Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Tackling the Moving Mutant Target: Taxifolin Derivatives as Novel Putative E571K Exportin-1 Inhibitors for KRAS-mutant Lung Adenocarcinoma Therapy

Temidayo Adigun
* ,
Oluwatobi Medayedupin
,
Ireoluwa Joel
,
Idowu Fakolujo
,
Bankole Ofeniforo
,
Faith Bankole
,
Adedayo Omoniyi
,
Olalekan Ogunro
,
Adebimpe Agunlejika
,
Oluwatobi Omoyeni
,
Joy Bamidele
,
Adetola Ajayi
Version 1 : Received: 30 December 2020 / Approved: 31 December 2020 / Online: 31 December 2020 (12:25:13 CET)

How to cite: Adigun, T.; Medayedupin, O.; Joel, I.; Fakolujo, I.; Ofeniforo, B.; Bankole, F.; Omoniyi, A.; Ogunro, O.; Agunlejika, A.; Omoyeni, O.; Bamidele, J.; Ajayi, A. Tackling the Moving Mutant Target: Taxifolin Derivatives as Novel Putative E571K Exportin-1 Inhibitors for KRAS-mutant Lung Adenocarcinoma Therapy. Preprints 2020, 2020120797. https://doi.org/10.20944/preprints202012.0797.v1 Adigun, T.; Medayedupin, O.; Joel, I.; Fakolujo, I.; Ofeniforo, B.; Bankole, F.; Omoniyi, A.; Ogunro, O.; Agunlejika, A.; Omoyeni, O.; Bamidele, J.; Ajayi, A. Tackling the Moving Mutant Target: Taxifolin Derivatives as Novel Putative E571K Exportin-1 Inhibitors for KRAS-mutant Lung Adenocarcinoma Therapy. Preprints 2020, 2020120797. https://doi.org/10.20944/preprints202012.0797.v1

Abstract

Aim: To establish, through molecular modelling, safe and clinically acceptable putative antagonists of E571K-mutated exportin-1 among the bioactive compounds in various parts of Juglans mandshurica. Methods: The bioactive compounds were subjected to compendium of druglikeness and lead-likeness filter workflows prior to docking of the resultant compounds into E571K exportin-1 active site using PyRx AutoDock vina to establish their binding affinity and interaction profile. The evolutionary algorithm of Osiris property explorer DataWarrior software as well as lead-likeness filter were employed for generation of novel non-promiscuous analogues of the lead compound with better putative selectivity and clinical acceptability as E571K Exportin-1 antagonists.Results: The findings of this study present taxifolin as the putatively effective and lead-like E571K Exportin-1 inhibitor with high potential of qualifying for clinical evaluation but is associated with high promiscuity tendency in high throughput screening. The evolutionary derivation of novel analogues of the compound, however, results in the generation of putatively non-promiscuous, non-toxic, and lead-like E571K Exportin-1 antagonists with high synthetic accessibility and clinical developability for evaluation in the strategy for treatment of drug-resistant KRAS-mutant lung adenocarcinoma condition.

Keywords

KRAS-mutant lung adenocarcinoma; E571K exportin-1; Taxifolin; Molecular modelling

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.