Molecular Docking and Pharmacokinetic Profiling of Nab-paclitaxel as Advanced Chemotherapeutic Agent Against HER-2 Positive Breast Cancer Patients

Mangilit, Nicole Jacob DJ; Arkoncel, Ana Beatrice S.; Baylon, Karyll Mikaela DL.; Eslabra, Jan Marnylle V.; De Borja, John Lawrence D.; Nakama, Johji G.; Esmalla, Maria Salvacion A.; Labrador, Alexis M.; Paulin, John P.; Santiago-Bautista, Myla R.

doi:10.31557/APJCP.2024.25.10.3447

Molecular Docking and Pharmacokinetic Profiling of Nab-paclitaxel as Advanced Chemotherapeutic Agent Against HER-2 Positive Breast Cancer Patients

Document Type : Research Articles

Authors

¹ Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines.

² Research Center for the Natural and Applied Sciences, University of Santo Tomas, Manila, Philippines.

10.31557/APJCP.2024.25.10.3447

Abstract

Objective: The main objective of the study is to explore the potential molecular benefits of Nab-paclitaxel as an effective advanced chemotherapeutic agent for HER2-positive breast cancer patients. Specifically, the study aims to assess Nab-paclitaxel as a potential drug candidate for breast cancer treatment. Methods: This study used bioinformatics and cheminformatics to analyze the HER2 signaling pathway and its possible interactions with Nab-Paclitaxel. This involves using pharmacokinetic profiling software to evaluate its physicochemical properties, analyzing its potential impact on gene expression modulation, and assessing its binding affinity to the HER2 receptor through molecular docking. Result: The results indicate that the most favorable docking pose occurs between chain B of the HER-2 receptor and Paclitaxel, with a binding energy of -9.4 kcal/mol. Notably, a hydrogen bond is observed in ARG849, with 3.0 Angstrom (Å). Previous research highlights Paclitaxel’s impact on breast cancer patients’ genes, particularly the ABCB1 gene responsible for P-glycoprotein production, contributing to drug resistance in chemotherapy. Nab-paclitaxel exhibits potential ease of metabolism, as it minimally inhibits drug-metabolizing cytochrome P450 enzymes. Additionally, despite initial concerns related to drug-likeness parameters and molecular weight discrepancies, the pharmacokinetic profile of Nab-Paclitaxel suggests improvements in delivery facilitated by an albumin-supported nanoparticle delivery mechanism. Conclusion: The binding energy confirms the secure docking of ligands to receptors, suggesting the stability of the interaction between them. Nevertheless, prolonged administration of Paclitaxel poses the risk of inducing drug resistance, a significant factor contributing to treatment failure. This emphasizes the need to explore new candidate drug combinations or identify alternative drug-binding interaction sites. Such endeavors hold the potential to enhance the effectiveness of drug treatments and address challenges associated with prolonged Paclitaxel use.

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