Patent ID: 6436654
Filing Date: 2002-08-20
Classification: A61K,C07K

Abstract:
A method for identifying compounds which modulate the function of a functional domain of human HIF-1&agr; having the sequence SEQ ID NO:1, said method comprising:(i) contacting a candidate compound with a modified human HIF-1&agr;, said modified human HIF-1&agr; lacking at least one functional domain of native human HIF-1&agr;, or having at least one functional domain of native human HIF-1&agr; which is inactive, said functional domain or domains being selected from the group consisting of (a) the PAS-B domain located in sequence SEQ ID NO:1 between amino acids 178 and 390, (b) the C-terminal nuclear localization sequence located in sequence SEQ ID NO:1 from amino acids 718 to 721, (c) the transactivator domain located in sequence SEQ ID NO:1 between amino acids 531 to 584, and (d) the transactivator domain located in sequence SEQ ID NO:1 between amino acids 813 and 826, and (ii) determining the effect of the candidate compound on the modified human HIF-1&agr;; wherein the method is carried out in the presence of a transcriptional coactivator selected from the group consisting of SRC-1, TIF2 and mixtures thereof.