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ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. Structural Biology
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1492847

Identification of Potential Bioactive Phytochemicals for the Inhibition of Platelet-Derived Growth Factor Receptor β: A Structure-based Approach for Cancer Therapy

Provisionally accepted
Insan Habib Insan Habib 1Nayab Sulaimani Nayab Sulaimani 2Dr Afzal Hussain Dr Afzal Hussain 3Taj Mohammad Taj Mohammad 2Mohamed AlAjmi Mohamed AlAjmi 3Anas Shamsi Anas Shamsi 4*Md. I. Hassan Md. I. Hassan 2*
  • 1 University of South Bohemia in České Budějovice, České Budějovice, South Bohemia, Czechia
  • 2 Jamia Millia Islamia, New Delhi, India
  • 3 King Saud University, Riyadh, Riyadh, Saudi Arabia
  • 4 Ajman University, Ajman, Ajman, United Arab Emirates

The final, formatted version of the article will be published soon.

    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 stimulate the kinase activity 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 very effective and significantly stimulated the PDGFRβ activity. Overall, our findings demonstrate that these small drug-like compounds can be beneficial tools in studying the properties of PDGFRβ and can play a crucial role in the therapeutic development of cancers and other associated diseases.

    Keywords: Platelet-derived growth factor receptor beta, phytochemicals, Virtual Screening, Molecular Dynamics Simulation, Essential dynamics Platelet-derived growth factor receptor beta, PDGFRβ, Receptor tyrosine kinase, RTK, Molecular dynamics, MD, High mobility group box 1, HMGB1

    Received: 08 Sep 2024; Accepted: 30 Sep 2024.

    Copyright: © 2024 Habib, Sulaimani, 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) or licensor 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.

    * Correspondence:
    Anas Shamsi, Ajman University, Ajman, Ajman, United Arab Emirates
    Md. I. Hassan, Jamia Millia Islamia, New Delhi, India

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