Virtual Screening for FDA-Approved Drugs That Selectively Inhibit Arginase Type 1 and 2

Trishna Saha Detroja, Abraham O. Samson

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Arginases are often overexpressed in human diseases, and they are an important target for developing anti-aging and antineoplastic drugs. Arginase type 1 (ARG1) is a cytosolic enzyme, and arginase type 2 (ARG2) is a mitochondrial one. In this study, a dataset containing 2115-FDA-approved drug molecules is virtually screened for potential arginase binding using molecular docking against several ARG1 and ARG2 structures. The potential arginase ligands are classified into three categories: (1) Non-selective, (2) ARG1 selective, and (3) ARG2 selective. The evaluated potential arginase ligands are then compared with their clinical use. Remarkably, half of the top 30 potential drugs are used clinically to lower blood pressure and treat cancer, infection, kidney disease, and Parkinson’s disease thus partially validating our virtual screen. Most notable are the antihypertensive drugs candesartan, irbesartan, indapamide, and amiloride, the antiemetic rolapitant, the anti-angina ivabradine, and the antidiabetic metformin which have minimal side effects. The partial validation also favors the idea that the other half of the top 30 potential drugs could be used in therapeutic settings. The three categories greatly expand the selectivity of arginase inhibition.

Original languageEnglish
Article number5134
JournalMolecules
Volume27
Issue number16
DOIs
StatePublished - 12 Aug 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors.

Keywords

  • ARG1
  • ARG2
  • FDA
  • arginase
  • molecular docking
  • vina
  • virtual screening

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