Modulation of epidermal growth factor heterodimer activity
First Claim
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1. A method for screening a plurality of compounds for an ability to bind to a heterodimer of EGFR and another ERBB family member, the method comprising:
- (a) contacting a first structure comprising an EGFR/ERBB heterodimer with a first solution, the first solution comprising the plurality of compounds;
(b) removing any compounds bound to the first structure to produce a second solution;
(c) contacting a second structure comprising an EGFR homodimer with the second solution, wherein the first structure and the second structure are identical except that the second structure does not contain an ERBB family member other than EGFR; and
(d) recovering any unbound compounds to produce a third solution,whereby a compound that binds to a heterodimer of EGFR and another ERBB family member is identified.
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Abstract
Provided is a method for screening a plurality of compounds for an ability to bind to a heterodimer of EGFR and another ERBB family member. Also provided are compounds that bind to heterodimers of EGFR and another ERBB family member; and methods of using the identified compounds to suppress the growth of a tumor associated with EGFR heterodimer activity in a subject.
3 Citations
28 Claims
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1. A method for screening a plurality of compounds for an ability to bind to a heterodimer of EGFR and another ERBB family member, the method comprising:
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(a) contacting a first structure comprising an EGFR/ERBB heterodimer with a first solution, the first solution comprising the plurality of compounds; (b) removing any compounds bound to the first structure to produce a second solution; (c) contacting a second structure comprising an EGFR homodimer with the second solution, wherein the first structure and the second structure are identical except that the second structure does not contain an ERBB family member other than EGFR; and (d) recovering any unbound compounds to produce a third solution, whereby a compound that binds to a heterodimer of EGFR and another ERBB family member is identified. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
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20. A method for identifying an antibody that specifically binds to an EGFR heterodimer, the method comprising:
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(a) isolating a membrane fraction of a cell, wherein the membrane fraction of the cell comprises EGFR and at least one of ERBB2, ERBB3, and ERBB4; (b) immunizing a mammalian subject with the membrane fraction; and (c) purifying an antibody from the antisera that specifically binds to an EGFR heterodimer. - View Dependent Claims (21, 22)
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23. A method for identifying a compound that inhibits formation of a heterodimer between EGFR and another ERBB family member, the method comprising:
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(a) producing a first solution comprising a plurality of molecules that bind to EGFR; (b) producing a second solution comprising a plurality of molecules that bind to the other ERBB family member; (c) contacting the first solution with a first structure comprising a plurality of EGFR homodimers under conditions sufficient to allow any of the plurality of molecules to bind to the EGFR homodimers; (d) contacting the second solution with a second structure comprising a plurality of homodimers of the other ERBB family member under conditions sufficient to allow any of the plurality of molecules to bind to the homodimers of the other ERBB family member; (e) pooling any unbound compounds from the first and second solutions to produce a third solution; and (f) testing the unbound compounds in the third solution for an ability to inhibit formation of a heterodimer between EGFR and the other ERBB family member, whereby a compound that inhibits formation of a heterodimer between EGFR and the other ERBB family member is identified. - View Dependent Claims (24, 25, 26, 27, 28)
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Specification