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

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...

Full description

Saved in:
Bibliographic Details
Published in:Bioinformation 2019, Vol.15 (2), p.104-115
Main Authors: Gokhale, Padmini, Chauhan, Aashish Pratap Singh, Arora, Anushka, Khandekar, Natasha, Nayarisseri, Anuraj, Singh, Sanjeev Kumar
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Bone cancer
Bone marrow
Cancer
Comparative studies
Erythrocytes
Flt3 protein
Inhibitors
Kinases
Leukemia
Molecular docking
Myeloid leukemia
Pharmacology
Protein-tyrosine kinase
Proteins
Screening
Therapeutic applications
Tyrosine
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 secondgeneration 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 bestestablished candidate Quizartinib having PubChem CID: 24889392. Similarity searching resulted in compound XGIQBUNWFCCMASUHFFFAOYSA-NPubChemCID: 44598530 which shows higher affinity 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 predicted the ligand to be an efficient inhibitor of FLT3.
ISSN:0973-2063
0973-8894
0973-2063
DOI:10.6026/97320630015104