Related Experiment Video
Updated: Jul 12, 2025
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
In silico design and cell-based evaluation of two dual anti breast cancer compounds targeting Bcl-2 and GPER
Loreley-A Morelos-Garnica1, Sonia Guzmán-Velázquez2, Itzia-I Padilla-Martínez3
1Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Alcaldía Miguel Hidalgo, C.P. 11340, Mexico City, México.
Abstract:
According to WHO statistics, breast cancer (BC) disease represents about 2.3 million diagnosed and 685,000 deaths globally. Regarding histological classification of BC, the Estrogen (ER) and Progesterone (PR) receptors negative-expression cancer, named Triple-Negative BC (TNBC), represents the most aggressive type of this disease, making it a challenge for drug discovery. In this context, our research group, applying a well-established Virtual Screening (VS) protocol, in addition to docking and molecular dynamics simulations studies, yielded two ligands identified as 6 and 37 which were chemically synthesized and evaluated on MCF-7 and MDA-MB-231 cancer cell lines. Strikingly, 37 assayed on MDA-MB-231 (a TNBC cell model) depicted an outstanding value of 18.66 μM much lower than 65.67 μM yielded by Gossypol Bcl-2 inhibitor whose main disadvantage is to produce multiple toxic effects. Highlighted above, enforce the premise of the computational tools to find new therapeutic options against the most aggressive forms of breast cancer, as the results herein showed.
Insights
Computational methods identified a promising new compound, ligand 37, for treating aggressive Triple-Negative Breast Cancer (TNBC). This discovery offers a potentially less toxic alternative to existing treatments for breast cancer patients.
Area of Science:
- Oncology
- Computational Chemistry
- Drug Discovery
Background:
- Breast cancer (BC) is a global health concern, with over 2.3 million diagnoses and 685,000 deaths annually.
- Triple-Negative Breast Cancer (TNBC), characterized by Estrogen and Progesterone receptor negativity, is particularly aggressive and challenging for drug development.
- Existing treatments like Gossypol for TNBC can have significant toxic side effects.
Purpose of the Study:
- To leverage computational tools for identifying novel therapeutic agents against aggressive breast cancer subtypes.
- To discover and synthesize potential drug candidates with improved efficacy and reduced toxicity compared to current options.
- To evaluate the efficacy of novel compounds in preclinical cancer models.
Main Methods:
- Utilized Virtual Screening (VS) protocols to identify potential drug candidates.
- Performed molecular docking and dynamics simulations to assess ligand-target interactions.
- Synthesized two identified ligands (6 and 37) and evaluated their activity on breast cancer cell lines (MCF-7 and MDA-MB-231).
Main Results:
- Ligand 37 demonstrated significant efficacy against the MDA-MB-231 TNBC cell line with an IC50 of 18.66 μM.
- This potency is notably superior to Gossypol (65.67 μM), a known Bcl-2 inhibitor.
- Ligand 37 shows potential as a targeted therapy with fewer toxic effects.
Conclusions:
- Computational approaches are effective in discovering novel therapeutic compounds for challenging cancers like TNBC.
- Ligand 37 represents a promising candidate for further development as a breast cancer therapeutic.
- This research highlights the potential of in silico methods to accelerate the discovery of safer and more effective cancer drugs.
More Related Videos
07:48Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
Published on: December 26, 2016
13:34A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
Published on: April 6, 2016
