Methods for identifying compounds that antagonize cd40 signaling
OwnerJonathan M.J. Derry, William C. Fanslow III +1inventors
InventorsJonathan M.J. Derry, William C. Fanslow III, William C. Dougall
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Abstract
The present invention provides methods for identifying a molecule that antagonizes or agonizes CD40 activity by screening for molecules that modulate the binding of NEMO and CYLD. Also provided are assays useful in screening for the binding of NEMO and CYLD and databases and methods useful for analyzing the resultant information.
Claims24
A method for identifying compounds that alter one or more biological activities of CD40, comprising:
- (a) mixing a test compound with a polypeptide selected from the group consisting of (i) a NEMO polypeptide comprising amino acids 287 through 419 SEQ ID NO:2, (ii) a fragment of a NEMO polypeptide according to (i) that is capable of binding a CYLD polypeptide according to SEQ ID NO:4 or fragment or variant thereof, and (iii) variants of the NEMO polypeptides of (i) and (ii);
- and
- (b) determining whether the test compound alters the ability of NEMO to bind CYLD.
A method for identifying compounds that inhibit binding of NEMO and CYLD comprising:
- (a) mixing a test compound with a polypeptide selected from the group consisting of (i) a NEMO polypeptide comprising amino acids 287 through 419 SEQ ID NO:2, (ii) a fragment of a NEMO polypeptide according to (i) that is capable of binding a CYLD polypeptide according to SEQ ID NO:4, and (iii) variants of the NEMO polypeptides of (i) and (ii), and a binding partner of said NEMO polypeptide selected from the group consisting of (iv) a CYLD polypeptide according to SEQ ID NO:4, (v) a fragment of a CYLD polypeptide according to SEQ ID NO:4 that is capable of binding a NEMO polypeptide of (i), (ii), or (iii), and (vi) a variant of the CYLD polypeptides of (iv) and (v) that is capable of binding a NEMO polypeptide of (i), (ii), or (iii);
- and
- (b) determining whether the test compound inhibits the binding activity of said NEMO and CYLD polypeptides.
A method for producing information comprising the identity of a compound that alters one or more biological activities of CD40, the method comprising identifying one or more compounds that alter NEMO/CYLD binding activity.
A computer system for storing and retrieving data on a plurality of compounds, the computer system comprising:
- (a) input means for entering data for the compounds into a storage medium;
- a processor for creating an individual record for each compound, the processor assigning specific identifying values for each compound;
- (b) means for selecting one or more of the records based on results in an assay;
- and
- (c) means for transmitting information in the record or records to an output device to produce a report.
A method of operating a computer system for analyzing compounds that modulate the interaction of NEMO and CYLD, the method comprising:
- (a) entering data relating to a plurality of compounds into a storage medium;
- processing the data to create an individual record for each compound;
- (b) testing compounds for the ability to modulate binding of NEMO to CYLD;
- and
- (c) communicating results from the testing into the storage medium such that results for each compound are associated with the individual record for that compound.
Dependencies are inferred from the claim text.