1. Dual role of Src kinase in governing neuronal survival

    Brain Research 1594:1 (2015)

    Background Src-family kinases (SFKs) are involved in neuronal survival and their aberrant regulation contributes to neuronal death. However, how they control neuronal survival and death remains unclear.
  2. Dual role of Src kinase in governing neuronal survival.

    Brain research 1594:1 (2015) PMID 25451123

    Src-family kinases (SFKs) are involved in neuronal survival and their aberrant regulation contributes to neuronal death. However, how they control neuronal survival and death remains unclear. To define the effect of inhibition of Src activity and expression on neuronal survival. In agreement wit...
  3. Dual role of Src kinase in governing neuronal survival.

    Brain research 1594:1 (2015) PMID 25451123

    Src-family kinases (SFKs) are involved in neuronal survival and their aberrant regulation contributes to neuronal death. However, how they control neuronal survival and death remains unclear. To define the effect of inhibition of Src activity and expression on neuronal survival. In agreement wit...
  4. Dual role of Src kinase in governing neuronal survival

    Brain Research 1594:1 (2015)

    Background Src-family kinases (SFKs) are involved in neuronal survival and their aberrant regulation contributes to neuronal death. However, how they control neuronal survival and death remains unclear.
  5. Dual role of Src kinase in governing neuronal survival

    Brain Research 1594:1 (2015)

    Background Src-family kinases (SFKs) are involved in neuronal survival and their aberrant regulation contributes to neuronal death. However, how they control neuronal survival and death remains unclear.
  6. Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production.

    Cell 159(7):1549 (2014) PMID 25525874

    Activated caspases are a hallmark of apoptosis induced by the intrinsic pathway, but they are dispensable for cell death and the apoptotic clearance of cells in vivo. This has led to the suggestion that caspases are activated not just to kill but to prevent dying cells from triggering a host imm...
  7. Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death.

    PNAS 111(42):15072 (2014) PMID 25288762 PMCID PMC4210347

    Necroptosis is considered to be complementary to the classical caspase-dependent programmed cell death pathway, apoptosis. The pseudokinase Mixed Lineage Kinase Domain-Like (MLKL) is an essential effector protein in the necroptotic cell death pathway downstream of the protein kinase Receptor Int...
  8. Discovery of a Potent and Selective BCL-XL Inhibitor with in Vivo Activity.

    ACS Medicinal Chemistry Letters 5(10):1088 (2014) PMID 25313317 PMCID PMC4190639

    A-1155463, a highly potent and selective BCL-XL inhibitor, was discovered through nuclear magnetic resonance (NMR) fragment screening and structure-based design. This compound is substantially more potent against BCL-XL-dependent cell lines relative to our recently reported inhibitor, WEHI-539, ...
  9. Simplified silvestrol analogues with potent cytotoxic activity.

    Chemmedchem 9(7):1556 (2014) PMID 24677741

    The complex natural products silvestrol (1) and episilvestrol (2) are inhibitors of translation initiation through binding to the DEAD-box helicase eukaryotic initiation factor 4A (eIF4A). Both compounds are potently cytotoxic to cancer cells in vitro, and 1 has demonstrated efficacy in vivo in ...
  10. Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL.

    ACS Medicinal Chemistry Letters 5(6):662 (2014) PMID 24944740 PMCID PMC4060937

    Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirabl...
  11. A perspective on 10-years HTS experience at the Walter and Eliza Hall Institute of Medical Research - eighteen million assays and counting.

    Combinatorial Chemistry & High Throughput Scree... 17(3):241 (2014) PMID 24409955

    The Walter and Eliza Hall Institute of Medical Research (WEHI) is Australia's longest serving medical research institute. WEHI's High Throughput Screening (HTS) Facility was established in 2003 with $5 million of infrastructure funds invested by WEHI, and the Victorian State Government's Strateg...
  12. De-novo designed library of benzoylureas as inhibitors of BCL-XL: synthesis, structural and biochemical characterization.

    Journal of medicinal and pharmaceutical chemistry 57(4):1323 (2014) PMID 24456288

    The prosurvival BCL-2 proteins are attractive yet challenging targets for medicinal chemists. Their involvement in the initiation and progression of many, if not all, tumors makes them prime targets for developing new anticancer therapies. We present our approach based on de novo structure-based...
  13. Insights into the evolution of divergent nucleotide-binding mechanisms among pseudokinases revealed by crystal structures of human and mouse MLKL.

    Biochemical Journal 457(3):369 (2014) PMID 24219132

    The pseudokinase MLKL (mixed lineage kinase domain-like) was identified recently as an essential checkpoint in the programmed necrosis or 'necroptosis' cell death pathway. In the present study, we report the crystal structure of the human MLKL pseudokinase domain at 1.7 Å (1 Å=0.1 nm) resolution...
  14. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy.

    Nature Reviews: Molecular Cell Biology 15(1):49 (2014) PMID 24355989

    The BCL-2 protein family determines the commitment of cells to apoptosis, an ancient cell suicide programme that is essential for development, tissue homeostasis and immunity. Too little apoptosis can promote cancer and autoimmune diseases; too much apoptosis can augment ischaemic conditions and...
  15. Discovery of potent and selective benzothiazole hydrazone inhibitors of Bcl-XL.

    Journal of medicinal and pharmaceutical chemistry 56(13):5514 (2013) PMID 23767404

    Developing potent molecules that inhibit Bcl-2 family mediated apoptosis affords opportunities to treat cancers via reactivation of the cell death machinery. We describe the hit-to-lead development of selective Bcl-XL inhibitors originating from a high-throughput screening campaign. Small struct...
  16. Structure-guided design of a selective BCL-X(L) inhibitor.

    Nature Chemical Biology 9(6):390 (2013) PMID 23603658

    The prosurvival BCL-2 family protein BCL-X(L) is often overexpressed in solid tumors and renders malignant tumor cells resistant to anticancer therapeutics. Enhancing apoptotic responses by inhibiting BCL-X(L) will most likely have widespread utility in cancer treatment and, instead of inhibitin...
  17. Crystallization and preliminary X-ray characterization of Epstein-Barr virus BHRF1 in complex with a benzoylurea peptidomimetic.

    Acta Crystallographica Section F 68(Pt 12):1521 (2012) PMID 23192038 PMCID PMC3509979

    BHRF1 is a pro-survival Bcl-2 homologue encoded by Epstein-Barr virus (EBV) that plays a key role in preventing premature host cell death during viral infection and may contribute to the development of malignancies associated with chronic EBV infections. The anti-apoptotic action of BHRF1 is bas...
  18. Crystallization and preliminary X-ray characterization of Epstein-Barr virus BHRF1 in complex with a benzoylurea peptidomimetic.

    Acta Crystallographica Section F 68(Pt 12):1521 (2012) PMID 23192038 PMCID PMC3509979

    BHRF1 is a pro-survival Bcl-2 homologue encoded by Epstein-Barr virus (EBV) that plays a key role in preventing premature host cell death during viral infection and may contribute to the development of malignancies associated with chronic EBV infections. The anti-apoptotic action of BHRF1 is bas...
  19. Synthesis of conformationally constrained benzoylureas as BH3-mimetics.

    Organic & Biomolecular Chemistry 10(27):5230 (2012) PMID 22648632

    The design of small molecules that mimic the BH3 domain and bind to Bcl-2 proteins has emerged as a promising approach to discovering novel anti-cancer therapeutics. We reveal the design and synthesis of conformationally constrained benzoylurea scaffolds as conformational probes. Central to heli...
  20. BACE inhibitors as potential drugs for the treatment of Alzheimer's disease: focus on bioactivity.

    Recent patents on CNS drug discovery 6(2):91 (2011) PMID 21585329

    Current drug development for the treatment of Alzheimer's Disease is principally based on the amyloid cascade theory, and aims to reduce the levels of Aβ amyloid peptide in the brain. This can be achieved, either by decreasing peptide production through inhibition of β-secretase (also known as B...