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Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
Small-molecule pan-IAP antagonists: a patent review
John A Flygare1, Wayne J Fairbrother
1Genentech, Inc., Department of Medicinal Chemistry, 1 DNA Way, South San Francisco, CA 94080, USA.
Expert Opinion on Therapeutic Patents
|January 27, 2010
Summary
Inhibitor of apoptosis (IAP) protein antagonists, including Smac mimetics, are crucial for cancer therapy. These compounds disrupt IAP interactions, with several now in clinical trials for cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Inhibitor of apoptosis (IAP) proteins are key regulators of cancer cell survival.
- Targeting IAP proteins is a significant therapeutic strategy in oncology.
- Agents mimicking the second mitochondria-derived activator of caspases (Smac)/DIABLO protein can block IAP interactions.
Purpose of the Study:
- To review the patent literature on IAP antagonists from 2000 to mid-2009.
- To provide an overview of IAP antagonist scaffolds and their structure-activity relationships.
- To highlight the development of Smac mimetic compounds.
Main Methods:
- Comprehensive review of over 50 patents and patent applications related to IAP antagonists.
- Analysis focused on the period from 2000 to mid-2009.
- Examination of monovalent and bivalent Smac mimetic scaffolds.
Main Results:
- Identification of various IAP protein antagonist scaffolds, including monovalent and bivalent Smac mimetics.
- Understanding of structure-activity relationships for these IAP antagonists.
- Overview of the patent landscape for IAP-targeting agents.
Conclusions:
- The disruption of IAP protein interactions using Smac-derived peptidomimetics is feasible.
- Monovalent and bivalent Smac mimetics represent promising therapeutic approaches.
- Four Smac mimetic compounds have advanced to human clinical trials for cancer treatment evaluation.
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