ArticleInternational journal of molecular sciences2019
Insights into the Interaction Mechanisms of the Proviral Integration Site of Moloney Murine Leukemia Virus (Pim) Kinases with Pan-Pim Inhibitors PIM447 and AZD1208: A Molecular Dynamics Simulation and MM/GBSA Calculation Study.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- A systematic review on active sites and functions of PIM-1 protein.Human cell · 2022Pooled it
- Article
- Article
- Inhibition of PIM Kinases Promotes Neuroblastoma Cell Differentiation to a Neuronal Phenotype.Journal of pediatric surgery · 2023Article
- AUM302, a novel triple kinase PIM/PI3K/mTOR inhibitor, is a potent in vitro pancreatic cancer growth inhibitor.PloS one · 2023Article
- Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods.Frontiers in pharmacology · 2023Article
- The Role of PIM Kinases in Pediatric Solid Tumors.Cancers · 2022Review
- Article
- 'Targeting' the search: An upgraded structural and functional repository of antimicrobial peptides for biofilm studies (B-AMP v2.0) with a focus on biofilm protein targets.Frontiers in cellular and infection microbiology · 2022Article
- The Physical Chemistry and Chemical Physics (PCCP) Section of theInternational journal of molecular sciences · 2021Article
- PIM447 inhibits oncogenesis and potentiates cisplatin effects in hepatoblastoma.Journal of pediatric surgery · 2021Article
- Computational Insights Into the Effects of the R190K and N121Q Mutations on the SARS-CoV-2 Spike Complex With Biliverdin.Frontiers in molecular biosciences · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Based on the up-regulation of the proviral integration site of the Moloney murine leukemia virus (Pim) kinase family (Pim1, 2, and 3) observed in several types of leukemias and lymphomas, the development of pan-Pim inhibitors is an attractive therapeutic strategy. While only PIM447 and AZD1208 have entered the clinical stages. To elucidate the interaction mechanisms of three Pim kinases with PIM447 and AZD1208, six Pim/ligand systems were studied by homology modeling, molecular docking, molecular dynamics (MD) simulation and molecular mechanics/generalized Born surface area (MM/GBSA) binding free energy calculation. The residues of the top group (Leu44, Val52, Ala65, Lys67, and Leu120 in Pim1) dominated the pan-Pim inhibitors binding to Pim kinases. The residues of the bottom group (Gln127, Asp128, and Leu174 in Pim1) were crucial for Pims/PIM447 systems, while the contributions of these residues were decreased sharply for Pims/AZD1208 systems. It is likely that the more potent pan-Pim inhibitors should be bound strongly to the top and bottom groups. The residues of the left, right and loop groups were located in the loop regions of the binding pocket, however, the flexibility of these regions triggered the protein interacting with diverse pan-Pim inhibitors efficiently. We hope this work can provide valuable information for the design of novel pan-Pim inhibitors in the future.
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