Medvet Science Pty Ltd

University of South Australia

Central Adelaide Local Health Network Inc.

Joanna Woodcock

Angel Francisco Lopez

Christopher James Bagley

Michael William Parker

Stuart Maxwell Pitson

William John McKinstry

Jamie Rossjohn

Carl Coolen

Michael Susithiran Samuel

The present disclosure relates to modulators of 14-3-3 functionality and their use in methods and compositions for preventing and/or treating various diseases, conditions and states, such as cancer and healing of wounds. Certain embodiments of the present disclosure provide a method of preventing and/or treating a disease, condition or state in a subject associated with altered 14-3-3 protein functionality and/or which would benefit from altering 14-3-3 functionality, the method comprising administering to the subject an effective amount of an agent which inhibits dimerization of the 14-3-3 protein, thereby preventing and/or treating the disease, condition or state in the subject.

Modulators of 14-3-3 functionality 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

A therapeutic agent capable of of binding to the F'-G&#x2032; loop of domain 4 of the commonChain of the receptor for GM-CSF, IL-3, and IL-5. The amino acid Tyrwhich is located in the F&#x2032;-G&#x2032; loop is critical in the high affinity binding and stimulation of function of GM-CSF, IL-3 and IL-5 to the commonchain of the receptors. Other receptors for cytokines also show hydrophobic amino acids in analogous positions and it is probable that they too play a pivotal role in binding of respective cytokines to them and in modulating function. Agents capable of binding to the F&#x2032;-G&#x2032; loops are suggested and should be of therapeutic value.

Therapeutic agents as cytokine antagonists and agonists

A therapeutic agent capable of of binding to the F&prime;-G&prime; loop of domain 4 of the common,Chain of the receptor for GM-CSF, IL-3, and IL-5. The amino acid Tyr,which is located in the F&prime;-G&prime; loop is critical in the high affinity binding and stimulation of function of GM-CSF, IL-3 and IL-5 to the common,chain of the receptors. Other receptors for cytokines also show hydrophobic amino acids in analogous positions and it is probable that they too play a pivotal role in binding of respective cytokines to them and in modulating function. Agents capable of binding to the F&prime;-G&prime; loops are suggested and should be of therapeutic value.

Growing community of inventors

Crafers, Australia

Joanna Woodcock