PYC pyc therapeutics limited

article in peer reviewed journal, page-2

  1. SoT
    858 Posts.
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    Here’s a summary and some background to the article:

    The lead authors are Kevin Ngoei (Dept of Biochemistry and Molecular Biology, University of Melbourne) and Bruno Catimel (The Ludwig Institute for Cancer Research).
    Marie Bogoyevitch heads the research team that Kevin Ngoei is part of, at the Dept of Biochemistry and Molecular Biology, University of Melbourne, and she is also a long time member of Phylogica’s Scientific Advisory Board.
    Nadia Milech and Paul Watt are Phylogica.

    This research is targeting an intracellular communication pathway ‘the c-Jun N-terminal Kinase (JNK) subfamily’ that has been linked to diseases including stroke, obesity and diabetes.

    Three major points of the article:
    - they were able to inhibit JNK1 activity toward c-Jun, with an 18 amino acid peptide (L-PYC98). They then used the ‘retro-inverso’ form of this peptide (D-PYC98) and achieved a 5-fold increase in potency.
    - A significant feature of this peptide was it’s preference in actions to inhibit JNK-mediated substrate phosphorylation. To date, there has been little evidence for substrate-selectivity for JNK inhibitors.
    - (D-PYC98) also targeted p38(alpha). p38 is a pathway that ranges from acute cardiovascular disease and hypoxia-induced Alzheimers disease, to breast cancer cell invasion.

    The article finishes with: “Clearly, the structural mechanisms underlying the inhibition of both JNK1 and p38 will require more detailed structural work, but will also provide new insights into the potential to develop novel dual-target protein kinase inhibitors.

    SoT
 
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