Method for screening compounds inhibiting signal transduction through inflammatory cytokines
AssigneeChugai Seiyaku Kabushiki Kaisha
InventorsMasayuki Tsuchiya, Toshihiko Ohtomo, Yasuhiro Sugamata, Kunihiro Matsumoto
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Abstract
Revealed are that the actions of inflammatory cytokine and the production of inflammatory cytokines such as IL-1 and TNF induced by an inflammatory stimulus as well as the production of other inflammatory cytokines such as IL-6 induced by the former class of inflammatory cytokines are all suppressed by inhibiting the signal transduction through TAK1.
Claims42
1-40. (canceled)
A method of screening for compounds that inhibit production of an inflammatory cytokine, comprising:
- (a) providing a sample comprising a TAK1 and a TAB1;
- (b) contacting a test compound with the TAK1 and the TAB 1;
- (c) detecting binding between the TAK1 and the TAB 1;
- and
- (d) selecting a compound that inhibits the binding;
- wherein the TAK1 of (a) is selected from the group consisting of
- (i) a protein comprising amino acids 76 to 303 of SEQ ID NO:2;
- and
- (ii) a protein that binds to amino acids 437 to 504 of SEQ ID NO:4 and comprises an amino acid sequence encoded by a DNA sequence that hybridizes with the complement of nucleotides 408 to 1091 of SEQ ID NO:
- 1 under washing conditions of 42° C., 5×SSC, 0.1% sodium dodecyl sulfate, and 50% formamide;
- and wherein the TAB 1 of (a) is selected from the group consisting of
- (iii) a protein comprising amino acids 437 to 504 of SEQ ID NO:4;
- and
- (iv) a protein that binds to amino acids 76 to 303 of SEQ ID NO:2 and comprises an amino acid sequence encoded by a DNA that hybridizes with the complement of nucleotides 1338 to 1541 of SEQ ID NO:3 under washing conditions of 42° C., 5×SSC, 0.1% sodium dodecyl sulfate, and 50% formamide;
- wherein the compound inhibits production of an inflammatory cytokine produced in response to binding between TAK1 and TAB 1.
A method of screening for compounds that inhibit production of an inflammatory cytokine, comprising:
- (a) providing a sample comprising a TAK1 and a TAB1;
- (b) contacting a test compound with the TAK1 and the TAB1;
- (c) detecting binding between the TAK1 and the TAB1;
- and
- (d) selecting a compound that inhibits the binding;
- wherein the TAK1 of (a) is selected from the group consisting of
- (i) a protein comprising amino acids 76 to 303 of SEQ ID NO:2;
- and
- (ii) a protein that binds to amino acids 437 to 504 of SEQ ID NO:4 and comprises an amino acid sequence encoded by a DNA sequence that hybridizes with the complement of nucleotides 408 to 1091 of SEQ ID NO:1 under washing conditions of 42° C., 5×SSC, 0.1% sodium dodecyl sulfate, and 50% formamide;
- and wherein the TAB 1 of (a) is selected from the group consisting of
- (iii) a protein comprising amino acids 437 to 504 of SEQ ID NO:4;
- and
- (iv) a protein that binds to amino acids 76 to 303 of SEQ ID NO:2 and comprises an amino acid sequence encoded by a DNA that hybridizes with the complement of nucleotides 1338 to 1541 of SEQ ID NO:3 under washing conditions of 42° C., 5×SSC, 0.1% sodium dodecyl sulfate, and 50% formamide;
- wherein the compound inhibits production of an inflammatory cytokine produced in response to IL-1, TNF or IL-6.
Dependencies are inferred from the claim text.