English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

B-cell chronic lymphocytic leukemia (CLL) is the most prevalent B-cell malignancy in adults. Despite advances in treatment, the disease remains incurable, warranting further efforts to identify novel molecular targets and inhibitors. Spleen tyrosine kinase (SYK) plays a pivotal role for B-lymphocyte development and maturation in the B-cell receptor (BCR) signaling pathway and hence represents a potential therapeutic target for CLL. The present study is directed towards finding novel inhibitors of SYK through ligand based virtual screening. The co-crystal structure of SYK was investigated to locate active site residues (Glu-449, Ala-451 Arg-498, Asn-499, Ser-511, and Asp-512). Five SYK specific published inhibitors (Gleevec, staurosporine, Bay61-3606, R-406 and p5c) were explored against more than one million entries of the Ligand.Info metadatabase to create an in-house library of 1957 structural analogs. Ligand dataset was prepared using LigPrep and filtered based on Lipinski&#x2019;s rule of five and reactive group constraints. Docking using Computational Glide v5.5 from lesser to higher stringency towards minor steric classes were applied subsequently to the prepared ligand dataset against a grid around the centroid of the SYK active site. Fifteen lead molecules with good binding affinity to SYK were identified and compared with binding affinities and orientations of five published inhibitors. Apigenin (-10.05 Kcal/mol) and Glafenine (-9.72 Kcal/mol) endeavored better binding affinities, hydrogen bonding network and Van der Waal interactions with active site residues compared to published inhibitors. Thus, Apigenin and Glafenine would be valuable for designing a novel inhibitor against CLL, if synthesized and tested in vitro and in vivo

Docking studies to explore novel lead molecules for human Spleen tyrosine kinase involved in chronic lymphocytic leukemia