 |a Aznar, S., Fernández-Valerón, P., Espina, C., Lacal, J.C., Rho GTPases: Potential candidates for anticancer therapy (2004) Cancer Lett, 206 (2), pp. 181-191 
504 |a Wang, C.Y., Liu, P.Y., Liao, J.K., Pleiotropic effects of statin therapy: Molecular mechanisms and clinical results (2008) Trends Mol. Med, 14 (1), pp. 37-44 
504 |a Tiede, I., Fritz, G., Strand, S., Poppe, D., Dvorsky, R., Strand, D., Lehr, H.A., Neurath, M.F., CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes (2003) J. Clin. Invest, 111 (8), pp. 1133-1145 
504 |a Poppe, D., Tiede, I., Fritz, G., Becker, C., Bartsch, B., Wirtz, S., Strand, D., Neurath, M.F., Azathioprine suppresses ezrin-radixin-moesin-dependent T cell-APC conjugation through inhibition of Vav guanosine exchange activity on Rac proteins (2006) J. Immunol, 176 (1), pp. 640-651 
504 |a Menna, P.L., Parera, R.L., Cardama, G.A., Alonso, D.F., Gomez, D.E., Farina, H.G., Enhanced cytostatic activity of statins in mouse mammary carcinoma cells overexpressing β2-chimaerin (2009) Mol. Med. Report, 2 (1), pp. 97-102 
504 |a Gao, Y., Dickerson, J.B., Guo, F., Zheng, J., Zheng, Y., Rational design and characterization of a Rac GTPase-specific small molecule inhibitor (2004) Proc. Natl. Acad. Sci. USA, 101 (20), pp. 7618-7623 
504 |a Ferri, N., Corsini, A., Bottino, P., Clerici, F., Contini, A., Virtual screening approach for the identification of new Rac1 inhibitors (2009) J. Med. Chem, 52 (14), pp. 4087-4090 
504 |a Hernández, E., De La Mota-Peynado, A., Dharmawardhane, S., Vlaar, C.P., Novel inhibitors of Rac1 in metastatic breast cancer (2010) P R Health Sci. J, 29 (4), pp. 348-356 
504 |a Vives, V., Laurin, M., Cres, G., Larrousse, P., Morichaud, Z., Noel, D., Côté, J.F., Blangy, A., The Rac1 exchange factor Dock5 is essential for bone resorption by osteoclasts (2011) J. Bone Miner. Res, 26 (5), pp. 1099-1110 
504 |a Bouquier, N., Vignal, E., Charrasse, S., Weill, M., Schmidt, S., Léonetti, J.P., Blangy, A., Fort, P., A cell active chemical GEF inhibitor selectively targets the Trio/RhoG/Rac1 signaling pathway (2009) Chem. Biol, 16 (6), pp. 657-666 
504 |a Blangy, A., Bouquier, N., Gauthier-Rouvière, C., Schmidt, S., Debant, A., Leonetti, J.P., Fort, P., Identification of TRIO-GEFD1 chemical inhibitors using the yeast exchange assay (2006) Biol. Cell, 98 (9), pp. 511-522 
504 |a Shutes, A., Onesto, C., Picard, V., Leblond, B., Schweighoffer, F., Der, C.J., Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases (2007) J. Biol. Chem, 282 (49), pp. 35666-35678 
504 |a Bosco, E.E., Kumar, S., Marchioni, F., Biesiada, J., Kordos, M., Szczur, K., Meller, J., Zheng, Y., Rational design of small molecule inhibitors targeting the Rac GTPase-p67(phox) signaling axis in inflammation (2012) Chem. Biol, 19 (2), pp. 228-242 
504 |a Murray, B.W., Guo, C., Piraino, J., Westwick, J.K., Zhang, C., Lamerdin, J., Dagostino, E., Smeal, T., Smallmolecule p21-activated kinase inhibitor PF-3758309 is a potent inhibitor of oncogenic signaling and tumor growth (2010) Proc. Natl. Acad. Sci. USA, 107 (20), pp. 9446-9451 
504 |a Pearson, H.B., Pouliot, N., Modeling Metastasis In Vivo Metastatic Cancer: Integrated Organ System and Biological Approach, p. 2012. , Rahul Jandial and Kent Hunter, Ed.; Landes Bioscience 
504 |a Wertheimer, E., Gutierrez-Uzquiza, A., Rosemblit, C., Lopez-Haber, C., Sosa, M.S., Kazanietz, M.G., Rac signaling in breast cancer: A tale of GEFs and GAPs (2012) Cell Signal, 24 (2), pp. 353-362 
520 3 |a 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. © 2014 Bentham Science Publishers.  |l eng 
593 |a Laboratorio de Oncología Molecular, Universidad Nacional de Quilmes, Bernal, B1876BXD, Buenos Aires, Argentina 
593 |a Centro de Investigación y Desarrollo en Química, Instituto Nacional de Tecnología Industrial (INTI) and CONICET, San Martín, B1650WAB, Argentina 
593 |a Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE-CONICET, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires C1428EHA, Argentina 
593 |a Departamento de Química Biológica, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires C1428EHA, Argentina 
690 1 0 |a BREAST CANCER 
690 1 0 |a DOCKING 
690 1 0 |a RAC1 INHIBITOR 
690 1 0 |a RATIONAL DESIGN 
690 1 0 |a VIRTUAL SCREENING 
690 1 0 |a 1A 116 
690 1 0 |a 4 AMINO 6 [2 [[4 (DIETHYLAMINO) 1 METHYLBUTYL] AMINO] 6 METHYL 4 PYRIMIDINYL] 2 METHYLQUINOLINE 
690 1 0 |a 4 AMINO 6 [2 [[4 (DIETHYLAMINO) 1 METHYLBUTYL]AMINO] 6 METHYL 4 PYRIMIDINYL] 2 METHYLQUINOLINE 
690 1 0 |a ACTIN 
690 1 0 |a ANTINEOPLASTIC AGENT 
690 1 0 |a EPIDERMAL GROWTH FACTOR 
690 1 0 |a GUANINE NUCLEOTIDE EXCHANGE FACTOR 
690 1 0 |a PEPTIDES AND PROTEINS 
690 1 0 |a RAC1 PROTEIN 
690 1 0 |a TIAM1 PROTEIN 
690 1 0 |a UNCLASSIFIED DRUG 
690 1 0 |a ZINC69391 
690 1 0 |a ANTINEOPLASTIC AGENT 
690 1 0 |a GUANIDINE DERIVATIVE 
690 1 0 |a GUANINE NUCLEOTIDE EXCHANGE FACTOR 
690 1 0 |a PYRIMIDINE DERIVATIVE 
690 1 0 |a RAC1 PROTEIN 
690 1 0 |a RAC1 PROTEIN, HUMAN 
690 1 0 |a ZINC69391 
690 1 0 |a ANIMAL CELL 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL MODEL 
690 1 0 |a ANIMAL TISSUE 
690 1 0 |a ANTIPROLIFERATIVE ACTIVITY 
690 1 0 |a ARTICLE 
690 1 0 |a BIOASSAY 
690 1 0 |a BREAST CANCER 
690 1 0 |a CELL CYCLE ASSAY 
690 1 0 |a CELL CYCLE PROGRESSION 
690 1 0 |a CELL MIGRATION 
690 1 0 |a CELL MIGRATION ASSAY 
690 1 0 |a CELL PROLIFERATION 
690 1 0 |a CELL PROLIFERATION ASSAY 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a DRUG DESIGN 
690 1 0 |a DRUG IDENTIFICATION 
690 1 0 |a FEMALE 
690 1 0 |a FLOW CYTOMETRY 
690 1 0 |a HUMAN 
690 1 0 |a HUMAN CELL 
690 1 0 |a IC 50 
690 1 0 |a LUNG METASTASIS 
690 1 0 |a METASTASIS INHIBITION 
690 1 0 |a MOLECULAR DOCKING 
690 1 0 |a MOUSE 
690 1 0 |a MTT ASSAY 
690 1 0 |a NONHUMAN 
690 1 0 |a PRECIPITATION 
690 1 0 |a PROTEIN INTERACTION 
690 1 0 |a PULL DOWN ASSAY 
690 1 0 |a SCREENING 
690 1 0 |a SIGNAL TRANSDUCTION 
690 1 0 |a ANIMAL 
690 1 0 |a ANTAGONISTS AND INHIBITORS 
690 1 0 |a BREAST NEOPLASMS 
690 1 0 |a CELL CYCLE 
690 1 0 |a CHEMICAL STRUCTURE 
690 1 0 |a CHEMISTRY 
690 1 0 |a DOSE RESPONSE 
690 1 0 |a DRUG EFFECTS 
690 1 0 |a DRUG SCREENING 
690 1 0 |a HEK293 CELL LINE 
690 1 0 |a MCF 7 CELL LINE 
690 1 0 |a METABOLISM 
690 1 0 |a PATHOLOGY 
690 1 0 |a STRUCTURE ACTIVITY RELATION 
690 1 0 |a SYNTHESIS 
690 1 0 |a TUMOR CELL LINE 
690 1 0 |a ANIMALS 
690 1 0 |a ANTINEOPLASTIC AGENTS 
690 1 0 |a BREAST NEOPLASMS 
690 1 0 |a CELL CYCLE 
690 1 0 |a CELL LINE, TUMOR 
690 1 0 |a CELL PROLIFERATION 
690 1 0 |a DOSE-RESPONSE RELATIONSHIP, DRUG 
690 1 0 |a DRUG DESIGN 
690 1 0 |a DRUG SCREENING ASSAYS, ANTITUMOR 
690 1 0 |a FEMALE 
690 1 0 |a GUANIDINES 
690 1 0 |a GUANINE NUCLEOTIDE EXCHANGE FACTORS 
690 1 0 |a HEK293 CELLS 
690 1 0 |a HUMANS 
690 1 0 |a MCF-7 CELLS 
690 1 0 |a MICE 
690 1 0 |a MODELS, MOLECULAR 
690 1 0 |a MOLECULAR STRUCTURE 
690 1 0 |a PYRIMIDINES 
690 1 0 |a RAC1 GTP-BINDING PROTEIN 
690 1 0 |a SIGNAL TRANSDUCTION 
690 1 0 |a STRUCTURE-ACTIVITY RELATIONSHIP 
653 0 0 |a nsc23766; zinc69391 
700 1 |a Comin, M.J. 
700 1 |a Hornos, L. 
700 1 |a Gonzalez, N. 
700 1 |a Defelipe, L. 
700 1 |a Turjanski, A.G. 
700 1 |a Alonso, D.F. 
700 1 |a Gomez, D.E. 
700 1 |a Menna, P.L. 
773 0 |d Bentham Science Publishers B.V., 2014  |g v. 14  |h pp. 840-851  |k n. 6  |p Anti-Cancer Agents Med. Chem.  |x 18715206  |t Anti-Cancer Agents in Medicinal Chemistry 
856 4 1 |u https://www.scopus.com/inward/record.uri?eid=2-s2.0-84904128480&doi=10.2174%2f18715206113136660334&partnerID=40&md5=36da3a8130c40c44c0930b6ff27e724a  |y Registro en Scopus 
856 4 0 |u https://doi.org/10.2174/18715206113136660334  |y DOI 
856 4 0 |u https://hdl.handle.net/20.500.12110/paper_18715206_v14_n6_p840_Cardama  |y Handle 
856 4 0 |u https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_18715206_v14_n6_p840_Cardama  |y Registro en la Biblioteca Digital 
961 |a paper_18715206_v14_n6_p840_Cardama  |b paper  |c PE 
962 |a info:eu-repo/semantics/article  |a info:ar-repo/semantics/artículo  |b info:eu-repo/semantics/publishedVersion 
999 |c 84870 

Ejemplares similares