Identification of potential bioactive phytochemicals for the inhibition of platelet-derived growth factor receptor β - a structure-based approach for cancer therapy

Sep 21, 2026

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Platelet-derived growth factor receptor beta (PDGFRβ) is a receptor tyrosine kinase implicated in multiple cancers and non-cancer disorders, and it is overexpressed during tumor progression. Although small-molecule inhibitors targeting PDGFRβ show promise, clinical translation remains limited and interaction mechanisms, as well as specificity and selectivity, are not fully resolved. This structure-based study identifies two compounds, Genostrychnine and Chelidonine, using Lipinski’s rule of five, 2D similarity search, 3D pharmacophore-based virtual screening, and molecular dynamics simulations to assess binding and inhibition potential.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Receptor tyrosine kinases (RTKs) and PDGFRβ background

Study rationale and current knowledge gaps

Compound discovery and screening workflow (RO5, 2D/3D screening, MD simulation)

TYPE Original Research PUBLISHED 15 October 2024 DOI 10.3389/fmolb.2024.1492847 OPEN ACCESS EDITED BY Timir Tripathi, North Eastern Hill University, India REVIEWED BY Chang Liu, The University of Texas at Austin, United States Raghavendra Nagampalli, St. Jude Children’s Research Hospital, United States Naushad Khan, Jackson Laboratory for Genomic Medicine, United States *CORRESPONDENCE Imtaiyaz Hassan, [mihassan@jmi.ac.in](mihassan@jmi.ac.in)[ ](mihassan@jmi.ac.in)Anas Shamsi, [anas.shamsi18@gmail.com](anas.shamsi18@gmail.com) †These authors have contributed equally to this work RECEIVED 08 September 2024 ACCEPTED 30 September 2024 PUBLISHED 15 October 2024 CITATION Habib I, Sulaimani MN, Jairajpuri DS, Hussain A, Mohammad T, Alajmi MF, Shamsi A and Hassan MI (2024) Identification of potential bioactive phytochemicals for the inhibition of platelet-derived growth factor receptor β: a structure-based approach for cancer therapy. Front. Mol. Biosci. 11:1492847. doi: 10.3389/fmolb.2024.1492847 COPYRIGHT © 2024 Habib, Sulaimani, Jairajpuri, Hussain, Mohammad, Alajmi, Shamsi and Hassan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Identification of potential bioactive phytochemicals for the inhibition of platelet-derived growth factor receptor β: a structure-based approach for cancer therapy Insan Habib 1,2†, Md Nayab Sulaimani 2†, Deeba Shamim Jairajpuri 3, Afzal Hussain 4, Taj Mohammad 2, Mohamed F. Alajmi 4, Anas Shamsi 5* and Md Imtaiyaz Hassan 2* 1 Department of Parasitology, Faculty of Science, University of South Bohemia, Ceske Budejovice, Czechia, 2Centre for Interdisciplinary Research in Basic Sciences, New Delhi, India, 3 Department of Medical Biochemistry, College of Medicine and Health Sciences, Arabian Gulf University, Manama, Bahrain, 4 Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, 5Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates Platelet-derived growth factor receptor beta (PDGFRβ) belongs to the receptor tyrosine kinase (RTK) protein family and is implicated in several disorders such as hematopoietic, glial, and soft-tissue cancer, non-cancerous disorders, including skeletal defects, brain calcification, and vascular anomalies. The research on small molecule inhibitors targeting PDGFRβ in cancer treatment has seen promising developments, but significant gaps remain. PDGFRβ, receptor tyrosine kinase, is overexpressed in various cancers and plays an important role in tumor progression, making it a potential therapeutic target. However, despite advances in identifying and characterizing PDGFRβ inhibitors, few have progressed to clinical trials, and the mechanistic details of PDGFRβ′s interactions with small molecule inhibitors are still not fully understood. Moreover, the specificity and selectivity of these inhibitors remain challenging, as off-target effects can lead to unwanted toxicity. In this investigation, two compounds, Genostrychnine and Chelidonine, were discovered that help inhibit the kinase activity of PDGFRβ . These small molecules were identified by employing various parameters involved in the drug discovery process, such as Lipinski’s rule of five (RO5), 2D similarity search and 3D pharmacophorebased virtual screening followed by MD simulation studies. The identified molecules were found to be effective and significantly bound with the Abbreviations: PDGFRβ, Platelet-derived growth factor receptor beta; RTK, Receptor tyrosine kinase; MD, Mo

FAQs

Why is PDGFRβ considered a therapeutic target in cancer therapy?

PDGFRβ is a receptor tyrosine kinase overexpressed in various cancers and contributes to tumor progression, making it a promising therapeutic target.

Which compounds were identified as potential PDGFRβ inhibitors in this study?

Genostrychnine and Chelidonine were discovered and evaluated as small molecules that inhibit PDGFRβ kinase activity.

What computational steps were used to identify and validate the candidate molecules?

The workflow included Lipinski’s rule of five filtering, 2D similarity search, 3D pharmacophore-based virtual screening, followed by molecular dynamics simulations to study binding and interaction behavior.

Sep 21, 2026

Uploaded by Skyler