Medvet Science Pty Ltd

Cytopia Research Pty Ltd

Jamie Rossjohn

Andrew Frederick Wilks

Christopher John Burns

Angel Francisco Lopez

Emmanuelle Fantino

Michael William Parker

Joanna Woodcock

Christopher James Bagley

Michelle Leanne Styles

William John McKinstry

Isabelle Lucet

The present invention relates to X-ray crystallography studies of a human Janus Kinase 2 (JAK2) domain. More particularly, it relates to the crystal structure of a JAK2 kinase domain bound to a inhibitor. The invention further relates to the use of the crystal and related structural information to select and screen for compounds that interact with JAK2 and related proteins and to compounds that could be used for the treatment of diseases mediated by inappropriate JAK2 activity.

Crystal structure of human Janus Kinase 2 (JAK2) and uses thereof

The present invention provides a cytokine-binding domain or portion thereof which binds to at least one cytokine and is capable of transducing a cytokine signal through a single cytokine receptor, said domain comprising a portion of the B'-C&#x2032; loop of domain 4 of a &#x3b2;chain or analogous structure of a cytokine receptor. In another aspect of the invention there is provided a method of identifying a compound having cytokine agonist or antagonist activity, said method including subjecting a potential cytokine agonist and/or cytokine antagonist compound to a cytokine binding domain or portion thereof wherein said domain binds to at least one cytokine and is capable of transducing a cytokine signal through a single cytokine receptor, said domain comprising a portion of the B&#x2032;-C&#x2032; loop of domain 4 of a &#x3b2;chain or analogous structure of the cytokine receptor; and determining the presence of an agonist or antagonist response of the compound on the activity of a cytokine. In a preferred aspect there is provided a method fo identifying a GM-CSF, IL-3 and IL-5 agonist or antagonist, said method including: subjecting a potential agonist or antagonist to a GM-CSF, IL-3 and IL-5 binding domain or portion thereof wherein said domain binds to at least one of the cytokines and is capable of transducing a cytokine signal through a single cytokine receptor, said domain comprising a portion of the B&#x2032;-C&#x2032; loop of domain 4 of a &#x3b2;chain or analogous structure of the cytokine receptor; and determining the presence of a agonist or antagonist response from the compound on the activity of GM-CSF, IL-3 and IL-5.

Cytokine binding domain of cytokine receptors

Growing community of inventors

Carnegie, Australia

Jamie Rossjohn