Computational Design and Study of a Series of Compounds as Potential Ribosomal S6 Kinase Inhibitors with Reduced Side Effects

Abstract

Cancer is a disease where abnormal multiplication of cell occur, Different types of cancer such as lung cancer, breast cancer, colon cancer are causing large

number of deaths of human. Kinases are proteins involved in phosphorylation, Ribo- somal S6 Kinase (RSK) plays a vital role in development of cancer. These kinases are

posing a challenge for treatment of cancer. Here, we investigated the different types of cancer caused by RSK, 375 PKIS Compounds are docked against RSKs whose glide

score predicted they are stronger kinase inhibitor with interaction like Cation interac- tion , Hydrophobic interaction, Hydrogen Bonding among them stronger interaction

shown by CHEMBL103104 with glide score of -10.7 CHEMBL103115 with glide score of -10.63 CHEMBL208437 with glide score of -10.05 CHEMBL175321 with

glide score of -9.9 CHEMBL 1909351 with glide score of -9.67. Fragment based dock- ing predict these are good inhibitors of RSKs as their glide score vary from -10.09

to -6.35 with interaction shown like Hydrophobic interaction, cation interaction. Co- crystallized ligands, and Standard inhibitors docking improved their interaction with

binding site with glide scores vary from -9.39 to -6.39 and -9.9 to -7.4 respectively. PKIS predicted as stronger inhibitor with very high glide score, following Fragments, co-crystallized, and standard inhibitors. We Designed new Inhibitors named KH-1- KH-9 that have maximum Protein Ligand interactions with glide scores vary from -10 to -8. We propose, that newly designed inhibitors can be used to inhibit the primary site of RSKs causing cancers.