Structure-based discovery of a novel angiotensin-converting enzyme 2 inhibitor.
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Huentelman MJ, Zubcevic J, Hernandez Prada JA, Xiao X, Dimitrov DS, Raizada MK, Ostrov DA
Structure-based discovery of a novel angiotensin-converting enzyme 2 inhibitor.
Hypertension. 2004 Dec;44(6):903-6. doi: 10.1161/01.HYP.0000146120.29648.36. Epub 2004 Oct 18.
- PubMed ID
- 15492138 [ View in PubMed]
- Abstract
Angiotensin-converting enzyme 2 (ACE2) is considered an important therapeutic target for controlling cardiovascular diseases and severe acute respiratory syndrome (SARS) outbreaks. Recently solved high-resolution crystal structures of the apo-bound and inhibitor-bound forms of ACE2 have provided the basis for a novel molecular docking approach in an attempt to identify ACE2 inhibitors and compounds that block SARS coronavirus spike protein-mediated cell fusion. In this study, approximately 140 000 small molecules were screened by in silico molecular docking. In this structure-activity relation study, the molecules with the highest predicted binding scores were identified and assayed for ACE2 enzymatic inhibitory activity and for their ability to inhibit SARS coronavirus spike protein-mediated cell fusion. This approach identified N-(2-aminoethyl)-1 aziridine-ethanamine as a novel ACE2 inhibitor that also is effective in blocking the SARS coronavirus spike protein-mediated cell fusion. Thus, the molecular docking approach resulting in the inhibitory capacity of N-(2-aminoethyl)-1 aziridine-ethanamine provides an attractive small molecule lead compound on which the development of more effective therapeutic agents could be developed to modulate hypertension and for controlling SARS infections.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions N-(2-Aminoethyl)-1-aziridineethanamine Angiotensin-converting enzyme 2 Protein Humans UnknownInhibitorDetails