ArticlePLoS computational biology2011
Drug discovery using chemical systems biology: weak inhibition of multiple kinases may contribute to the anti-cancer effect of nelfinavir.
Article in PLoS computational biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 172 citations in OpenAlex.
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- The Discovery of New Drug-Target Interactions for Breast Cancer Treatment.Molecules (Basel, Switzerland) · 2021Article
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- Off-Target-Based Design of Selective HIV-1 PROTEASE Inhibitors.International journal of molecular sciences · 2021Article
- CAVIAR: a method for automatic cavity detection, description and decomposition into subcavities.Journal of computer-aided molecular design · 2021Article
- HIV-1 Protease Inhibitors Slow HPV16-Driven Cell Proliferation through Targeted Depletion of Viral E6 and E7 Oncoproteins.Cancers · 2021Article
- Machine learning approaches and databases for prediction of drug-target interaction: a survey paper.Briefings in bioinformatics · 2021Review
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- cando.py: Open Source Software for Predictive Bioanalytics of Large Scale Drug-Protein-Disease Data.Journal of chemical information and modeling · 2020Article
- New drugs are not enough‑drug repositioning in oncology: An update.International journal of oncology · 2020Review
- Drug-target interaction prediction using Multi Graph Regularized Nuclear Norm Minimization.PloS one · 2020Article
- Multi-channel PINN: investigating scalable and transferable neural networks for drug discovery.Journal of cheminformatics · 2019Article
- Rational discovery of dual-indication multi-target PDE/Kinase inhibitor for precision anti-cancer therapy using structural systems pharmacology.PLoS computational biology · 2019Article
- A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs).PLoS computational biology · 2018Article
- Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents.PLoS computational biology · 2018Article
- Computational Cell Cycle Profiling of Cancer Cells for Prioritizing FDA-Approved Drugs with Repurposing Potential.Scientific reports · 2017Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
Abstract
Nelfinavir is a potent HIV-protease inhibitor with pleiotropic effects in cancer cells. Experimental studies connect its anti-cancer effects to the suppression of the Akt signaling pathway, but the actual molecular targets remain unknown. Using a structural proteome-wide off-target pipeline, which integrates molecular dynamics simulation and MM/GBSA free energy calculations with ligand binding site comparison and biological network analysis, we identified putative human off-targets of Nelfinavir and analyzed the impact on the associated biological processes. Our results suggest that Nelfinavir is able to inhibit multiple members of the protein kinase-like superfamily, which are involved in the regulation of cellular processes vital for carcinogenesis and metastasis. The computational predictions are supported by kinase activity assays and are consistent with existing experimental and clinical evidence. This finding provides a molecular basis to explain the broad-spectrum anti-cancer effect of Nelfinavir and presents opportunities to optimize the drug as a targeted polypharmacology agent.
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Registered trials
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.