FMS-like tyrosine kinase-3 (FLT3) inhibitors with better binding affinity and ADMET properties than sorafenib and gilteritinib against acute myeloid leukemia: in silico studies

Simple item page
dc.contributor.authorEgbuna, Chukwuebuka
dc.contributor.authorPatrick-Iwuanyanwu, Kingsley C.
dc.contributor.authorOnyeike, Eugene N.
dc.date.accessioned2023-05-15T13:33:41Z
dc.date.available2023-05-15T13:33:41Z
dc.date.issued2021-09-06
dc.description.abstractOver 30–35% of patients down with AML are caused by mutations of FLT3-ITD and FLT3-TKD which keeps the protein activated while it activates other signaling proteins downstream that are involved in cell proliferation, differentiation, and survival. As drug targets, many inhibitors are already in clinical practice. Unfortunately, the average overall survival rate for patients on medication suffering from AML is 5 years despite the huge efforts in this field. To perform docking simulation and ADMET studies on selected phytochemicals against FLT3 protein receptor for drug discovery against FLT3 induced AML, molecular docking simulation was performed using human FLT3 protein target (PDB ID: 6JQR) and 313 phytochemicals with standard anticancer drugs (Sorafenib and Gilteritinib in addition to other anticancer drugs). The crystal structure of the protein was downloaded from the protein data bank and prepared using Biovia Discovery Studio. The chemical structures of the phytochemicals were downloaded from the NCBI PubChem database and prepared using Open Babel and VConf softwares. Molecular docking was performed using PyRx on Autodock Vina. The ADMET properties of the bestperforming compounds were calculated using SwissADME and pkCMS web servers. The results obtained showed that glabridin, ellipticine and derivatives (elliptinium and 9-methoxyellipticine),mezerein, ursolic acid, formononetin, cycloartocarpesin, hypericin, silymarin, and indirubin are the best performing compounds better than sorafenib and gilteritinib based on their binding affinities. The top-performing compounds which had better binding and ADMET properties than sorafenib and gilteritinib could serve as scaffolds or leads for new drug discovery against FLT3 induced AMen_US
dc.description.sponsorshipACE: Public Health and Toxicological Researchen_US
dc.identifier.citationChukwuebuka Egbuna, Kingsley C. Patrick-Iwuanyanwu, Eugene N. Onyeike, Johra Khan & Bader Alshehri (2022) FMS-like tyrosine kinase-3 (FLT3) inhibitors with better binding affinity and ADMET properties than sorafenib and gilteritinib against acute myeloid leukemia: in silico studies, Journal of Biomolecular Structure and Dynamics, 40:22, 12248-12259, DOI: 10.1080/07391102.2021.1969286en_US
dc.identifier.issn0739-1102
dc.identifier.issn1538-0254
dc.identifier.urihttp://hdl.handle.net/123456789/1781
dc.language.isoenen_US
dc.publisherTaylor and Francisen_US
dc.relation.ispartofseriesJournal of Biomolecular Structure and Dynamics;VOL. 40, NO. 22
dc.subjectFms-like tyrosine kinase 3en_US
dc.subjectacute myeloid leukemiaen_US
dc.subjectmutationen_US
dc.subjectcancer of the blood;en_US
dc.subjectmolecular docking simulationen_US
dc.subjectbioactive compoundsen_US
dc.subjectBader Alshehrien_US
dc.subjectUniversity of Port Harcourten_US
dc.subjectACE-PUTORen_US
dc.subjectACE: Public Health and Toxicological Researchen_US
dc.titleFMS-like tyrosine kinase-3 (FLT3) inhibitors with better binding affinity and ADMET properties than sorafenib and gilteritinib against acute myeloid leukemia: in silico studiesen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
FMS like tyrosine kinase.pdf
Size:
2.84 MB
Format:
Adobe Portable Document Format
Description:
Main article
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Health