Methods and compositions for derepression of IAP-inhibited caspase

US6911426B2 · kind B2 · utility

Assignees

• The Burnham Institute · US
• Torrey Pines Institute for Molecular Studies · US

Inventors

• John C. Reed · Rancho Santa Fe, US
• Richard A. Houghten · Del Mar, US
• Adel Nefzi · San Diego, US
• John M. Ostresh · Encinitas, US
• Clemencia Pinilla · Port St. Lucie, US
• Kate Welsh · San Diego, US

Key dates

• Filing date: Nov 21, 2002
• Grant date: Jun 28, 2005
• Expiry date: Dec 17, 2022

Classification

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

Abstract

The invention provides isolated agents having a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through 55, wherein the agent derepresses an IAP-inhibited caspase. Also provided is an isolated agent having a core structure selected from any of the structures shown in FIGS. 5, 9, 10, 14B, and 21-24 wherein said agent derepresses an IAP-inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The method consists of contacting an IAP-inhibited caspase with an effective amount of an agent to derepress an IAP-inhibited caspase, the agent having a core motif selected from the group consisting of a core peptide having a sequence set forth in any of Core peptides 4 through 39 and 42 through 55, and a core structure selected from the group consisting of TPI759, TPI882, TPI914 or TPI927. The methods of the invention also can be used for promoting apoptosis in a cell and for reducing the severity of a pathology characterized by reduced levels of apoptosis. Methods for identifying agents that derepress an IAP-inhibited caspase are also provided.