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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

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

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Frontiers in Molecular Biosciences

ISSN

2296-889X

e-ISSN

2296-889X

Svazek periodika

11

Číslo periodika v rámci svazku

OCT 15 2024

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

15

Strana od-do

—

Kód UT WoS článku

001343765800001

EID výsledku v databázi Scopus

2-s2.0-85208631120