Affinity of Nintedanib Towards New Candidate Target for Idiopathic Pulmonary Fibrosis

Hari Baskar Balasubramanian (1) , Sima Biswas (2) , Maria Talmon (3) , Filippo Patrucco (4) , Piero Emilio Balbo (5) , Luigia Grazia Fresu (6) , Angshuman Bagchi (7)
(1) Università degli Studi del Piemonte Orientale “Amedeo Avogadro” , Italy
(2) University of Kalyani , India
(3) Università degli Studi del Piemonte Orientale “Amedeo Avogadro” , Italy
(4) Università degli Studi del Piemonte Orientale “Amedeo Avogadro” , Italy
(5) Azienda Ospedaliero Universitaria Maggiore della Carita , Italy
(6) Università degli Studi del Piemonte Orientale “Amedeo Avogadro” , Italy
(7) University of Kalyani , India

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive disease due to aggregation of fibroblasts on lung parenchyma. Nintedanib, an indolinone-derived tyrosine kinase inhibitor (TKi) has been approved for the treatment of IPF and it is a well-known inhibitor of platelet-derived growth factor (PDGF) receptor-α and -β, fibroblast growth factor (FGF) receptor-1–3 and vascular endothelial growth factor (VEGF) receptor-1–3. This study aims to evaluate the binding interaction between new therapeutic protein candidates for IPF such as autotaxin, galectin-3, interleukin-13, chitotriosidase-1, JNK, RhoE-ROCK-1, ROCK-2 against nintedanib. In this investigation we predicted, computed, and analyzed the binding interactions of the drug nintedanib using an in silico approach called molecular docking. Our docking studies demonstrated that RhoE-ROCK1 and autotaxin showed strong binding affinities towards nintedanib compared to known targets such as VEGFR2 and FGFR1. We can therefore hypothesize a further contribution of nintedanib to the improvement of pathology due to its affinity towards new targets in the pathogenesis of IPF. The next step will be to evaluate the effects of this affinity in vitro on specific cellular models.

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Authors

Hari Baskar Balasubramanian
Sima Biswas
Maria Talmon
Filippo Patrucco
Piero Emilio Balbo
Luigia Grazia Fresu
luigia.fresu@med.uniupo.it (Primary Contact)
Angshuman Bagchi
Author Biographies

Hari Baskar Balasubramanian, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”

Department of Health Sciences, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, Novara, Piedmont, Italy

Sima Biswas, University of Kalyani

Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

Maria Talmon, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”

Department of Health Sciences, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, Novara, Piedmont, Italy

Filippo Patrucco, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”

Department of Translational Medicine, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, Novara, Piedmont, Italy

Department of Medical, Division of Respiratory Diseases, Azienda Ospedaliero Universitaria Maggiore della Carita, Novara, Piedmont, Italy

Piero Emilio Balbo, Azienda Ospedaliero Universitaria Maggiore della Carita

Department of Medical, Division of Respiratory Diseases, Azienda Ospedaliero Universitaria Maggiore della Carita, Novara, Piedmont, Italy

Luigia Grazia Fresu, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”

Department of Health Sciences, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, Novara, Piedmont, Italy

Angshuman Bagchi, University of Kalyani

Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

1.
Balasubramanian HB, Biswas S, Talmon M, Patrucco F, Balbo PE, Fresu LG, Bagchi A. Affinity of Nintedanib Towards New Candidate Target for Idiopathic Pulmonary Fibrosis. Borneo J Pharm [Internet]. 2024Aug.30 [cited 2024Dec.10];7(3):264-77. Available from: https://journal.umpr.ac.id/index.php/bjop/article/view/7218

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