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Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib
BCR-ABL1 is a fusion protein as a result of a unique chromosomal translocation (producing the so-called Philadelphia chromosome) that serves as a clinical biomarker primarily for chronic myeloid leukemia (CML); the Philadelphia chromosome also occurs, albeit rather rarely, in other types of leukemia...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135824/ https://www.ncbi.nlm.nih.gov/pubmed/37189659 http://dx.doi.org/10.3390/biomedicines11041041 |
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author | Naveed, Muhammad Ain, Noor ul Aziz, Tariq Javed, Khushbakht Shabbir, Muhammad Aqib Alharbi, Metab Alsahammari, Abdulrahman Alasmari, Abdullah F. |
author_facet | Naveed, Muhammad Ain, Noor ul Aziz, Tariq Javed, Khushbakht Shabbir, Muhammad Aqib Alharbi, Metab Alsahammari, Abdulrahman Alasmari, Abdullah F. |
author_sort | Naveed, Muhammad |
collection | PubMed |
description | BCR-ABL1 is a fusion protein as a result of a unique chromosomal translocation (producing the so-called Philadelphia chromosome) that serves as a clinical biomarker primarily for chronic myeloid leukemia (CML); the Philadelphia chromosome also occurs, albeit rather rarely, in other types of leukemia. This fusion protein has proven itself to be a promising therapeutic target. Exploiting the natural vitamin E molecule gamma-tocotrienol as a BCR-ABL1 inhibitor with deep learning artificial intelligence (AI) drug design, this study aims to overcome the present toxicity that embodies the currently provided medications for (Ph+) leukemia, especially asciminib. Gamma-tocotrienol was employed in an AI server for drug design to construct three effective de novo drug compounds for the BCR-ABL1 fusion protein. The AIGT’s (Artificial Intelligence Gamma-Tocotrienol) drug-likeliness analysis among the three led to its nomination as a target possibility. The toxicity assessment research comparing AIGT and asciminib demonstrates that AIGT, in addition to being more effective nonetheless, is also hepatoprotective. While almost all CML patients can achieve remission with tyrosine kinase inhibitors (such as asciminib), they are not cured in the strict sense. Hence it is important to develop new avenues to treat CML. We present in this study new formulations of AIGT. The docking of the AIGT with BCR-ABL1 exhibited a binding affinity of −7.486 kcal/mol, highlighting the AIGT’s feasibility as a pharmaceutical option. Since current medical care only exclusively cures a small number of patients of CML with utter toxicity as a pressing consequence, a new possibility to tackle adverse instances is therefore presented in this study by new formulations of natural compounds of vitamin E, gamma-tocotrienol, thoroughly designed by AI. Even though AI-designed AIGT is effective and adequately safe as computed, in vivo testing is mandatory for the verification of the in vitro results. |
format | Online Article Text |
id | pubmed-10135824 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101358242023-04-28 Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib Naveed, Muhammad Ain, Noor ul Aziz, Tariq Javed, Khushbakht Shabbir, Muhammad Aqib Alharbi, Metab Alsahammari, Abdulrahman Alasmari, Abdullah F. Biomedicines Article BCR-ABL1 is a fusion protein as a result of a unique chromosomal translocation (producing the so-called Philadelphia chromosome) that serves as a clinical biomarker primarily for chronic myeloid leukemia (CML); the Philadelphia chromosome also occurs, albeit rather rarely, in other types of leukemia. This fusion protein has proven itself to be a promising therapeutic target. Exploiting the natural vitamin E molecule gamma-tocotrienol as a BCR-ABL1 inhibitor with deep learning artificial intelligence (AI) drug design, this study aims to overcome the present toxicity that embodies the currently provided medications for (Ph+) leukemia, especially asciminib. Gamma-tocotrienol was employed in an AI server for drug design to construct three effective de novo drug compounds for the BCR-ABL1 fusion protein. The AIGT’s (Artificial Intelligence Gamma-Tocotrienol) drug-likeliness analysis among the three led to its nomination as a target possibility. The toxicity assessment research comparing AIGT and asciminib demonstrates that AIGT, in addition to being more effective nonetheless, is also hepatoprotective. While almost all CML patients can achieve remission with tyrosine kinase inhibitors (such as asciminib), they are not cured in the strict sense. Hence it is important to develop new avenues to treat CML. We present in this study new formulations of AIGT. The docking of the AIGT with BCR-ABL1 exhibited a binding affinity of −7.486 kcal/mol, highlighting the AIGT’s feasibility as a pharmaceutical option. Since current medical care only exclusively cures a small number of patients of CML with utter toxicity as a pressing consequence, a new possibility to tackle adverse instances is therefore presented in this study by new formulations of natural compounds of vitamin E, gamma-tocotrienol, thoroughly designed by AI. Even though AI-designed AIGT is effective and adequately safe as computed, in vivo testing is mandatory for the verification of the in vitro results. MDPI 2023-03-28 /pmc/articles/PMC10135824/ /pubmed/37189659 http://dx.doi.org/10.3390/biomedicines11041041 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Naveed, Muhammad Ain, Noor ul Aziz, Tariq Javed, Khushbakht Shabbir, Muhammad Aqib Alharbi, Metab Alsahammari, Abdulrahman Alasmari, Abdullah F. Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib |
title | Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib |
title_full | Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib |
title_fullStr | Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib |
title_full_unstemmed | Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib |
title_short | Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib |
title_sort | artificial intelligence assisted pharmacophore design for philadelphia chromosome-positive leukemia with gamma-tocotrienol: a toxicity comparison approach with asciminib |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135824/ https://www.ncbi.nlm.nih.gov/pubmed/37189659 http://dx.doi.org/10.3390/biomedicines11041041 |
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