Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines.
Research Center for the Natural and Applied Sciences, University of Santo Tomas, Manila, Philippines.
Asian Pac J Cancer Prev. 2024 Oct 1;25(10):3447-3456. doi: 10.31557/APJCP.2024.25.10.3447.
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.
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.
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.
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.
本研究的主要目的是探索奈达铂作为曲妥珠单抗阳性乳腺癌患者有效化疗药物的潜在分子益处。具体而言，本研究旨在评估奈达铂作为乳腺癌治疗的潜在候选药物。
本研究使用生物信息学和化学信息学方法分析 HER2 信号通路及其与奈达铂的可能相互作用。这包括使用药代动力学分析软件评估其物理化学性质，分析其对基因表达调控的潜在影响，以及通过分子对接评估其与 HER2 受体的结合亲和力。
结果表明，HER-2 受体链 B 与紫杉醇之间的最有利对接构象，结合能为-9.4 kcal/mol。值得注意的是，在 ARG849 观察到氢键，距离为 3.0 埃（Å）。先前的研究强调了紫杉醇对乳腺癌患者基因的影响，特别是负责产生 P-糖蛋白的 ABCB1 基因，导致化疗耐药。奈达铂具有潜在的易代谢性，因为它对药物代谢细胞色素 P450 酶的抑制作用最小。此外，尽管最初存在与药物相似性参数和分子量差异相关的担忧，但奈达铂的药代动力学特征表明，白蛋白支持的纳米颗粒递送机制可改善药物递送。
结合能证实了配体与受体的稳定对接，表明它们之间相互作用的稳定性。然而，紫杉醇的长期给药会导致产生药物耐药性的风险，这是导致治疗失败的一个重要因素。这强调了需要探索新的候选药物组合或确定替代药物结合相互作用位点的必要性。这些努力有潜力提高药物治疗的效果，并解决与紫杉醇长期使用相关的挑战。
