Method of identifying compounds that modulate the function of the human hypoxia-inducible factor 1-alpha (HIF-1alpha) functional domain

摘要

Described is a method for identifying compounds capable of modulating the function of a functional domain of human HIF-1 alpha; the method comprising (i) contacting a candidate compound with a variant of human HIF-1 alpha, the variant essentially lacking at least one functional domain of human HIF-1 alpha, or having a mutation making at least one functional domain of human HIF-1 alpha essentially inactive. The 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 localisation sequence (NLS) located in human HIF-1 alpha at amino acids 718 to 721, and (c) the transactivator/coactivator domain (N-TAD) located in human HIF-1 alpha between amino acids 531 to 584, and (d) the transactivator/coactivator domain (C-TAD) located in human HIF-1 alpha between amino acids 813 and 826, and (ii) determining the effect of the candidate compound on the variant.