Patent ID: 8489339

Claim:
A method of drug selection comprising, a) obtaining a crystal belonging to the space group P6 3 22 with unit cell dimensions a=b=166.6 Å and c=213.1 Å, the crystal consisting of the polypeptide complex of GM-CSF of SEQ ID NO:16, soluble GM-CSFRα of SEQ ID NO:17 and soluble βc N346Q of SEQ ID NO:18; b) determining the three-dimensional structure of the complex by the X-ray diffraction method to obtain the atomic coordinates in Table 1; c) screening the atomic coordinates of Table 1 against a database of chemical entities to identify a chemical entity putatively able to associate with an interactive surface between granulocyte macrophage-colony stimulating factor (GM-CSF), GM-CSF receptor subunit alpha (GM-CSFRα) and GM-CSF receptor subunit beta-c (βc), wherein the interactive surface is selected from the group consisting of: (i) a site on GM-CSF defined by amino acid residues 11 to 23 and 112 to 118 of SEQ ID No. 16, (ii) a site on GM-CSFRα selected from: (a) amino acid residues 241 to 251 and 299 to 305 of SEQ ID No. 17, (b) amino acid residues 231, 232, 259, 266 to 270 and 280 to 286 of SEQ ID No. 17, and (c) amino acid residues 260 and 261 of SEQ ID No. 17, (iii) a site on βc selected from: (a) amino acid residues 106 to 113, 360 to 369 and 417 to 423 of SEQ ID No. 18, (b) amino acid residues 346 to 354, 357, 359, 362 and 430 to 435 of SEQ ID No. 18, and (c) amino acid residues 350, 353, 366 to 369, 389 to 400, and 418 of SEQ ID No. 18, d) selecting a chemical entity which computationally associates with the interactive surface for testing in a GM-CSF activity assay, e) incorporating said selected chemical entity into a biological cytokine activity assay; and f) determining whether said chemical entity inhibits the biological activity of human GM-CSF-mediated signaling.