Methods for identifying compounds that modulate HIF-1&agr;

US6436654B1 · kind B1 · utility

Assignee

• Pharmacia & UpJohn AB · SE

Inventors

• Anders Berkenstam · Stockholm, SE
• Lorenz Poellinger · Stockholm, SE

Key dates

• Filing date: Nov 12, 1999
• Grant date: Aug 20, 2002
• Expiry date: Nov 12, 2019

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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