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Introduction to Cancer, Conventional Therapies, and Bionano-Based Advanced Anticancer Strategies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Every tumor cell has an array of active surface molecules. Several of these molecules act as receptors for different ligands. These include cytokine receptors, human leukocyte antigens (HLAs), cell-adhesion molecules, and others. The expression of these receptors is a subject to modifications, typically to the advantage of tumors, supporting their growth and spread. Some receptors are completely new as they appear only on tumor cells, having no counterparts on normal cells. Tumor-cell receptors are critical in cancer research as they provide information that is important to create tools specific for tumor immunotherapy [104]. Drug delivery vehicle accumulation within targeted tissues can be enhanced via receptor-mediated targeting. Targeted drug delivery is essential for the enhanced tumor internalization. This occurs due to the interactions between ligand and receptor at the cell surface, rendering drug delivery vehicles to have a higher affinity for tissues affected with cancer and a lower affinity for the surrounding healthy tissue, as compared to non-targeted drugs. In this manner, receptor-mediated drug delivery can alter the bio-distribution of the drug by enhancing its accumulation in the tumor site [105].
Signal Transduction Mechanisms Regulating Cytokine-Mediated Induction of Acute Phase Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Several cytokine receptors function as multicomponent systems, consisting primarily of a binding component(s) and a signal transducing component(s). The binding subunit often represents the low-affinity receptor, which can interact with the signal transducing subunit, following ligand binding, to form the high-affinity receptor complex capable of initiating signal transduction. In the case of the IL-2 receptor, both subunits, α and β, individually bind IL-2 with low and intermediate affinities, respectively, whereas the αβ complex binds IL-2 with high affinity.
Identification Of Receptors In Vitro
Published in William C. Eckelman, Lelio G. Colombetti, Receptor-Binding Radiotracers, 2019
It is sometimes stated that a ligand should bind with high affinity for it to be a good candidate for binding to a pharmacologically relevant receptor. This is based on the observation that a number of drugs that act on one receptor at clinically relevant concentrations will also act on other receptors at higher concentrations (i.e., will bind to them with lower affinity). However, some agents normally act at much higher concentrations.
Da-Yuan-Yin decoction polyphenol fraction attenuates acute lung injury induced by lipopolysaccharide
Published in Pharmaceutical Biology, 2023
Lengqiu Guo, Yun Yang, Jie Yuan, Huiling Ren, Xiaolei Huang, Meng Li, Long Xia, Xiaogang Jiang, Daofeng Chen, Jian Zhang
The top ten target proteins with degree values were downloaded from the PDB database, and the AutoDock Vina software was used to calculate the minimum binding energy of the compound and target protein and drew a heat map. The affinity energy is a prerequisite indicator to determine whether the ligand small molecule can effectively bind to the receptor, with lower energy values suggesting the better binding capacity for the receptor and ligand. In this study, the lowest binding energy between the compounds and the top 10 target proteins with degree values was mostly less than −5 kal/mol, indicating that they could bind well. PyMoL was used to visualize the molecular docking results (Figure 11). The target protein was closely bound to the active component by hydrogen bond, aromatic interaction and other energetic molecular interactions, further demonstrating that the active component and target protein could form a relatively stable conformation and thus combine well.
Hawthorn leaves flavonoids attenuate cardiac remodeling induced by simulated microgravity
Published in Pharmaceutical Biology, 2023
Tian Liu, Yuqi Ma, Hui Zhao, Pengli Wang, Yan Niu, Yuehuan Hu, Xi Shen, Mingxia Zhang, Bing Yan, Jun Yu
Five major flavonoid compounds of HLF were unambiguously identified as vitexin-4″-O-glucoside, vitexin-2″-O-rhamnoside, vitexin, rutin, and hyperoside (Figure 5). The accuracy of docking between target proteins NPRA, PDE5A, PKG, and NFATc1 (PDB ID code: 1jdn, 3bjc, 4r4l and 5sve, respectively) and the five major HLF compounds was assessed. Lower binding energy was associated with better interaction between the receptor and ligand. Molecular docking of the compounds with PKG and NFATc1 exhibited strong interaction between the compounds with proteins (Table 1). With PKG, vitexin and hyperoside exhibited H-bonding interactions, carbon-hydrogen bonds and van der Waals to combine (Figure 6(C,D)). With NFATc1, vitexin-4″-O-glucoside, vitexin-2″-O-rhamnoside, vitexin, and hyperoside exhibited H-bonding interaction, pi-Alkyl and van der Waals to combine (Figure 6(E,H)). The results successfully predicted the binding ability of major components of HLF and target proteins. Therefore, PKG and NFATc1 were demonstrated to be targets of HLF.
Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1G2032R and ALKG1202R
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Siming Liu, Chuan Huang, Chunhui Huang, Yaqi Huang, Yonghuan Yu, Guowu Wu, Fengqiu Guo, Ying Jiang, Shanhe Wan, Zhengguang Zhu, Yuanxin Tian, Jianghua Zhu, Jiajie Zhang
Additionally, the binding-free energies of C01 and Crizotinib were also calculated by using MM-PBSA (molecular mechanics Poisson–Boltzmann surface area) and MM-GBSA (molecular mechanics Generalized-Born surface area) programs in AMBER. As Table S1 shown, MM-PBSA and MM-GBSA calculations demonstrated that C01 showed lower ΔGbind when interacting with ROS1-G2032R mutant compared to Crizotinib, which were in good agreement with the biological data. According to the energy individual components of the binding-free energies, the favourable contributors to ligand binding were van der Waals (vdW) terms, electrostatic and polar solvation energies, whereas nonpolar salvation and entropy terms oppose binding. The ΔGprep (GB) and ΔGprep (PB) also indicated that C01 could bind with ROS1-G2032R mutant more strongly, which was consistent with experimental data.