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Discovery of potent heterodimeric antagonists of inhibitor of apoptosis proteins (IAPs) with sustained antitumor activity.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2015 Feb 12; Vol. 58 (3), pp. 1556-62. Date of Electronic Publication: 2015 Jan 23. - Publication Year :
- 2015
-
Abstract
- The prominent role of IAPs in controlling cell death and their overexpression in a variety of cancers has prompted the development of IAP antagonists as potential antitumor therapies. We describe the identification of a series of heterodimeric antagonists with highly potent antiproliferative activities in cIAP- and XIAP-dependent cell lines. Compounds 15 and 17 further demonstrate curative efficacy in human melanoma and lung cancer xenograft models and are promising candidates for advanced studies.
- Subjects :
- Animals
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Cell Line, Tumor
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Mice
Molecular Structure
Neoplasms, Experimental pathology
Proline chemical synthesis
Proline chemistry
Structure-Activity Relationship
Antineoplastic Agents pharmacology
Drug Discovery
Inhibitor of Apoptosis Proteins antagonists & inhibitors
Neoplasms, Experimental drug therapy
Proline pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 58
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 25584393
- Full Text :
- https://doi.org/10.1021/jm501482t