Pharmacophore based High Throughput Virtual Screening towards the Discovery of Novel BLK (B-lymphocyte kinase)- tyrosine Kinase Inhibitors

Abstract: Aim: LK (B-lymphocyte kinase) is a protein from the family SRC (Proto-oncogene tyrosine-protein kinase), an important cell signaling molecule that influences cellular response. The BLK kinase has been potential target for cancer therapy. As result, this could be initial step toward development of novel inhibitors to fight cancer. Materials and Methods: A homology model human tyrosine was constructed using Phyre2. Active site prediction done CASTp server. High Throughput virtual screening performed with help ligand-based pharmacophore FDA (Food Drug Administration) approved PharmaGist ZINCPharmer servers. 250 compounds obtained were docked by Python script-based method Autodock Vina. To ensure drug safety, ADME/Tox (Absorption, Distribution, Metabolism, Elimination, Toxicity) analysis molecules lowest binding energy. Six passed again utilized perform molecular docking Autodock4. active residues then identified PLIP [protein ligand interaction profiler]. Results Conclusion: analysis. Based on analysis, compound ZINC57306994 showed increased affinity kinase. may serve as lead developed into potent inhibitor. Keywords: Pharmacophore modeling, Molecular docking, kinase, Cancer.