Small-molecule pan-IAP antagonists: a patent review

Expert Opinion on Therapeutic Patents
John A Flygare, Wayne J Fairbrother

Abstract

The inhibitor of apoptosis (IAP) proteins are critical regulators of cancer cell survival that have become important targets for therapeutic intervention in human malignancies. One strategy for targeting IAP proteins involves agents that mimic the amino terminus of the endogenous IAP protein antagonist second mitochondria-derived activator of caspases (Smac)/direct IAP-binding protein with low pI (DIABLO) and thus block critical IAP protein interactions. This review of the IAP antagonist patent literature covers the period from 2000 to mid-2009. Over 50 patents and patent applications pertaining to IAP antagonists have been published over the past 10 years. In the case of several filings, only the original source is reviewed in this analysis. Readers will gain an overview of IAP protein antagonist scaffolds, with representative examples including monovalent and bivalent Smac mimetics, and an understanding of their structure-activity relationships. The feasibility of disrupting IAP protein interactions with pro-apoptotic proteins using monovalent and bivalent Smac-derived peptidomimetic compounds has been broadly established. Four such compounds have entered or been approved to enter human clinical trials, which will hopefully a...Continue Reading

References

Aug 1, 1994·Molecular and Cellular Biology·R J Clem, L K Miller
Apr 1, 1993·Journal of Virology·N E CrookL K Miller
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·Z L ChuD W Ballard
May 9, 1998·The Journal of Biological Chemistry·R TakahashiJ C Reed
Apr 21, 1999·Current Opinion in Cell Biology·A Ashkenazi, V M Dixit
Aug 10, 2000·The Journal of Biological Chemistry·C SunS W Fesik
Oct 12, 2000·The Journal of Biological Chemistry·G M Kasof, B C Gomes
Mar 21, 2001·Cell·J ChaiP Dataa
Mar 21, 2001·Cell·S J RiedlG S Salvesen
May 18, 2001·The Journal of Biological Chemistry·S Birkey ReffeyC S Duckett
Jan 22, 2002·The Journal of Biological Chemistry·Domagoj VucicVishva M Dixit
Jan 31, 2002·Current Biology : CB·Srinivasa M SrinivasulaEmad S Alnemri
Feb 28, 2002·Molecular and Cellular Biology·M Germana SannaRichard J Ulevitch
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·Guy S Salvesen, Colin S Duckett
Jun 26, 2002·Carcinogenesis·Gavin J GordonRaphael Bueno
Sep 10, 2002·The Journal of Biological Chemistry·Christina R ArntScott H Kaufmann
Mar 7, 2003·Molecular Cell·Eric N ShiozakiYigong Shi
Nov 25, 2003·Oncogene·Peter ListonRobert G Korneluk
Jun 29, 2004·Seminars in Cancer Biology·Boaz NachmiasDina Ben-Yehuda
Aug 20, 2004·Journal of Medicinal Chemistry·Thorsten K OostStephen W Fesik
Dec 14, 2004·The Biochemical Journal·Colin S Duckett
Apr 2, 2005·Nature Reviews. Molecular Cell Biology·David L Vaux, John Silke

❮ Previous
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Citations

Sep 13, 2011·ACS Combinatorial Science·Sebastian T Le QuementThomas E Nielsen
Apr 15, 2011·Cell Death & Disease·H H CheungR G Korneluk
Feb 2, 2012·Nature Reviews. Drug Discovery·Simone Fulda, Domagoj Vucic
Oct 12, 2010·Oncogene·V PavetH Gronemeyer
Feb 23, 2011·Integrative Biology : Quantitative Biosciences From Nano to Macro·Jessica PlatiRoya Khosravi-Far
Oct 20, 2010·The Journal of Biological Chemistry·Herman H CheungRobert G Korneluk
Jul 31, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Harvey WongWayne J Fairbrother
Sep 8, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Rebecca I EricksonDolores Diaz
Sep 4, 2013·Acta Crystallographica. Section D, Biological Crystallography·Christine LukacsAndreas Kuglstatter
Mar 16, 2013·American Journal of Respiratory Cell and Molecular Biology·Iyabode O AjayiJeffrey C Horowitz
Nov 11, 2014·Nature Structural & Molecular Biology·Aaron H PhillipsWayne J Fairbrother
Jul 28, 2012·Trends in Immunology·Shawn T BeugRobert G Korneluk
Feb 22, 2012·Bioorganic & Medicinal Chemistry Letters·Aldo BianchiPierfausto Seneci
Jan 17, 2012·Ecotoxicology and Environmental Safety·Valentina ZacchinoMichael J Leaver
Jan 24, 2012·Bioorganic & Medicinal Chemistry Letters·Edward J HennessyCharles A Omer
Jun 18, 2011·Bioorganic & Medicinal Chemistry Letters·Marcos González-LópezNicholas D P Cosford
Jan 29, 2011·Cancer Letters·Günter Eisele, Michael Weller
Aug 6, 2010·Cancer Letters·Jasmin N Dynek, Domagoj Vucic
Mar 5, 2016·Cell Communication and Signaling : CCS·Carles Corbi-Verge, Philip M Kim
Dec 5, 2015·Frontiers in Oncology·Martin Holcik
Jan 27, 2015·Proteins·Federica CossuEloise Mastrangelo
Sep 18, 2015·American Journal of Respiratory Cell and Molecular Biology·Shanna L AshleyJeffrey C Horowitz
Oct 3, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Rong HuKun Yao
May 15, 2012·Biochemical Pharmacology·Kuen-Feng ChenAnn-Lii Cheng
May 20, 2015·Expert Opinion on Therapeutic Patents·Alexander W HirdBin Yang
Jul 21, 2015·ACS Medicinal Chemistry Letters·Yong ZhangRobert M Borzilleri
Oct 6, 2012·Bioorganic & Medicinal Chemistry·Leonardo ManzoniPierfausto Seneci
Jul 8, 2014·Pharmaceutical Patent Analyst·James B Jaquith
Jan 29, 2013·Chemistry & Biology·Bainan WuMaurizio Pellecchia
Jun 20, 2014·ACS Medicinal Chemistry Letters·Michael F T KoehlerGuillaume Lessene
Jul 29, 2018·The FEBS Journal·Alessandro CortiFederica Cossu
Sep 18, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Harvey WongWayne J Fairbrother
May 23, 2017·F1000Research·Darren FinlayKristiina Vuori

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