Research Topics
Species | L T VassilevSummaryAffiliation: F. Hoffmann-La Roche Ltd Publications
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Detail Information
Publications
Identification of phenyl-pyridine-2-carboxylic acid derivatives as novel cell cycle inhibitors with increased selectivity for cancer cellsSteven J Berthel
Discovery Chemistry, Roche Research Center, Hoffmann-La Roche Inc, Nutley, NJ 07110, USA
Anticancer Drugs 13:359-66. 2002..Limited exploration of structure-activity relationships involving side chain length, and aryl and pyridine rings allowed for the identification of more potent analogs...
Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapyChristian Tovar
Roche Research Center, Hoffmann-La Roche Inc, Nutley, NJ 07110, USA
Proc Natl Acad Sci U S A 103:1888-93. 2006..Nutlin-3 also showed good efficacy against tumors with normal MDM2 expression, suggesting that many of the patients with wild-type p53 tumors may benefit from antagonists of the p53-MDM2 interaction...- Elevated MDM2 boosts the apoptotic activity of p53-MDM2 binding inhibitors by facilitating MDMX degradationMingxuan Xia
Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, New Jersey 07110, USA
Cell Cycle 7:1604-12. 2008.... - Phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosisThelma Thompson
Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, 340 Kingsland St, Nutley, NJ 07110, USA
J Biol Chem 279:53015-22. 2004..We conclude that p53 phosphorylation on six major serine sites is not required for activation of p53 target genes or biological responses in vivo... - High-throughput screening for inhibitors of the Cks1-Skp2 interactionKuo Sen Huang
Discovery Technologies, Hoffmann La Roche, Inc, Nutley, New Jersey, USA
Methods Enzymol 399:717-28. 2005.... - MDM2 antagonists boost antitumor effect of androgen withdrawal: implications for therapy of prostate cancerChristian Tovar
Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
Mol Cancer 10:49. 2011..Here, we test this hypothesis in vitro and in vivo using the MDM2 antagonist, nutlin-3 and the p53 wild-type prostate cancer cell line, LNCaP... - Reduced transcriptional activity in the p53 pathway of senescent cells revealed by the MDM2 antagonist nutlin-3Baoying Huang
Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
Aging (Albany NY) 1:845-54. 2009.... - Cell cycle synchronization at the G2/M phase border by reversible inhibition of CDK1Lyubomir T Vassilev
Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, New Jersey 07110, USA
Cell Cycle 5:2555-6. 2006..RO-3306 arrested cells enter mitosis rapidly after release from the G2 block thus allowing for isolation of mitotic cells without microtubule poisons. RO-3306 represents a new molecular tool for studying CDK1 function in human cells... - MDM2 inhibitors for cancer therapyLyubomir T Vassilev
Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
Trends Mol Med 13:23-31. 2007..Here, the new developments in the quest for pharmacological p53 activators are reviewed with an emphasis on small-molecule inhibitors of the p53-MDM2 interaction... - Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1Lyubomir T Vassilev
Departments of Discovery Oncology and Discovery Chemistry, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
Proc Natl Acad Sci U S A 103:10660-5. 2006..Although CDK1 inhibition for up to 24 h is well tolerated, longer exposure to the inhibitor induces apoptosis in tumor cells, suggesting that selective CDK1 inhibitors may have utility in cancer therapy... - Cell-based screening approach for antitumor drug leads which exploits sensitivity differences between normal and cancer cells: identification of two novel cell-cycle inhibitorsL T Vassilev
Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
Anticancer Drug Des 16:7-17. 2001..Two of the compounds representing novel mitotic inhibitors with in vivo potency against established breast cancer xenografts (MDA-MB-435) are reported here... - p53 Activation by small molecules: application in oncologyLyubomir T Vassilev
Discovery Oncology, Roche Research Center, Hoffmann-La Roche Inc, Nutley, New Jersey 07110, USA
J Med Chem 48:4491-9. 2005 - In vivo activation of the p53 pathway by small-molecule antagonists of MDM2Lyubomir T Vassilev
Department of Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
Science 303:844-8. 2004..These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice... 
Pharmacologic p53 activation blocks cell cycle progression but fails to induce senescence in epithelial cancer cellsBaoying Huang
Discovery Oncology, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
Mol Cancer Res 7:1497-509. 2009..However, elevated expression of several inflammatory cytokines in cancer cells with nutlin-induced senescence-like phenotype suggests a possible in vivo benefit of p53-activating therapies...- Activation of p53 by MDM2 antagonists can protect proliferating cells from mitotic inhibitorsDaisy Carvajal
Discovery Oncology, Roche Research Center, Hoffmann-La Roche Inc, Nutley, New Jersey 07110, USA
Cancer Res 65:1918-24. 2005..Second, pretreatment with MDM2 antagonists before chemotherapy of tumors with mutant p53 may offer a partial protection to proliferating normal tissues... - Targeting protein-protein interactions for cancer therapyDavid C Fry
Structural Chemistry Group, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
J Mol Med (Berl) 83:955-63. 2005..The analysis focuses primarily on the structural characteristics of the participating binding sites, particularly the dimensions of the sites. Known ligands are also examined, especially with regard to their druglikeness... - Synthesis and evaluation of pyrido-thieno-pyrimidines as potent and selective Cdc7 kinase inhibitorsChunlin Zhao
Discovery Chemistry, Research Center, Roche, Nutley, NJ 07110, USA
Bioorg Med Chem Lett 19:319-23. 2009..Synthesis of a focused pyrido-thieno-pyrimidine library yielded potent and selective Cdc7 inhibitors with antiproliferative activity against cancer cells in vitro. Their synthesis and SAR data are presented herein... - Small-molecule antagonists of p53-MDM2 binding: research tools and potential therapeuticsLyubomir T Vassilev
Roche Research Center, Hoffman La Roche Inc, Nutley, New Jersey 07110, USA
Cell Cycle 3:419-21. 2004..Their potent activity against osteosarcoma xenografts suggests that MDM2 antagonists may have clinical utility in the treatment of tumors with wild-type p53... - A generic time-resolved fluorescence assay for serine/threonine kinase activity: application to Cdc7/Dbf4Kui Xu
Roche Research Center, Hoffmann-La Roche Inc, Nutley, NJ 07110, USA
J Biochem Mol Biol 36:421-5. 2003..Using this approach, we developed an assay for Cdc7/Dbf4 kinase activity, determined the K(m) for ATP, and identified rottlerin as a non-ATP competitive inhibitor of this enzyme... - Synthesis and activity of quinolinyl-methylene-thiazolinones as potent and selective cyclin-dependent kinase 1 inhibitorsShaoqing Chen
Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
Bioorg Med Chem Lett 17:2134-8. 2007..Representative compounds from this class reversibly inhibit CDK1 activity in vitro, and block cell cycle progression in human tumor cell lines, suggesting a potential use as antitumor agents... - p21 does not protect cancer cells from apoptosis induced by nongenotoxic p53 activationM Xia
Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
Oncogene 30:346-55. 2011..Taken together our results suggest that p21 induction does not affect the apoptotic response to nongenotoxic p53 activation... - 1,25-dihydroxyvitamin D3 enhances the apoptotic activity of MDM2 antagonist nutlin-3a in acute myeloid leukemia cells expressing wild-type p53Thelma Thompson
Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, New Jersey, USA
Mol Cancer Ther 9:1158-68. 2010.... - Protein-protein interactions involved in the recognition of p27 by E3 ubiquitin ligaseKui Xu
Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
Biochem J 371:957-64. 2003..Cks1 does not bind directly to the p27 phosphopeptide or to Skp1, which confirms its suggested role as an allosteric effector of Skp2... - Development of E3-substrate (MDM2-p53)-binding inhibitors: structural aspectsDavid C Fry
Structural Chemistry Group, Hoffmann-La Roche, Inc, Nutley, New Jersey, USA
Methods Enzymol 399:622-33. 2005..These tools are likely to be useful in any attempt to find and develop druglike compounds that modulate the function of a protein-protein interaction... - Macrophage inhibitory cytokine-1: a novel biomarker for p53 pathway activationHong Yang
Discovery Oncology, Roche Research Center, Hoffmann-La Roche Inc, Nutley, NJ 07110, USA
Mol Cancer Ther 2:1023-9. 2003..Estimation of MIC-1 concentration, both in vivo and in vitro, represents a novel tool for the study of p53 pathway and development of p53-activating therapeutics... - Induction of p53-dependent senescence by the MDM2 antagonist nutlin-3a in mouse cells of fibroblast originAlejo Efeyan
Molecular Oncology Program, Spanish National Cancer Research Center CNIO, Madrid, Spain
Cancer Res 67:7350-7. 2007..Our current results suggest that senescence could be a major cellular outcome of cancer therapy by antagonists of the p53-MDM2 interaction, such as nutlin-3a... - Enhanced tumor cell kill by combined treatment with a small-molecule antagonist of mouse double minute 2 and adenoviruses encoding p53Harm C A Graat
Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands
Mol Cancer Ther 6:1552-61. 2007..These findings suggest that Nutlins are promising compounds to be combined with p53 gene therapy and oncolytic virotherapy for cancer... - Depletion of mutant p53 and cytotoxicity of histone deacetylase inhibitorsMikhail V Blagosklonny
New York Medical College, Valhalla, New York 12208, USA
Cancer Res 65:7386-92. 2005..In a broader perspective, this shows how selectivity may be achieved by targeting a non-cancer-specific target, such as histone deacetylases, in the presence of a cancer-specific alteration, such as mutant p53... - Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myelomaThorsten Stühmer
Department of Internal Medicine II, Division of Hematology and Oncology, University Clinics Würzburg, Germany
Blood 106:3609-17. 2005..Therefore, MDM2 antagonists may offer a new treatment option for this disease... - MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cellsLlorenç Coll-Mulet
Departament de Ciències Fisiològiques II, IDIBELL Universitat de Barcelona, Campus de Bellvitge, Pavelló de Govern, 4a planta, E 08907 L Hospitalet de Llobregat, Barcelona, Spain
Blood 107:4109-14. 2006..These results suggest that MDM2 antagonists alone or in combination with chemotherapeutic drugs may offer a new treatment option for B-CLL... - Triptolide sensitizes AML cells to TRAIL-induced apoptosis via decrease of XIAP and p53-mediated increase of DR5Bing Z Carter
The University of Texas M D Anderson Cancer Center, Housto 77030, USA
Blood 111:3742-50. 2008..Thus, the combination of triptolide and TRAIL may provide a novel strategy for treating AML by overcoming critical mechanisms of apoptosis resistance... - p53-mediated apoptosis of CLL cells: evidence for a transcription-independent mechanismAndrew J Steele
Department of Hematology, Royal Free and University College Medical School, London, United Kingdom
Blood 112:3827-34. 2008..Therefore, strategies that block up-regulation of p53-mediated transcription may be of value in enhancing apoptosis induction of CLL cells by p53-elevating drugs... - MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapyKensuke Kojima
Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 448, Houston, TX 77030, USA
Blood 106:3150-9. 2005..p53 activation by targeting the p53-MDM2 interaction might offer a novel therapeutic strategy for AML that retain wild-type p53...