Cathepsin A Inhibitors to Treat Heart Disease
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Phase I clinical studies of the CTSA inhibitor SAR164653 in healthy individuals showed a promising safety profile and supported proposed studies for ischaemic cardiomyopathy.
“Phase I clinical studies of the CTSA inhibitor SAR164653 in healthy individuals showed a promising safety profile and supported proposed studies for ischaemic cardiomyopathy 35,36 .”
From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [35]
In “Cathepsin A Inhibitors to Treat Heart Disease” (page not provided), the author reports a phase I trial in 45 healthy subjects with no adverse effects over 14 days, supporting a promising short-term safety profile. The paper does not say that this trial supported proposed studies for ischaemic cardiomyopathy; it calls SAR164653’s clinical trajectory unclear and stresses the need for long-term safety studies. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSAR164653 (CTSAi) is a selective small-molecule inhibitor of CTSA.
“We next evaluated the effect of CTSA inhibition using the selective small-molecule inhibitor SAR164653 (CTSAi) 35,36 .”
From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [35]
The main text (page not provided) identifies SAR164653 as a cathepsin A inhibitor and gives its chemical name, supporting its description as a small-molecule inhibitor. It does not state or establish that SAR164653 is selective, so that qualifier is unsupported by our copy. (LLM, conf=0.84)
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Cites
Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL)
Bugiani, M., Kevelam, S. H., Bakels, H. S., Waisfisz, Q., Ceuterick-de Groote, C., Niessen, H. W. M., Abbink, T. E. M., Lesnik Oberstein, S. A. M. J., & van der Knaap, M. S. (2016) · Neurology · doi:10.1212/wnl.0000000000003251 · Cited by 111 · see citing works
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Research works printed but not linked: 10
- [1]Hiraiwa M. Cathepsin A/protective protein: an unusual lysosomal multifunctional protein Cell Mol Life Sci 56 1999 894 907 11212324 PMC11146757 Hiraiwa M. Cathepsin A/protective protein: an unusual lysosomal multifunctional protein. Cell Mol Life Sci 1999;56:894-907. PMC11146757 11212324
- [2]Seyrantepe V. Hinek A. Peng J. Enzymatic activity of lysosomal carboxypeptidase (cathepsin) A is required for proper elastic fiber formation and inactivation of endothelin-1 Circulation 117 2008 1973 1981 18391110 Seyrantepe V, Hinek A, Peng J. et al. Enzymatic activity of lysosomal carboxypeptidase (cathepsin) A is required for proper elastic fiber formation and inactivation of endothelin-1. Circulation 2008;117:1973-1981. 18391110
- [3]Ruf S. Buning C. Schreuder H. Novel beta-amino acid derivatives as inhibitors of cathepsin A J Med Chem 55 2012 7636 7649 22861813 Ruf S, Buning C, Schreuder H, et al. Novel beta-amino acid derivatives as inhibitors of cathepsin A. J Med Chem 2012;55:7636-7649. 22861813
- [4]Hohl M. Erb K. Lang L. Cathepsin A mediates ventricular remote remodeling and atrial cardiomyopathy in rats with ventricular ischemia/reperfusion J Am Coll Cardiol Basic Trans Science 4 2019 332 344 PMC6609908 31312757 Hohl M, Erb K, Lang L, et al. Cathepsin A mediates ventricular remote remodeling and atrial cardiomyopathy in rats with ventricular ischemia/reperfusion. J Am Coll Cardiol Basic Trans Science 2019;XX:xxx-xx. PMC6609908 31312757
- [5]Linz D. Hohl M. Dhein S. Cathepsin A mediates susceptibility to atrial tachyarrhythmia and impairment of atrial emptying function in Zucker diabetic fatty rats Cardiovasc Res 110 2016 371 380 27032673 Linz D, Hohl M, Dhein S, et al. Cathepsin A mediates susceptibility to atrial tachyarrhythmia and impairment of atrial emptying function in Zucker diabetic fatty rats. Cardiovasc Res 2016;110:371-380. 27032673
- [6]Petrera A. Gassenhuber J. Ruf S. Cathepsin A inhibition attenuates myocardial infarction-induced heart failure on the functional and proteomic levels J Transl Med 14 2016 153 27246731 PMC4888645 Petrera A, Gassenhuber J, Ruf S, et al. Cathepsin A inhibition attenuates myocardial infarction-induced heart failure on the functional and proteomic levels. J Transl Med 2016;14:153. PMC4888645 27246731
- [7]Zolk O. Bohm M. The role of the cardiac endothelin system in heart failure Nephrol Dial Transplant 15 2000 758 760 10831623 Zolk O, Bohm M. The role of the cardiac endothelin system in heart failure. Nephrol Dial Transplant 2000;15:758-760. 10831623
- [10]Tillner J. Lehmann A. Paehler T. Tolerability, safety, and pharmacokinetics of the novel cathepsin A inhibitor SAR164653 in healthy subjects Clin Pharmacol Drug Dev 5 2016 57 68 27119579 Tillner J, Lehmann A, Paehler T, et al. Tolerability, safety, and pharmacokinetics of the novel cathepsin A inhibitor SAR164653 in healthy subjects. Clin Pharmacol Drug Dev 2016;5:57-68. 27119579
- [11]McMurray J.J. Packer M. Desai A.S. Angiotensin-neprilysin inhibition versus enalapril in heart failure N Engl J Med 371 2014 993 1004 25176015 McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004. 25176015
- [12]Braunwald E. The path to an angiotensin receptor antagonist-neprilysin inhibitor in the treatment of heart failure J Am Coll Cardiol 65 2015 1029 1041 25766951 Braunwald E. The path to an angiotensin receptor antagonist-neprilysin inhibitor in the treatment of heart failure. J Am Coll Cardiol 2015;65:1029-1041. 25766951
Cited by
Sorted by citations
Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover
Feng, X., Zhang, S., Wang, Y., Kurlagunda, T., Sit, A., Jaishankar, P., Yang, P., Sakane, S., Park, S. Y., Wisessaowapak, C., et al. (2026) · Nature · doi:10.1038/s41586-026-10697-z · Cited by 2 · see citing works
- Authors
- Cowling, R. T.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Cowling, Randy T.
- ORCID
- Cowling, Randy T.
- Venue
- JACC: Basic to Translational Science
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 4
- Issue
- 3
- Pages
- 345-347
- ISSN
- 2452-302X (ISSN-L)
- PMC
- PMC6610153
- OpenAlex
- W2955787986
- Cited by
- 8
- References
- 1
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2020: 2
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- JACC Basic to Translational Science (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL141361)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- cathepsin A, heart disease, protease inhibition
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