Identification of novel BRD4 inhibitors by pharmacophore screening, molecular docking, and molecular dynamics simulation

Dong, Junmin; Wang, Xinghe

doi:10.1016/j.molstruc.2022.134363

Cited by 4 publications

(1 citation statement)

References 54 publications

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“…The changes in Dolastatin 16 complex were evaluated and compared between the different systems. The conformational changes of protein-ligand complexes during the simulation can be analyzed by RMSD (Dong and Wang 2023). Figure 8a represents the RMSD-Cα plots for native protein MMP9 and protein-ligand complexes.…”

Section: Al (R)-nd-336 Exhibited Greater E Cacy Overmentioning

confidence: 99%

Network Pharmacology Reveals the Potential of Dolastatin 16 as Diabetic Wound Healing Agent

Luthfiana,

Utomo

2023

Preprint

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Dolastatin 16, a marine cyclic depsipeptide, was first isolated from the sea hare Dolabella Auricularia by Pettit et al. Since its bioactivity lacks of information, target identification is the indispensable strategy to reveal the potential target and mechanism of action of Dolastatin 16. Network pharmacology was utilized to identify the target associated with the disease, gene ontology, and KEGG pathway. The results demonstrated Matrix Metalloproteinase-9 (MMP9) as a potential target of Dolastatin 16 via network pharmacology analysis. The target was also mainly involved in TNF signaling pathway and foot ulceration-associated diabetic polyneuropathy. Further, the binding mode and dynamic behavior of the complex was investigated by molecular docking and molecular dynamics studies. In docking study, a native ligand (a hydroxamate inhibitor) and (R)-ND-336 were used as the ligand controls, demonstrating the binding energies of -6.6 and − 8.9 kcal/mol, respectively. The Dolastatin 16 complex showed the lowest binding energy of -9.7 kcal/mol, suggesting its higher potential as an inhibitor. Molecular dynamics also validated the stability of MMP9-Dolastatin complex throughout the simulation process. Dolastatin 16 may act as a MMP9 inhibitor and have potential to accelerate the wound healing process in diabetic foot condition.

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Section: Al (R)-nd-336 Exhibited Greater E Cacy Overmentioning

confidence: 99%

Network Pharmacology Reveals the Potential of Dolastatin 16 as Diabetic Wound Healing Agent

Luthfiana,

Utomo

2023

Preprint

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Network pharmacology reveals the potential of Dolastatin 16 as a diabetic wound healing agent

Luthfiana,

Utomo

2023

In Silico Pharmacol.

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Discovery of Potential Inhibitors of CDK1 by Integrating Pharmacophore-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation Studies, and Evaluation of Their Inhibitory Activity

Teotia,

Jha,

Chopra

2024

ACS Omega

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The ability of CDK1 to compensate for the absence of other cell cycle CDKs poses a great challenge to treat cancers that overexpress these proteins. Despite several studies focusing on the area, there are no FDAapproved drugs selectively targeting CDK1. Here, the study aimed to develop potential CDK1 selective inhibitors through drug repurposing and leveraging the structural insights provided by the hit molecules generated. Approximately 280,000 compounds from DrugBank, Selleckchem, Otava and an in-house library were screened initially based on fit values using 3D QSAR pharmacophores built for CDK1 and subsequently through Lipinski, ADMET, and TOPKAT filters. 10,310 hits were investigated for docking into the binding site of CDK1 determined using the crystal structure of human CDK1 in complex with NU6102. The best 55 hits with better docking scores were further analyzed, and 12 hits were selected for 100 ns MD simulations followed by binding energy calculations using the MM-PBSA method. Finally, 10 hit molecules were tested in an in vitro CDK1 Kinase inhibition assay. Out of these, 3 hits showed significant CDK1 inhibitory potential with IC 50 < 5 μM. These results indicate these compounds can be used to develop subtype-selective CDK1 inhibitors with better efficacy and reduced toxicities in the future.

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Identification of novel BRD4 inhibitors by pharmacophore screening, molecular docking, and molecular dynamics simulation

Cited by 4 publications

References 54 publications

Network Pharmacology Reveals the Potential of Dolastatin 16 as Diabetic Wound Healing Agent

Network Pharmacology Reveals the Potential of Dolastatin 16 as Diabetic Wound Healing Agent

Network pharmacology reveals the potential of Dolastatin 16 as a diabetic wound healing agent

Discovery of Potential Inhibitors of CDK1 by Integrating Pharmacophore-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation Studies, and Evaluation of Their Inhibitory Activity

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