Method for identifying a modulator of the TNFα or CD40L interaction with their cognate receptors
AssigneeUcb Biopharma Srl
InventorsJames Philip O'Connell, John Robert Porter, Alastair Lawson, Boris Kroeplien, Stephen Edward Rapecki, Timothy John Norman, Graham John Warrellow
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Abstract
It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Accordingly, these compounds can be used as modulators of TNF. A new assay for identifying compounds with this mechanism of action is also disclosed.
Claims17
A method for identifying a compound that is capable of binding to trimeric TNFα or CD40L, whereby the compound-trimer complex binds to the requisite TNF superfamily receptor and modulates the signalling of the receptor, comprising:
- a) performing a receptor-ligand binding assay in which a sample of the TNFα or CD40L trimers and the compound is applied to the requisite TNF receptor;
- b) comparing the binding of the TNFα or CD40L trimer-compound complex to the requisite TNF receptor with a control sample, wherein the control sample comprises TNFα or CD40L trimers in the absence of compound;
- and
- c) selecting a compound that enhances the binding of the TNFα or CD40L trimers to the receptor compared to the binding of the TNFα or CD40L trimers to the receptor in the control sample, and wherein the method further comprises contacting the requisite receptors with both the TNFα or CD40L and the compound-trimer complex and detecting whether the test compound prevents or reduces the TNFα or CD40L trimer signaling through the requisite TNF superfamily receptor.
Dependencies are inferred from the claim text.