ArticleJournal of computer-aided molecular design2012
Elaborate ligand-based modeling reveal new submicromolar Rho kinase inhibitors.
Article in Journal of computer-aided molecular design, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 38 citations in OpenAlex.
- Discovery of novel acridine based inhibitors of Bruton's tyrosine kinase (BTK) via pharmacophore modeling and machine learning-driven virtual screening followed by molecular dynamic studies.Journal of computer-aided molecular design · 2026Article
- Computational identification of potential VEGFR2 inhibitors using integrated pharmacophore modeling, QSAR analysis, molecular docking, dynamics simulation, and virtual screening followed by in vitro bioassays.Journal of computer-aided molecular design · 2026Article
- Computer-aided discovery of CDK16 inhibitors: a docking-augmented machine learning regression modelling approach.Journal of computer-aided molecular design · 2026Article
- Tracking protein kinase targeting advances: integrating QSAR into machine learning for kinase-targeted drug discovery.Future science OA · 2025Review
- Discovery of new Cdc2-like kinase 4 (CLK4) inhibitorsRSC advances · 2022Article
- Exploiting activity cliffs for building pharmacophore models and comparison with other pharmacophore generation methods: sphingosine kinase 1 as case study.Journal of computer-aided molecular design · 2022Article
- Design of novel ROCK inhibitors using fragment-based de novo drug design approach.Journal of molecular modeling · 2020Article
- Research advances in kinase enzymes and inhibitors for cardiovascular disease treatment.Future science OA · 2017Review
- Partial contribution of Rho-kinase inhibition to the bioactivity of Ganoderma lingzhi and its isolated compounds: insights on discovery of natural Rho-kinase inhibitors.Journal of natural medicines · 2017Article
- Combining molecular dynamics simulation and ligand-receptor contacts analysis as a new approach for pharmacophore modeling: beta-secretase 1 and check point kinase 1 as case studies.Journal of computer-aided molecular design · 2016Article
- Identification of novel inhibitors for Pim-1 kinase using pharmacophore modeling based on a novel method for selecting pharmacophore generation subsets.Journal of computer-aided molecular design · 2016Article
- The role of Rho/Rho-kinase pathway and the neuroprotective effects of fasudil in chronic cerebral ischemia.Neural regeneration research · 2015Article
- Elaborate ligand-based modeling coupled with QSAR analysis and in silico screening reveal new potent acetylcholinesterase inhibitors.Journal of computer-aided molecular design · 2013Article
- Potential benefits of rho-kinase inhibition in arterial hypertension.Current hypertension reports · 2013Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rho Kinase (ROCKII) has been recently implicated in several cardiovascular diseases prompting several attempts to discover and optimize new ROCKII inhibitors. Towards this end we explored the pharmacophoric space of 138 ROCKII inhibitors to identify high quality pharmacophores. The pharmacophoric models were subsequently allowed to compete within quantitative structure-activity relationship (QSAR) context. Genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of accessing self-consistent QSAR of optimal predictive potential (r (77) = 0.84, F = 18.18, r (LOO) (2) = 0.639, r (PRESS) (2) against 19 external test inhibitors = 0.494). Two orthogonal pharmacophores emerged in the QSAR equation suggesting the existence of at least two binding modes accessible to ligands within ROCKII binding pocket. Receiver operating characteristic (ROC) curve analyses established the validity of QSAR-selected pharmacophores. Moreover, the successful pharmacophores models were found to be comparable with crystallographically resolved ROCKII binding pocket. We employed the pharmacophoric models and associated QSAR equation to screen the national cancer institute (NCI) list of compounds Eight submicromolar ROCKII inhibitors were identified. The most potent gave IC(50) values of 0.7 and 1.0 μM.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.