In vivo efficacy of natural product-inspired irreversible kinase inhibitors

Chembiochem : a European Journal of Chemical Biology
Sofia BarluengaNicolas Winssinger

Abstract

Hypothemycin and related resorcylic acid lactones (RAL) bearing a cis-enone moiety have emerged as an alternative pharmacophore to heterocyclic motifs for kinase inhibition, and are endowed with a unique selectivity filter based on the irreversible reaction with a subset of the kinome bearing a suitably positioned cysteine residue. Two prototypical examples of "edited" RAL were evaluated for antitumoral, antimetastatic and antiangiogenic efficacy in an orthotopic murine renal cell carcinoma (RENCA) model. Both compounds (3 and 5) are good inhibitors of VEGFRs in vitro, and inhibited tumor growth in vivo with comparable efficacy to sunitinib, an FDA-approved VEGFRs inhibitor. Compound 3 promoted lung metastasis to a similar extent as sunitinib, while compound 5 strongly inhibited lung metastasis. This study attests to the potential of irreversible kinase inhibitors and molecular editing of natural pharmacophores and provides encouraging results to a clinically significant problem.

References

Dec 14, 1999·Japanese Journal of Cancer Research : Gann·H TanakaT Yoshioka
Jan 30, 2004·Organic Letters·Xudong Geng, Samuel J Danishefsky
Jun 4, 2004·The New England Journal of Medicine·Herbert HurwitzFairooz Kabbinavar
Sep 2, 2004·Nature Reviews. Drug Discovery·David C Swinney
Feb 16, 2005·Nature Biotechnology·Miles A FabianDavid J Lockhart
Sep 9, 2005·Angewandte Chemie·Carmen DrahlErik J Sorensen
Dec 7, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Robert J MotzerBrian I Rini
Mar 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Andreas SchirmerDaniel V Santi
May 20, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Charles ErlichmanEric K Rowinsky
Aug 5, 2006·Nature Reviews. Drug Discovery·Robert A CopelandThomas D Meek
Aug 16, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ghassan K Abou-AlfaLeonard B Saltz
Oct 27, 2006·The Journal of Organic Chemistry·Rebecca M Wilson, Samuel J Danishefsky
Nov 18, 2006·Cell·Gaorav P Gupta, Joan Massagué
Jan 12, 2007·The New England Journal of Medicine·Bernard EscudierUNKNOWN TARGET Study Group
Feb 7, 2007·Chemical Communications : Chem Comm·Nicolas Winssinger, Sofia Barluenga
Mar 31, 2007·Nature Reviews. Drug Discovery·Judah Folkman
Aug 7, 2007·Angewandte Chemie·Pierre-Yves DakasNicolas Winssinger
Sep 1, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Pasi A JännePhilip D Bonomi
Dec 28, 2007·The New England Journal of Medicine·Kathy MillerNancy E Davidson
Jan 10, 2008·Nature Biotechnology·Mazen W KaramanPatrick P Zarrinkar
May 9, 2008·The New England Journal of Medicine·Robert S Kerbel
Jun 24, 2008·Journal of Structural Biology·Giulio RastelliDaniel V Santi
Jul 25, 2008·Nature Reviews. Cancer·Gabriele Bergers, Douglas Hanahan
Nov 26, 2008·Bioorganic & Medicinal Chemistry·K C NicolaouStephen M Dalby
Dec 24, 2008·Nature Reviews. Cancer·Jianming ZhangNathanael S Gray
Feb 11, 2009·Journal of Medicinal Chemistry·Michele H Potashman, Mark E Duggan
Sep 29, 2009·Bioorganic & Medicinal Chemistry Letters·H DuY Wang
Mar 9, 2010·ChemMedChem·Rajamalleswaramma JogireddyNicolas Winssinger

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Citations

May 25, 2012·Journal of Medicinal Chemistry·Tjeerd Barf, Allard Kaptein
Jan 15, 2015·Future Medicinal Chemistry·Iain Kilty, Lyn H Jones
Jan 14, 2011·Natural Product Reports·Mostafa E Rateb, Rainer Ebel
Oct 29, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ian Collins, Alan M Jones
Sep 17, 2014·Chembiochem : a European Journal of Chemical Biology·Ashwini K DevkotaKevin N Dalby
Feb 27, 2013·Chemistry & Biology·Qingsong LiuNathanael S Gray
Dec 3, 2014·Bioorganic & Medicinal Chemistry·Jin XuChristina L L Chai
Aug 14, 2012·Biochemical Pharmacology·Caterina CarmiRoberta R Alfieri
Oct 11, 2017·Angewandte Chemie·Apirat ChaikuadStefan Knapp
Nov 2, 2017·The Journal of Antibiotics·Roman LagoutteNicolas Winssinger
Apr 22, 2020·Future Medicinal Chemistry·Lexian TongTao Liu
Apr 1, 2020·Chemical Society Reviews·Ayah AbdeldayemPatrick T Gunning
Jun 14, 2017·Current Opinion in Chemical Biology·Roman LagoutteNicolas Winssinger

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