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The Role of Natural Products in COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Iqra Akhtar, Sumera Javad, Tehreema Iftikhar, Amina Tariq, Hammad Majeed, Asma Ahmad, Muhammad Arfan, M. Zia-Ul-Haq
Molecular docking is a common and modern technique which is used now a day to discover new drug formulas. A number of software are in use for this purpose. This procedure can analyze small molecules for their interaction with the binding sites of target enzymes or proteins. The capacity of a molecule to bind with minimum energy is searched out. This binding of natural products and target proteins depend upon the shape of the molecule and electrostatic forces between them. Its’ such a successful method that it can be used for such target proteins whose structure is still undiscovered but can be done with some homologous structures as in the case of various proteins involved in SARS CoV and COVID-19 infections [61].
Nanomaterials in Chemotherapy
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
P. K. Hashim, Anjaneyulu Dirisala
A drug is defined as a natural or artificial pharmacologically active ingredient used for the detection, diagnosis, and treatment of a disease. A drug can be either hydrophobic (e.g., paclitaxel, cisplatin, and methotrexate) or hydrophilic (e.g., gemcitabine, L-asparaginase, and antibodies) depending on its aqueous solubility [1]. Also, a drug can be negatively charged (e.g., gene therapeutics such as DNA, messenger (m)RNA, and short interfering (si)RNA), positively charged (e.g., doxorubicin (DOX)), and neutral (e.g., cisplatin) based on the charged species present in the drug. A drug also can be a small molecule, which has a low molecular weight compound below 900 daltons (e.g., DOX and cisplatin), or a high molecular weight molecule (e.g., DNA, RNA, and proteins). The structural characteristics of drugs are often related to their functions. For instance, a small molecule drug usually binds to a target gene/protein as a first step in the complicated drug action mechanisms. Small molecule drugs often induce off-target adverse effects because of their lack of specificity. In contrast to small molecule drugs, macromolecule drugs (e.g., genes and proteins) typically bind to their target either expressed on the cell surface or intracellular component with high specificity, and correct or program the disease-causing elements. Advantageously, both small molecule- and macromolecule-drugs can be used for cancer therapy. Collectively, more than 150 anticancer drugs have been approved by the US Food and Drug Administration (FDA) for various types of cancer [2].
Introduction to dermatological treatment
Published in Richard Ashton, Barbara Leppard, Differential Diagnosis in Dermatology, 2021
Richard Ashton, Barbara Leppard
Many intracellular pathways driven by cytokine receptors depend on the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway. Some of these are involved in causing inflammatory dermatoses. Inhibiting this pathway using a JAK inhibitor may be beneficial in atopic eczema, alopecia areata, psoriasis and vitiligo. These are small molecules that can be taken orally or possibly applied topically. The first oral JAK-inhibitor (tofacitinib) has been approved for the treatment of psoriatic arthritis. In dermatology their future use will be increasingly important with the development of topical agents.
Design, synthesis, and biological evaluation of potent FAK-degrading PROTACs
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Qiaohua Qin, Ruifeng Wang, Qinglin Fu, Guoqi Zhang, Tianxiao Wu, Nian Liu, Ruicheng Lv, Wenbo Yin, Yin Sun, Yixiang Sun, Dongmei Zhao, Maosheng Cheng
To date, several potent FAK inhibitors have been developed, and some of them were conducted clinical evaluation. GSK-2256098, VS-4718, PF-562271 and Defactinib are ATP-competitive inhibitors of kinase domain. GSK-2256098 is a highly selective inhibitor of FAK and has been shown to efficiently inhibit the phosphorylation of Tyr39711. VS-4718 is used to treat metastatic non-hematological malignancies, advanced non-hematological malignancies or advanced pancreatic cancer of patients in combination with gemcitabine or nabutaxel12. PF-562271 is a highly active and highly selective FAK inhibitor developed by Pfizer13. Defactinib is evaluated to treat ovarian cancer, pancreatic cancer, non-small cell lung cancer and mesothelioma in combination with checkpoint inhibitors14. As we said above, FAK exerts kinase-dependent enzymatic functions and kinase-independent scaffolding functions. The development of the small-molecule inhibitors can inhibit the enzymatic functions of FAK, but can’t prevent the kinase-independent scaffolding functions. In addition, small molecule drugs are likely to cause off-target toxicity and even drug resistance at high concentrations. In summary, it is necessary to develop a strategy against both the enzymatic functions and scaffolding functions of FAK.
Rebellion of the deregulated regulators: What is the clinical relevance of studying intrinsically disordered proteins?
Published in Expert Review of Proteomics, 2022
For a long time, the field of small molecule drug discovery has persisted in using outdated strategies even after the concept of protein intrinsic disorder became widely known. For example, the development of oral drugs followed a useful guideline known as Lipinski’s rule of five [17], which is inseparable from the classic ‘lock-and-key’ concept. However, recent advances in deep learning algorithms have reshaped the processes of drug discovery and development not only by enhancing design of the small-molecule drugs, but also by enabling creation of the artificially designed peptides and proteins [18]. Furthermore, since nucleic acid aptamers are able to bind specifically to various targets [19], aptamers capable of interaction with the IDRs of target proteins can be found, thereby representing another promising approach to discover novel drugs for protein clouds.
Emerging drug targets for colon cancer: A preclinical assessment
Published in Expert Opinion on Therapeutic Targets, 2022
Madison M. Crutcher, Trevor R. Baybutt, Jessica S. Kopenhaver, Adam E. Snook, Scott A. Waldman
Drugs can alternatively be classified by size: small molecules and macromolecules. Small molecule drugs are compounds with a low molecular weight that enter cells and interact with the cytoplasmic domain of cell-surface receptors and intracellular signaling molecules. Small molecules have well-established development paradigms, are less expensive, and are more convenient to administer than macromolecules [4]. Macromolecules are typically biologics and include monoclonal antibodies, polypeptides, antibody-drug conjugates, and nucleic acids. For extracellular targets, such as cell surface receptors or membrane-bound sites on cancer cells, therapeutic antibodies often directly regulate downstream cell cycle progression and cell death. These larger molecules can only act on the cell surface or on secreted molecules due to their inability to pass through the cell membrane. In addition, certain monoclonal antibodies work on cells other than cancer cells, such as immune cells, to restore stalled antitumor immune responses [5]. The first targeted agent for CRC was cetuximab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR) that was approved by the FDA in 2004, with bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), approved later that year. While these relatively few available targeted drugs have impacted survival in CRC, additional targets and therapies need to be identified.