Research Topics
| Luke WhitesellSummaryAffiliation: Massachusetts Institute of Technology Country: USA Publications
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Detail Information
Publications
The anticancer activity of the fungal metabolite terrecyclic acid A is associated with modulation of multiple cellular stress response pathwaysThomas J Turbyville
Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, The University of Arizona, Tucson, AZ 85706-6800, USA
Mol Cancer Ther 4:1569-76. 2005..Small-molecule natural products such as TCA may serve as useful probes for understanding the relationships between these pathways, potentially providing leads for the design of novel and effective anticancer drugs...- Actin microfilament aggregation induced by withaferin A is mediated by annexin IIRyan R Falsey
Nat Chem Biol 2:33-8. 2006.... - Inhibiting HSP90 to treat cancer: a strategy in evolutionL Whitesell
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
Curr Mol Med 12:1108-24. 2012..This review will focus on these fundamental issues with the goal of suggesting ways to make the clinical development of HSP90 inhibitors become less empiric and ultimately more successful... 
HSP90 as a platform for the assembly of more effective cancer chemotherapyLuke Whitesell
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
Biochim Biophys Acta 1823:756-66. 2012..This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90)...- HSP90 and the chaperoning of cancerLuke Whitesell
Steele Memorial Children s Research Center, University of Arizona, Tucson, Arizona 85724, USA
Nat Rev Cancer 5:761-72. 2005..Pharmacologically 'bribing' the essential guard duty of the chaperone HSP90 (heat-shock protein of 90 kDa) seems to offer a unique anticancer strategy of considerable promise... - Inhibiting the transcription factor HSF1 as an anticancer strategyLuke Whitesell
Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA
Expert Opin Ther Targets 13:469-78. 2009..The malignant lifestyle confers dependence on this 'non-oncogene', suggesting a therapeutic role for HSF1 inhibitors... 
Search for Hsp90 inhibitors with potential anticancer activity: isolation and SAR studies of radicicol and monocillin I from two plant-associated fungi of the Sonoran desertThomas J Turbyville
SW Center for Natural Products Research and Commercialization, University of Arizona, Tucson, Arizona 85706-6800, USA
J Nat Prod 69:178-84. 2006..Isolation of radicicol and monocillin I in this study provides evidence that we have developed an effective strategy for discovering natural product-based Hsp90 inhibitors with potential anticancer activity...- Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesisChengkai Dai
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Cell 130:1005-18. 2007..While it enhances organismal survival and longevity under most circumstances, HSF1 has the opposite effect in supporting the lethal phenomenon of cancer... - Overcoming fluconazole resistance in Candida albicans clinical isolates with tetracyclic indolesWillmen Youngsaye
Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Bioorg Med Chem Lett 22:3362-5. 2012..albicans, as determined in Saccharomyces cerevisiae models, and may be a useful probe to uncover alternative resistance pathways... - A new dihydroxanthenone from a plant-associated strain of the fungus Chaetomium globosum demonstrates anticancer activityE M Kithsiri Wijeratne
Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, The University of Arizona, 250 E. Valencia Road, Tucson, AZ 85706-6800, USA
Bioorg Med Chem 14:7917-23. 2006.... - Hsp90 inhibitors deplete key anti-apoptotic proteins in pediatric solid tumor cells and demonstrate synergistic anticancer activity with cisplatinRochelle Bagatell
Steele Memorial Children s Research Center and The Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA
Int J Cancer 113:179-88. 2005..Our findings suggest that Hsp90 inhibitors may prove useful either alone or as a component of multi-drug regimens in the treatment of neuroblastoma and osteosarcoma... - Loss of tumor suppressor NF1 activates HSF1 to promote carcinogenesisChengkai Dai
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
J Clin Invest 122:3742-54. 2012..The loss of NF1 function engages an evolutionarily conserved cellular survival mechanism that ultimately impairs survival of the whole organism by facilitating carcinogenesis... - Isolation, optimization of production and structure-activity relationship studies of monocillin I, the cytotoxic constituent of Paraphaeosphaeria quadriseptataE M Kithsiri Wijeratne
Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, University of Arizona, 250 E. Valencia Road, Tucson, Arizona 85706-6800, USA
J Antibiot (Tokyo) 57:541-6. 2004 - Altered Hsp90 function in cancer: a unique therapeutic opportunityRochelle Bagatell
Department of Pediatrics and Hematology/Oncology, Arizona Health Sciences Center, Room 5341, 1501 North Campbell Avenue, Tucson, AZ 85724, USA
Mol Cancer Ther 3:1021-30. 2004.... - Geopyxins A-E, ent-kaurane diterpenoids from endolichenic fungal strains Geopyxis aff. majalis and Geopyxis sp. AZ0066: structure-activity relationships of geopyxins and their analoguesE M Kithsiri Wijeratne
SW Center for Natural Products Research and Commercialization, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona, 250 E Valencia Road, Tucson, Arizona 85706, United States
J Nat Prod 75:361-9. 2012.... - A rhizosphere fungus enhances Arabidopsis thermotolerance through production of an HSP90 inhibitorCatherine A McLellan
FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA
Plant Physiol 145:174-82. 2007..Finally, cocultivation of P. quadriseptata with Arabidopsis enhanced plant heat stress tolerance. These data demonstrate that HSP90-inhibitory compounds produced by fungi can influence plant growth and responses to the environment... - HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancersMarc L Mendillo
The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Cell 150:549-62. 2012..Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications... - Inhibiting GPI anchor biosynthesis in fungi stresses the endoplasmic reticulum and enhances immunogenicityCatherine A McLellan
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
ACS Chem Biol 7:1520-8. 2012..Gwt1 is a promising antifungal drug target, and gepanacin is a useful probe for studying how disrupting GPI-anchor synthesis impairs viability and alters host-pathogen interactions in genetically intractable fungi... - Ponicidin and oridonin are responsible for the antiangiogenic activity of Rabdosia rubescens, a constituent of the herbal supplement PC SPESLinda C Meade-Tollin
Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, University of Arizona, 250 E. Valencia Road, Tucson, AZ 85706-6800, USA
J Nat Prod 67:2-4. 2004.... - Phase I pharmacokinetic and pharmacodynamic study of 17-N-allylamino-17-demethoxygeldanamycin in pediatric patients with recurrent or refractory solid tumors: a pediatric oncology experimental therapeutics investigators consortium studyRochelle Bagatell
Department of Pediatrics and Steele Children s Research Center, University of Arizona, Tucson, AZ 85724, USA
Clin Cancer Res 13:1783-8. 2007.... - 2,3-Dihydrowithaferin A-3beta-O-sulfate, a new potential prodrug of withaferin A from aeroponically grown Withania somniferaYa ming Xu
Southwest Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, The University of Arizona, 250 E Valencia Road, Tucson, AZ 85706, USA
Bioorg Med Chem 17:2210-4. 2009.... - Heat shock protein 90: a unique chemotherapeutic targetSara B Cullinan
The Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
Semin Oncol 33:457-65. 2006..In this review, we highlight the current understanding of Hsp90 biology as it relates to cancer and discuss the discovery, development, and clinical status of Hsp90 inhibitors as anticancer drugs... - HSP90: a rising star on the horizon of anticancer targetsChengkai Dai
Whitehead Institute for Biomedical Research, Room 649, 9 Cambridge Center, Cambridge, MA 02142, and University of Arizona, Steele Memorial Children s Research Center, Tucson, AZ 85724, USA
Future Oncol 1:529-40. 2005..Finally, it closes with a discussion of the unique challenges confronting the further development of these agents and their prospects for the future... - Cytotoxic constituents of Aspergillus terreus from the rhizosphere of Opuntia versicolor of the Sonoran DesertE M Kithsiri Wijeratne
SW Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, University of Arizona, 250 E. Valencia Road, Tucson, Arizona 85706-6800, USA
J Nat Prod 66:1567-73. 2003..A pathway for the biosynthetic origin of asterredione (1) from asterriquinone D (7) is proposed... - Piperazinyl quinolines as chemosensitizers to increase fluconazole susceptibility of Candida albicans clinical isolatesWillmen Youngsaye
Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Bioorg Med Chem Lett 21:5502-5. 2011..A piperazinyl quinoline was identified as a new small-molecule probe (ML189) satisfying these criteria... - The stress response: implications for the clinical development of hsp90 inhibitorsLuke Whitesell
Steele Memorial Children s Research Center, University of Arizona, Tucson, AZ 85724, USA
Curr Cancer Drug Targets 3:349-58. 2003..Lastly, stress response induction by Hsp90 inhibitors may have therapeutic benefits in non-neoplastic disorders such as heart disease, stroke and neurodegenerative diseases. These benefits are just beginning to be explored... - Hormone-refractory breast cancer remains sensitive to the antitumor activity of heat shock protein 90 inhibitorsJason Beliakoff
Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona 85724, USA
Clin Cancer Res 9:4961-71. 2003..In this context, combined treatment with 17AAG and Tam should be avoided because Tam may inhibit the ability of 17AAG to deplete the ER, potentially reducing its anticancer activity... - Two cases of pediatric neuroblastoma with tumor thrombus in the inferior vena cavaRochelle Bagatell
Department of Pediatrics and Steele Memorial Children s Research Center, Tucson, Arizona, USA
J Pediatr Hematol Oncol 24:397-400. 2002..In one patient a pulmonary embolus developed after initiation of cytotoxic therapy; the second patient was prophylactically anticoagulated and had no embolic event... - Design of quinolinedione-based geldanamycin analoguesRobert Hargreaves
Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287-1604, USA
Bioorg Med Chem Lett 13:3075-8. 2003..COMPARE analysis revealed that the LC(50) profile of 2-phenyl-6-(2-chloroethylamino)quinoline-5,8-dione has the highest geldanamycin-like activity (0.74 correlation coefficient)... - Hsp90: an emerging target for breast cancer therapyJason Beliakoff
Department of Urology, Stanford University School of Medicine, CA, USA
Anticancer Drugs 15:651-62. 2004..Given the redundancy and complexity of the molecular abnormalities present in most breast cancers, the ability of Hsp90 inhibitors to alter the activity of multiple oncogenic targets may prove of unique therapeutic benefit... - A phase I study of 17-allylaminogeldanamycin in relapsed/refractory pediatric patients with solid tumors: a Children's Oncology Group studyBrenda J Weigel
University of Minnesota Cancer Center and Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA
Clin Cancer Res 13:1789-93. 2007..To determine the recommended phase 2 dose, dose-limiting toxicities (DLT), pharmacokinetic profile, and pharmacodynamics of the heat shock protein (Hsp) 90 inhibitor, 17-allylaminogeldanamycin (17-AAG)...