Your browser doesn't support javascript.
loading
Lumacaftor as a potential repurposed drug in targeting breast cancer stem cells: insights from in silico study.
Pathak, Yamini; Camps, Ihosvany; Yadav, Manju; Mishra, Amaresh; Upadhyay, Jyoti; Tripathi, Vishwas.
Afiliación
  • Pathak Y; School of Biotechnology, Gautam Buddha University, Greater Noida, 201310, India.
  • Camps I; Laboratório de Modelagem Computacional - LaModel, Instituto de Ciências Exatas - ICEx. Universidade Federal de Alfenas - UNIFAL-MG, Alfenas, Minas Gerais, Brazil.
  • Yadav M; High Performance & Quantum Computing Labs, Waterloo, Canada.
  • Mishra A; Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, India.
  • Upadhyay J; School of Biotechnology, Gautam Buddha University, Greater Noida, 201310, India.
  • Tripathi V; School of Biotechnology, Gautam Buddha University, Greater Noida, 201310, India.
J Mol Model ; 30(7): 227, 2024 Jun 24.
Article en En | MEDLINE | ID: mdl-38913211
ABSTRACT
CONTEXT Breast cancer stem cells (BCSCs) are a small subset of cells within breast tumors with characteristics similar to normal stem cells. Despite advancements in chemotherapy and targeted therapy for breast cancer, the prognosis for breast cancer patients has remained poor due to drug resistance, reoccurrence, and metastasis. Growing evidence suggests that deregulation of the self-renewal pathways, like the Wnt signaling pathway mediated by ß-catenin, plays a crucial role in the survival of breast cancer stem cells. Targeting the Wnt signaling pathway in breast cancer stem cells offers a promising avenue for developing effective therapeutic strategies targeting these cells, potentially leading to improved patient outcomes and reduced tumor recurrence.

METHODS:

For this purpose, we have screened a 1615 FDA-approved drug library against our target protein, ß-catenin, which is involved in the Wnt signaling pathway using molecular docking analysis, molecular dynamics (MD) simulations, and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations.

RESULTS:

Molecular docking studies showed that the Lumacaftor- ß-catenin complex had the lowest docking score of - 8.7 kcal/mol towards ß-catenin protein than the reference inhibitor. Molecular dynamic simulations and MM/PBSA calculations were also performed for the Lumacaftor-ß-catenin complex to establish the stability of the interactions involved. Considering its promising attributes and encouraging results, Lumacaftor holds significant potential as a novel therapeutic option to target BCSCs. This study opens avenues for further investigation and may pave the way for developing therapeutic potential in breast cancer treatment. Further confirmation is warranted through in vitro and clinical studies to validate the findings of this study.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Neoplasias de la Mama / Benzodioxoles / Beta Catenina / Simulación de Dinámica Molecular / Reposicionamiento de Medicamentos / Vía de Señalización Wnt / Simulación del Acoplamiento Molecular Límite: Female / Humans Idioma: En Revista: J Mol Model Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Neoplasias de la Mama / Benzodioxoles / Beta Catenina / Simulación de Dinámica Molecular / Reposicionamiento de Medicamentos / Vía de Señalización Wnt / Simulación del Acoplamiento Molecular Límite: Female / Humans Idioma: En Revista: J Mol Model Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Alemania