Löhn M, Plettenburg O, Kannt A, Kohlmann M, Hofmeister A, Kadereit D, Monecke P, Schiffer A, Schulte A, Ruetten H, Ivashchenko Y. End-organ protection in hypertension by the novel and selective Rho-kinase inhibitor, SAR407899. World J Cardiol 2015; 7(1): 31-42 [PMID: 25632317 DOI: 10.4330/wjc.v7.i1.31]
Corresponding Author of This Article
Dr. Matthias Löhn, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany. matthias.loehn@sanofi.com
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Case Control Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Cardiol. Jan 26, 2015; 7(1): 31-42 Published online Jan 26, 2015. doi: 10.4330/wjc.v7.i1.31
End-organ protection in hypertension by the novel and selective Rho-kinase inhibitor, SAR407899
Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko
Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany
Author contributions: Löhn M performed the majority of experiments, designed the study and wrote the manuscript; Plettenburg O, Hofmeister A and Kadereit D designed and synthetized SAR407899; Kannt A performed an initial compound screening; Kohlmann M performed the pharmacokinetics of SAR407899; Monecke P and Schiffer A were involved in structural biology and modeling required for the compound optimization; Schulte A performed the histology; Ruetten H and Ivashchenko Y were also involved in writing and editing the manuscript.
Ethics approval: All animal experiments were performed in accordance with the German law for the protection of animals and current Aventis Laboratory Animal Science and Welfare (LASW) guidelines.
Informed consent: Not applicable.
Conflict-of-interest: There is no conflict-of-interest to disclose. All authors are employees of Sanofi-Aventis Deutschland GmbH.
Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at Matthias.loehn@sanofi.com. Participants gave informed consent for data sharing. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Matthias Löhn, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany. matthias.loehn@sanofi.com
Telephone: +49-69-30517118
Received: July 14, 2014 Peer-review started: July 15, 2014 First decision: November 3, 2014 Revised: December 12, 2014 Accepted: December 29, 2014 Article in press: January 4, 2015 Published online: January 26, 2015
Core Tip
Core tip: Rho-kinase (ROCK) is considered an important target in cardiovascular diseases, e.g., hypertension and nephropathy. Currently available treatment only moderately alleviates the progression of chronic kidney diseases. We have identified a novel, potent and selective inhibitor of ROCK (SAR407899) and characterized its effects in vivo. The therapeutic efficacy of SAR407899 has been compared to the current standard treatment for hypertension in two animal models of hypertension, one of which is sensitive and the other insensitive (deoxycorticosterone acetate) to angiotensin converting enzyme-inhibition. ROCK-inhibition by SAR407899 may represent a new therapeutic option either as a monotherapy or in combination with existing modern therapeutics for the treatment of hypertension and its complications.
