Computer aided Drug Designing for the identification of high affinity small molecule targeting CD20 for the clinical treatment of Chronic Lymphocytic Leukemia (CLL)

(E-pub Abstract Ahead of Print)

Author(s): Kritika Sinha, Manisha Majhi, Garima Thakur, Khushboo Patidar, Jajoriya Sweta, Anuraj Nayarisseri*, Sanjeev Kumar Singh.

Journal Name: Current Topics in Medicinal Chemistry


Background: Chronic lymphocytic leukemia (CLL) is a B-lineage lymphoid malignancy of self-reactive cells that are focused to produce polyreactive natural auto antibodies. Its surface protein marker CD20 plays an important role in the humoral immune response, targeting which have emerged as an attractive therapeutic option for the treatment of CLL. The present study explains the interaction of the CD20 with its established inhibitors and to discover the compound having high binding affinity against the target protein receptor. Technically, in the development to new compound through docking studies got filtered best drug among all pre-exist drugs hence in reference of docked best drug study moved ahead.

Methods: The 3D structure of CD20 was built using homology base fold recognition method using Smith waterman’s Local alignment and standalone Delta Blast algorithms. 23 established inhibitors towards CD20 were selected in this present investigation. Among these inhibitors, etoposide (RMSD value -96.6481) showed high binding capacity with the receptor CD20 which was further subjected to virtual screening. The said screening presented 380 possible drugs having structural similarity to etoposide.

Results: The docking studies of the screened drugs separated the compound having PubChem CID: 11753896 (RMSD value -98.5416). Toxicity and interaction profile validated this compound for having better affinity with the target protein. Conclusively, this research study says that according to ADMET profile and BOILED-Egg plot, the compound (PubChem CID: 11753896) obtained from Virtual Screen could be a future best drug in prevention of Chronic Lymphocytic Leukemia.

Conclusion: The compound identified in the present investigation can be subjected further for In vitro and In vivo studies for ADMET properties and it could optimize a good profile in the field of pharmacy and bioavailable for suppressing cancer. The pharmacophore study revealed that the drug CID11753896 is a non-inhibitor of CYP450 microsomal enzymes and was found to be non-toxic, similar to the established compound CID36462. It has lower LD50 value of 2.5423mol/kg as compared to the established compound whose LD50 value is 2.9588mol/kg. Also the compound was found to be non-carcinogenic.

Keywords: Chronic Lymphocytic Leukemia, CD20, Molecular modeling, MODELLER, Molecular Docking, Virtual Screening, BOILED-Egg plot

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(E-pub Abstract Ahead of Print)
DOI: 10.2174/1568026619666181210150044
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