The present invention relates to a method for identifying compounds capable of modulating the function of a functional domain of human HIF-1.alpha., said method comprising (i) contacting a candidate compound with a variant of huma n HIF-1.alpha., said variant essentially lacking at least one functional domai n of human HIF-1.alpha., or having a mutation making at least one functional domain of human HIF-1.alpha. essentially inactive, said functional domain or domains being selected from the group consisting of (a) the PAS-B domain located in human HIF-1.alpha. between amino acids 178 and 390, (b) the C- terminal nuclear localization sequence (NLS) located in human HIF-1.alpha. essentially at amino acids 718 to 721, and (c) the transactivator / coactivator domain (N-TAD) located in human HIF-1.alpha. essentially between amino acids 531 to 584, and (d) the transactivator / coactivator domain (C- TAD) located in human HIF-1.alpha. essentially between amino acids 813 and 826, and (ii) determining the effect of the candidate compound on the said variant.
HYPOXIA-INDUCIBLE FACTOR 1.ALPHA. HIF-1.ALPHA. VARIANTS AND METHODS FOR IDENTIFYING HIF-1.ALPHA. MODULATORS