PMID: 16614731Apr 15, 2006Paper

CGS 35601, a triple inhibitor of angiotensin converting enzyme, neutral endopeptidase and endothelin converting enzyme

Cardiovascular Drug Reviews
Bruno BattistiniArco Y Jeng

Abstract

CGS 35601 (L-tryptophan, N-[[1-[[(2S)-2-mercapto-4-methyl-1-oxopentyl]amino]-cyclopentyl]carbonyl]) is one of a few single molecules capable of inhibiting the activities of angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP) and endothelin converting enzyme (ECE) simultaneously, with IC(50) values of 22, 2, and 55 nM, respectively. Through the inhibition of ACE and ECE, it blocks the conversion of angiotensin I (AI) and big endothelin-1 (big ET-1) into the two most potent peptidic vasoconstrictors, angiotensin II (AII) and ET-1, respectively. By inhibiting NEP, CGS 35601 also prevents the degradation of peptidic vasodilators such as bradykinin (BK), natriuretic peptides (NPs) and adrenomedullin (ADM) and, hence, modulates the secondary release of other vasoactive mediators such as nitric oxide (NO) and prostaglandins. In chronic (30 days) experiments, CGS 35601 is well tolerated with a very good safety profile in healthy normotensive, hypertensive and type 2 diabetic rats. The antihypertensive efficacy of CGS 35601 was demonstrated in chronically instrumented, unrestrained and conscious rat models of hypertension (SHR and DSS) and type 2 diabetes (ZDF-fatty). It lowered blood pressure effectively as well as modulat...Continue Reading

References

May 1, 1990·Diabetologia·K TakahashiS R Bloom
Apr 1, 1996·Clinical and Experimental Pharmacology & Physiology·K SugimotoM Ishii
Apr 17, 1998·American Journal of Hypertension·N C TrippodoT R Schaeffer
Jul 28, 1999·Clinical and Experimental Hypertension : CHE·S YusufH Gerstein
Sep 15, 2000·Bioorganic & Medicinal Chemistry Letters·C A FinkA Y Jeng
Dec 21, 2000·Trends in Pharmacological Sciences·B P Roques
Nov 6, 2001·The American Journal of Cardiology·V J DzauUNKNOWN Working Group on Tissue Angiotensin-converting enzyme, International Society of Cardiovascular Pharmacotherapy
Feb 28, 2002·American Journal of Hypertension·John B KostisUNKNOWN OPERA Study Group. Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events
Sep 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Giuseppe MolinaroAlbert Adam
Dec 11, 2002·American Journal of Physiology. Renal Physiology·Kazuaki MoridairaSaulo Klahr
Jul 8, 2003·Current Hypertension Reports·Anne ZanchiMichel Burnier
Feb 18, 2004·Journal of Cardiac Failure·Jiang XuXiao-Ping Yang
Mar 11, 2004·The Journal of Peptide Research : Official Journal of the American Peptide Society·N InguimbertB-P Roques
Sep 10, 2004·The Journal of Allergy and Clinical Immunology·Tom BowenJean de Serres
Nov 3, 2004·British Journal of Pharmacology·João B CalixtoMaria M Campos
Nov 17, 2004·Current Pharmaceutical Design·Lesley WassefDarren J Kelly
Apr 21, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Inka LiesmaaKen A Lindstedt
Aug 24, 2005·Journal of Cardiovascular Pharmacology·Virginie MellinPaul Mulder

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Citations

Dec 1, 2008·Expert Opinion on Drug Discovery·Vincenzo Calderone
Oct 2, 2007·Vascular Pharmacology·Stephanie W WattsGregory D Fink
Sep 20, 2007·Journal of Cardiovascular Pharmacology·Philippe DaullBruno Battistini
Mar 28, 2008·Brain Pathology·James Scott MinersSeth Love
Jun 15, 2007·Physiology·Misuk KangJeffery W Walker
May 4, 2011·Virchows Archiv : an International Journal of Pathology·Achim FleischmannGeorge N Thalmann
Nov 30, 2011·Journal of Neurochemistry·Natalia N NalivaevaAnthony J Turner
Nov 30, 2011·Current Opinion in Nephrology and Hypertension·Karin A M Jandeleit-Dahm, Anna M D Watson
Mar 11, 2020·Clinica Chimica Acta; International Journal of Clinical Chemistry·Eray ErogluBengt Lindholm
May 1, 2010·Biochimie·Neil D Rawlings
Jul 6, 2010·Peptides·Ricardo Fernández-MusolesJuan B Salom

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