TNF receptor signaling modulator assay
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.
Claims18
A method for identifying a compound that is capable of binding to a TNFα trimer to form a compound-trimer complex, whereby the compound-trimer complex binds to a TNF receptor and modulates the signalling of the receptor, comprising:
- measuring the stability of the TNFα trimer in a sample comprising the compound, comprising:
- a) determining the thermal transition midpoint (Tm) of the TNFα trimer in a sample of the TNFα trimer and the compound;
- b) comparing the Tm of the TNFα trimer in the sample with a control sample, wherein the control sample comprises the TNFα trimer in the absence of the compound, and wherein a higher Tm of the TNFα trimer in a sample of the TNFα trimer and the compound indicates that the compound increases the stability of the TNFα trimer compared to the stability of the TNFα trimer in the absence of the compound;
- c) selecting a compound that increases the stability of the TNFα trimer compared to the stability of the TNFα trimer in the absence of the compound,
- whereby the compound-trimer complex binds to the TNF receptor and modulates the signalling of the receptor.
Dependencies are inferred from the claim text.