Alexei Degterev

Summary

Affiliation: Tufts University
Country: USA

Publications

  1. doi request reprint Identification of RIP1 kinase as a specific cellular target of necrostatins
    Alexei Degterev
    Tufts University, School of Medicine, Department of Biochemistry, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
    Nat Chem Biol 4:313-21. 2008
  2. pmc Akt Regulates TNFα synthesis downstream of RIP1 kinase activation during necroptosis
    Colleen R McNamara
    Graduate Program in Biochemistry, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachussets, United States of America
    PLoS ONE 8:e56576. 2013
  3. pmc Fluorescence polarization assay for inhibitors of the kinase domain of receptor interacting protein 1
    Jenny L Maki
    Department of Biochemistry, School of Medicine, Tufts University, Boston, MA 02111, USA
    Anal Biochem 427:164-74. 2012
  4. pmc Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway
    Junichi Hitomi
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Cell 135:1311-23. 2008
  5. pmc A HPLC method for the quantitative determination of N-(2-hydroxy-5-nitrophenylcarbamothioyl)-3,5-dimethylbenzamide in biological samples
    Igor Skidan
    Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 879:1610-6. 2011
  6. pmc Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains
    Benchun Miao
    Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02111, USA
    Proc Natl Acad Sci U S A 107:20126-31. 2010
  7. pmc Lanatoside C sensitizes glioblastoma cells to tumor necrosis factor-related apoptosis-inducing ligand and induces an alternative cell death pathway
    Christian E Badr
    Neuroscience Center and Molecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
    Neuro Oncol 13:1213-24. 2011
  8. pmc A genome-wide RNAi screen reveals multiple regulators of caspase activation
    Caroline H Yi
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 179:619-26. 2007
  9. pmc Expression and purification of active receptor interacting protein 1 kinase using a baculovirus system
    Jenny L Maki
    Department of Biochemistry, School of Medicine, Tufts University, Boston, MA 02111, USA
    Protein Expr Purif 89:156-61. 2013
  10. pmc In vitro cytotoxicity of novel pro-apoptotic agent DM-PIT-1 in PEG-PE-based micelles alone and in combination with TRAIL
    Igor Skidan
    Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA
    Drug Deliv 16:45-51. 2009

Collaborators

  • G D Cuny
  • Junying Yuan
  • Vladimir Torchilin
  • Noboru Mizushima
  • Yong Zhang
  • Christian E Badr
  • Jing Fan
  • Thomas Wurdinger
  • Bakhos A Tannous
  • Xiaobo Zhou
  • Tao Lu
  • Derek Abbott
  • Mamoru Shibata
  • Marcy MacDonald
  • Xin Teng
  • Benchun Miao
  • Jenny L Maki
  • Igor Skidan
  • Robert D Riehle
  • Heather Keys
  • Sinziana Cornea
  • Colleen R McNamara
  • Dimitry Ofengeim
  • Jinsheng Yang
  • Gerhard Wagner
  • Weihong Zheng
  • Junichi Hitomi
  • Zerong You
  • Chengye Yuan
  • Emily Hsu
  • Dana E Christofferson
  • Nathan J Moerke
  • Caroline H Yi
  • Ke Wang
  • Prakash G Jagtap
  • Sungwoon Choi
  • J Tres Brazell
  • Ruchita Ahuja
  • Douglas Barrows
  • Scott Gerber
  • Arminja Kettenbach
  • Awo D Osafo-Addo
  • Elizabeth E Smith
  • Manuela Polydoro
  • Xiaofeng Xia
  • Peng Shi
  • Soumya S Ray
  • Tadafumi Hashimoto
  • Marta M Lipinski
  • Yubo Fan
  • Stephen T C Wong
  • Ritesh Thekkedath
  • Jacob Grunwald
  • Tres Brazell
  • Kai Long
  • Mikhail Reibarkh
  • Kulbhushan A Durugkar
  • Brian Schaffhausen
  • C V Ramana
  • Jenny Maki
  • Alexey Lugovskoy
  • Parita Dholakia
  • Ritesh V Thekkedath
  • Ramnik J Xavier
  • Jianhua Yao
  • Michael A Moskowitz
  • Aylwin Ng
  • Sean I Savitz
  • Michael J Whalen
  • Arumugasamy Jeevanandam
  • Sonia Cantel
  • Michael Chorev
  • John A Porco
  • Jose A Halperin
  • John D Gross
  • Huseyin Aktas
  • Michael Boyce
  • Jinfeng Li
  • Dodzie K Sogah
  • Mikhail Y Reibarkh
  • Han Chen
  • Amr Fahmy
  • Prakash Jagtap
  • Régine Denu
  • Xuechao Xing

Detail Information

Publications28

  1. doi request reprint Identification of RIP1 kinase as a specific cellular target of necrostatins
    Alexei Degterev
    Tufts University, School of Medicine, Department of Biochemistry, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
    Nat Chem Biol 4:313-21. 2008
    ..Overall, our data establish necrostatins as the first-in-class inhibitors of RIP1 kinase, the key upstream kinase involved in the activation of necroptosis...
  2. pmc Akt Regulates TNFα synthesis downstream of RIP1 kinase activation during necroptosis
    Colleen R McNamara
    Graduate Program in Biochemistry, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachussets, United States of America
    PLoS ONE 8:e56576. 2013
    ..Overall, our results provide new insights into the mechanism of necroptosis and the role of Akt kinase in both cell death and inflammatory regulation...
  3. pmc Fluorescence polarization assay for inhibitors of the kinase domain of receptor interacting protein 1
    Jenny L Maki
    Department of Biochemistry, School of Medicine, Tufts University, Boston, MA 02111, USA
    Anal Biochem 427:164-74. 2012
    ..62 (fluorescein-Nec-1) and 0.57 (fluorescein-Nec-3). In addition, results obtained from the FP assays and ligand docking studies provide insights into the putative binding sites of Nec-1, Nec-3, and Nec-4...
  4. pmc Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway
    Junichi Hitomi
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Cell 135:1311-23. 2008
    ..Our study defines a cellular signaling network that regulates necroptosis and the molecular bifurcation that controls apoptosis and necroptosis...
  5. pmc A HPLC method for the quantitative determination of N-(2-hydroxy-5-nitrophenylcarbamothioyl)-3,5-dimethylbenzamide in biological samples
    Igor Skidan
    Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 879:1610-6. 2011
    ....
  6. pmc Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains
    Benchun Miao
    Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02111, USA
    Proc Natl Acad Sci U S A 107:20126-31. 2010
    ..Overall, our studies demonstrate the feasibility of developing specific small molecule antagonists of PIP3 signaling...
  7. pmc Lanatoside C sensitizes glioblastoma cells to tumor necrosis factor-related apoptosis-inducing ligand and induces an alternative cell death pathway
    Christian E Badr
    Neuroscience Center and Molecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
    Neuro Oncol 13:1213-24. 2011
    ..Activation of such mechanism may be a useful strategy to counter resistance of cancer cells to apoptosis...
  8. pmc A genome-wide RNAi screen reveals multiple regulators of caspase activation
    Caroline H Yi
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 179:619-26. 2007
    ..Our data suggest a previously unappreciated fundamental connection between various cellular processes and caspase-dependent cell death...
  9. pmc Expression and purification of active receptor interacting protein 1 kinase using a baculovirus system
    Jenny L Maki
    Department of Biochemistry, School of Medicine, Tufts University, Boston, MA 02111, USA
    Protein Expr Purif 89:156-61. 2013
    ..The recombinant protein displayed kinase activity that was blocked by RIP1 inhibitors, necrostatins. The purified protein was used to develop a simple and robust thermal shift assay for further assessment of RIP1 inhibitors...
  10. pmc In vitro cytotoxicity of novel pro-apoptotic agent DM-PIT-1 in PEG-PE-based micelles alone and in combination with TRAIL
    Igor Skidan
    Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA
    Drug Deliv 16:45-51. 2009
    ..In conclusion, DM-PIT-1 micellar preparations can be used for targeted combination therapy against TRAIL-resistant cancers...
  11. doi request reprint Expansion and evolution of cell death programmes
    Alexei Degterev
    Tufts University, School of Medicine, Department of Biochemistry, 136 Harrison Ave, Boston, Massachusetts 02111, USA
    Nat Rev Mol Cell Biol 9:378-90. 2008
    ..Here we examine how and why these different cell death programmes have evolved, with an eye towards new cytoprotective therapeutic opportunities...
  12. doi request reprint Role of phosphatidylinositol 3,4,5-trisphosphate in cell signaling
    Robert D Riehle
    Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, 02115, USA
    Adv Exp Med Biol 991:105-39. 2013
    ..Additionally, recent attempts at targeting PtdIns(3,4,5)P3 signaling via small molecule inhibitors are summarized...
  13. pmc Identification of small molecule inhibitors of neurite loss induced by Aβ peptide using high content screening
    Dimitry Ofengeim
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 287:8714-23. 2012
    ..Overall, our work establishes the feasibility of identifying small molecule inhibitors of Aβ-induced neurite loss using the NeuriteIQ pipeline and provides novel insights into the mechanisms of neuroprotection by NSAIDs...
  14. ncbi request reprint Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G
    Nathan J Moerke
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Cell 128:257-67. 2007
    ..The identification of this compound provides a new tool for studying translational control and establishes a possible new strategy for cancer therapy...
  15. ncbi request reprint Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1
    Mamoru Shibata
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 281:14474-85. 2006
    ..100, 15077-15082), we propose that the age-dependent decrease of beclin 1 expression may lead to a reduction of autophagic activity during aging, which in turn promotes the accumulation of mutant Htt and the progression of the disease...
  16. ncbi request reprint Targeting phospshatidylinositol 3-kinase signaling with novel phosphatidylinositol 3,4,5-triphosphate antagonists
    Benchun Miao
    Department of Biochemistry, Tufts University School of Medicine, Boston, MA, USA
    Autophagy 7:650-1. 2011
    ....
  17. pmc Automated neurite extraction using dynamic programming for high-throughput screening of neuron-based assays
    Yong Zhang
    Center for Bioinformatics, Harvard Center for Neurodegeneration and Repair, Harvard Medical School, Boston, MA 02215, USA
    Neuroimage 35:1502-15. 2007
    ..All these properties make the proposed algorithm attractive for high-throughput screening of neuron-based assays...
  18. doi request reprint Methods to analyze cellular necroptosis
    Benchun Miao
    Department of Biochemistry, Tufts University School of Medicine, Boston, MA, USA
    Methods Mol Biol 559:79-93. 2009
    ..Herein, we describe the methods to analyze cellular necroptosis, and the methods to analyze the inhibitory effects of anti-necroptosis compounds (necrostatin-1)...
  19. ncbi request reprint Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
    Alexei Degterev
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Chem Biol 1:112-9. 2005
    ..Our study identifies a previously undescribed basic cell-death pathway with potentially broad relevance to human pathologies...
  20. doi request reprint Micellar formulations of pro-apoptotic DM-PIT-1 analogs and TRAIL in vitro and in vivo
    Robert D Riehle
    Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA
    Drug Deliv 20:78-85. 2013
    ..These results indicate the utility of delivering TRAIL and PI3K pathway inhibitors in a combined micellar preparation...
  21. doi request reprint Activity assays for receptor-interacting protein kinase 1:a key regulator of necroptosis
    Jenny L Maki
    Department of Biochemistry, School of Medicine, Tufts University, Boston, MA, USA
    Methods Mol Biol 1004:31-42. 2013
    ..Here, we describe RIP1 protein expression and purification from mammalian and insect cells as well as two in vitro kinase assays to detect RIP1 kinase activity and inhibition...
  22. pmc Necrostatin-1 reduces histopathology and improves functional outcome after controlled cortical impact in mice
    Zerong You
    Neuroscience Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Cereb Blood Flow Metab 28:1564-73. 2008
    ..The data suggest that necroptosis plays a significant role in the pathogenesis of cell death and functional outcome after TBI and that necrostatin-1 may have therapeutic potential for patients with TBI...
  23. ncbi request reprint Structure-activity relationship analysis of a novel necroptosis inhibitor, Necrostatin-5
    Ke Wang
    State Key Laboratory of Bio organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
    Bioorg Med Chem Lett 17:1455-65. 2007
    ..Here, we describe a series of structural modifications of Nec-5 and the structure-activity relationship (SAR) of Nec-5 series in inhibiting necroptosis...
  24. ncbi request reprint Structure-activity relationship study of tricyclic necroptosis inhibitors
    Prakash G Jagtap
    Laboratory for Drug Discovery in Neurodegeneration, Harvard Center for Neurodegeneration and Repair, Brigham and Women s Hospital and Harvard Medical School, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA
    J Med Chem 50:1886-95. 2007
    ..Amides at the 2-position of the tricyclic ring were best. The Nec-3 series provides new tools for elucidating caspase-independent cell death pathways and potentially lead compounds for therapeutic development...
  25. pmc Structure-activity relationship study of [1,2,3]thiadiazole necroptosis inhibitors
    Xin Teng
    Laboratory for Drug Discovery in Neurodegeneration, Harvard Center for Neurodegeneration and Repair, Brigham and Women s Hospital and Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 17:6836-40. 2007
    ..Finally, replacement of the [1,2,3]thiadiazole with a variety of thiophene derivatives was tolerated, although some erosion of potency was observed...
  26. pmc Structure-activity relationship and liver microsome stability studies of pyrrole necroptosis inhibitors
    Xin Teng
    Laboratory for Drug Discovery in Neurodegeneration, Harvard NeuroDiscovery Center, Brigham and Women s Hospital and Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 18:3219-23. 2008
    ....
  27. doi request reprint Structure-activity relationship study of a novel necroptosis inhibitor, necrostatin-7
    Weihong Zheng
    State Key Laboratory of Bio organic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
    Bioorg Med Chem Lett 18:4932-5. 2008
    ..Here, we describe a series of structural modifications and the structure-activity relationship (SAR) of the Nec-7 series for inhibiting necroptosis...
  28. ncbi request reprint Structure-activity relationship study of novel necroptosis inhibitors
    Xin Teng
    Laboratory for Drug Discovery in Neurodegeneration, Harvard Center for Neurodegeneration and Repair, Brigham and Women s Hospital and Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 15:5039-44. 2005
    ..A representative member of this compound class demonstrated moderate pharmacokinetic characteristics and readily entered the central nervous system upon intravenous administration...

Research Grants7

  1. Caspase-independent cell death and neurodegeneration
    Alexei Degterev; Fiscal Year: 2006
    ..Dr. Alexei Degterev is aspiring to become a fully independent research scientist in the field of aging-associated neuronal cell ..
  2. Mechanistic analysis of necrostatins: specific inhibitors of programmed necrosis
    Alexei Degterev; Fiscal Year: 2009
    ..These molecules may present a principally novel direction for drug development for many devastating human disorders. ..
  3. Molecular and functional analysis of necroptosis initiation complex
    Alexei Degterev; Fiscal Year: 2009
    ..Our proposal aims to provide further understanding of the molecular mechanism of necroptosis, which would allow us to take full advantage of this exciting discovery for development of new therapies. ..
  4. Mechanistic analysis of necrostatins: specific inhibitors of programmed necrosis
    Alexei Degterev; Fiscal Year: 2010
    ..These molecules may present a principally novel direction for drug development for many devastating human disorders. ..
  5. Mechanistic analysis of necrostatins: specific inhibitors of programmed necrosis
    Alexei Degterev; Fiscal Year: 2009
    ..These molecules may present a principally novel direction for drug development for many devastating human disorders. ..
  6. Molecular and functional analysis of necroptosis initiation complex
    Alexei Degterev; Fiscal Year: 2010
    ..Our proposal aims to provide further understanding of the molecular mechanism of necroptosis, which would allow us to take full advantage of this exciting discovery for development of new therapies. ..