Pharmacophore modeling, virtual screening, molecular docking and dynamics studies for the discovery of HER2-tyrosine kinase inhibitors: An in-silico approach

Matada, Gurubasavaraja S.P.; Dhiwar, Prasad Sanjay; Abbas, Nahid; Singh, Ekta; Ghara, Abhishek; Patil, Rajesh B.; Raghavendra, Narasimha

doi:10.1016/j.molstruc.2022.132531

Cited by 9 publications

(1 citation statement)

References 73 publications

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“…To create a pharmacophore model, we used previously published FOXM1 inhibitor FDI-6 [ 17 , 24 ]. The features of pharmacophore were determined using the BIOVIA Discovery Studio 2021 (DS 2021) Auto Pharmacophore Generation module [ 25 – 27 ]. This pharmacophore model was used as a three-dimensional (3D) query to search for matching hits from approved drug databases.…”

Section: Methodsmentioning

confidence: 99%

A drug repurposing study identifies novel FOXM1 inhibitors with in vitro activity against breast cancer cells

Abusharkh,

Comert Onder,

Çınar

et al. 2024

Med Oncol

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FOXM1, a proto-oncogenic transcription factor, plays a critical role in cancer development and treatment resistance in cancers, particularly in breast cancer. Thus, this study aimed to identify potential FOXM1 inhibitors through computational screening of drug databases, followed by in vitro validation of their inhibitory activity against breast cancer cells. In silico studies involved pharmacophore modeling using the FOXM1 inhibitor, FDI-6, followed by virtual screening of DrugBank and Selleckchem databases. The selected drugs were prepared for molecular docking, and the crystal structure of FOXM1 was pre-processed for docking simulations. In vitro studies included MTT assays to assess cytotoxicity, and Western blot analysis to evaluate protein expression levels. Our study identified Pantoprazole and Rabeprazole as potential FOXM1 inhibitors through in silico screening and molecular docking. Molecular dynamics simulations confirmed stable interactions of these drugs with FOXM1. In vitro experiments showed both Pantoprazole and Rabeprazole exhibited strong FOXM1 inhibition at effective concentrations and that showed inhibition of cell proliferation. Rabeprazole showed the inhibitor activity at 10 µM in BT-20 and MCF-7 cell lines. Pantoprazole exhibited FOXM1 inhibition at 30 µM and in BT-20 cells and at 70 µM in MCF-7 cells, respectively. Our current study provides the first evidence that Rabeprazole and Pantoprazole can bind to FOXM1 and inhibit its activity and downstream signaling, including eEF2K and pEF2, in breast cancer cells. These findings indicate that rabeprazole and pantoprazole inhibit FOXM1 and breast cancer cell proliferation, and they can be used for FOXM1-targeted therapy in breast or other cancers driven by FOXM1. Graphical Abstract

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Section: Methodsmentioning

confidence: 99%

A drug repurposing study identifies novel FOXM1 inhibitors with in vitro activity against breast cancer cells

Abusharkh,

Comert Onder,

Çınar

et al. 2024

Med Oncol

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Nitrogen‐Containing Heterocyclic Scaffolds as EGFR Inhibitors: Design Approaches, Molecular Docking, and Structure‐Activity Relationships

Pal¹,

Teli²,

Matada³

et al. 2023

ChemistrySelect

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proved to be the magical weapon in designed and discovery of synthetic molecules as they acquired comprehensive range of pharmacological properties. In recent year (2018-2022) Nheterocyclic derivatives were uncovered as the potential EGFR TKIs. The present review summarised the research progress of EGFR TKIs to dazed the limitations of currently accessible drugs by consecrating, anatomy, mutation of EGFR, and its role in different types of cancer. The review highlights the medicinal chemistry prospective emphasising about the designing strategies, docking studies, biological evaluation, selectivity and structural activity relationship of N-heterocyclic compounds. Our review will support the medicinal chemists in direction for the development of novel N-heterocyclic based EGFR TKIs.

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Structural optimization of pyrrolopyrimidine BTK inhibitors based on molecular simulation

Wu,

Li,

Chen

et al. 2023

J Mol Model

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Pharmacophore modeling, virtual screening, molecular docking and dynamics studies for the discovery of HER2-tyrosine kinase inhibitors: An in-silico approach

Cited by 9 publications

References 73 publications

A drug repurposing study identifies novel FOXM1 inhibitors with in vitro activity against breast cancer cells

A drug repurposing study identifies novel FOXM1 inhibitors with in vitro activity against breast cancer cells

Nitrogen‐Containing Heterocyclic Scaffolds as EGFR Inhibitors: Design Approaches, Molecular Docking, and Structure‐Activity Relationships

Structural optimization of pyrrolopyrimidine BTK inhibitors based on molecular simulation

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