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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F24%3A43908778" target="_blank" >RIV/60076658:12310/24:43908778 - isvavai.cz</a>

Result on the web

<a href="https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1492847/full" target="_blank" >https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1492847/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fmolb.2024.1492847" target="_blank" >10.3389/fmolb.2024.1492847</a>

Result language

angličtina

Original language name

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

Original language description

Platelet-derived growth factor receptor beta (PDGFR beta) 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 PDGFR beta in cancer treatment has seen promising developments, but significant gaps remain. PDGFR beta, 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 PDGFR beta inhibitors, few have progressed to clinical trials, and the mechanistic details of PDGFR beta &apos; 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 PDGFR beta. These small molecules were identified by employing various parameters involved in the drug discovery process, such as Lipinski&apos;s rule of five (RO5), 2D similarity search and 3D pharmacophore-based virtual screening followed by MD simulation studies. The identified molecules were found to be effective and significantly bound with the PDGFR beta kinase domain. Overall, our findings demonstrate that these small drug-like compounds can be beneficial tools in studying the properties of PDGFR beta and can play a crucial role in the therapeutic development of cancers and other associated diseases.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Molecular Biosciences

ISSN

2296-889X

e-ISSN

2296-889X

Volume of the periodical

11

Issue of the periodical within the volume

OCT 15 2024

Country of publishing house

CH - SWITZERLAND

Number of pages

15

Pages from-to

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UT code for WoS article

001343765800001

EID of the result in the Scopus database

2-s2.0-85208631120