Substituted pteridinones, pyrimidines, pyrrolopyrimidines, and purines as p90 ribosomal S6 protein kinase-2 (RSK2) inhibitors: Pharmacophore modeling data

Substituted pteridinones, pyrimidines, pyrrolopyrimidines, and purines as p90 ribosomal S6 protein kinase-2 (RSK2) inhibitors: Pharmacophore modeling data

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The RSK2 kinase is a downstream effector of the Ras/Raf/MEK/ERK pathway that is aberrantly active in a range of cancer types and has been recognized an anticancer target.The inhibition of RSK2 kinase activity would disrupt multiple pro-cancer processes; however, there are few RSK2 inhibitors.The data have been obtained for a series of pteridinone-, pyrimidine-, purine-, and pyrrolopyrimidine-based compounds, developed to establish a structure-activity relationship for RSK inhibition.The compounds were docked into the ATP-binding site of the N-terminal domain of the RSK2 kinase using Glide.

The binding conformations of these molecules was then used to generate a set of pharmacophore models to determine the structural requirements for RSK2 inhibition.Through the combination of cortech sonic-flo gloves these models, common features (pharmacophores) can be identified that can inform the development of further small molecule RSK inhibitors.The synthesis and evaluation of the pteridinone- and pyrimidine-based compounds was reported in the related articles: Substituted pteridinones as p90 ribosomal S6 protein kinase (RSK) jalkapallo asu inhibitors: A structure-activity study (Casalvieri et al., 2020) and Molecular docking of substituted pteridinones and pyrimidines to the ATP-binding site of the N-terminal domain of RSK2 and associated MM/GBSA and molecular field datasets (Casalvieri et al.

, 2020).[1,2].The synthesis and evaluation of the purine- and pyrrolopyrimidine-based compounds was reported in the related research article: N-substituted pyrrolopyrimidines and purines as p90 ribosomal S6 protein kinase-2 (RSK2) inhibitors (Casalvieri et al., 2021) [3].