Title

FLT3 inhibitor design using molecular docking based virtual screening for acute myeloid leukemia

Authors

Padmini Gokhale¹, Aashish Pratap Singh Chauhan¹, Anushka Arora¹, Natasha Khandekar¹, Anuraj
Nayarisseri^*,1,2,3, Sanjeev Kumar Singh^*,3

Affiliation

¹In silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh, India.; ²Bioinformatics Research Laboratory, LeGene Biosciences Pvt Ltd., Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, India. ³Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi-630 003, Tamil Nadu, India.

Email

Dr. Sanjeev Kumar Singh – Email: skysanjeev@gmail.com; Dr. Anuraj Nayarisseri - Email: anuraj@eminentbio.com; *Corresponding authors:

Article Type

Research Article

Date

Received January 27, 2019; Revised February 10, 2019; Accepted February 19, 2019; Published February 28, 2019

Acute Myeloid Leukaemia (AML) is a blood cancer, which affects the red blood cells in the bone marrow. Of the possible proteins that are affected in AML, fms-like tyrosine kinase 3 (FLT3) has long been recognized as a potential therapeutic target as it affects the other signaling pathways and leads to a cascade of events. First-generation inhibitors sorafenib and midostaurin, as well as second generation agents such as quizartinib and crenolanib are known. It is of interest to identify new compounds against FLT3 with improved activity using molecular docking and virtual screening. Molecular docking of existing inhibitors selected a top scoring best established candidate Quizartinib having PubChem CID: 24889392. Similarity searching resulted in compound XGIQBUNWFCCMASUHFFFAOYSA-N PubChemCID: 44598530 which shows higher affinityy scores. A comparative study of both the compounds using a drug-drug comparison, ADMET studies, boiled egg plot and pharmacophore parameters and properties confirmed the result and predict the ligand to be an efficient inhibitor of FLT3.

Keywords

FLT3 Inhibitors, Acute Myeloid Leukemia, Molecular Docking, Virtual Screening.

Citation

Gokhale et al. Bioinformation 15(2): 104-115 (2019)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.