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Medicinal Research Reviews

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https://www.readbyqxmd.com/read/29323726/computational-chemical-biology-and-drug-design-facilitating-protein-structure-function-and-modulation-studies
#1
REVIEW
Mingyue Zheng, Jihui Zhao, Chen Cui, Zunyun Fu, Xutong Li, Xiaohong Liu, Xiaoyu Ding, Xiaoqin Tan, Fei Li, Xiaomin Luo, Kaixian Chen, Hualiang Jiang
Over the past quarter of a century, there has been rapid development in structural biology, which now can provide solid evidence for understanding the functions of proteins. Concurrently, computational approaches with particular relevance to the chemical biology and drug design (CBDD) field have also incrementally and steadily improved. Today, these methods help elucidate detailed working mechanisms and accelerate the discovery of new chemical modulators of proteins. In recent years, integrating computational simulations and predictions with experimental validation has allowed for more effective explorations of the structure, function and modulation of important therapeutic targets...
January 11, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29315702/strategies-to-target-the-hedgehog-signaling-pathway-for-cancer-therapy
#2
REVIEW
Minhang Xin, Xinyue Ji, Ladie Kimberly De La Cruz, Suresh Thareja, Binghe Wang
Hedgehog (Hh) signaling is an essential pathway in the human body, and plays a major role in embryo development and tissue patterning. Constitutive activation of the Hh signaling pathway through sporadic mutations or other mechanisms is explicitly associated with cancer development and progression in various solid malignancies. Therefore, targeted inhibition of the Hh signaling pathway has emerged as an attractive and validated therapeutic strategy for the treatment of a wide range of cancers. Vismodegib, a first-in-class Hh signaling pathway inhibitor was approved by the US Food and Drug Administration in 2012, and sonidegib, another potent Hh pathway inhibitor, received FDA's approval in 2015 as a new treatment of locally advanced or metastatic basal cell carcinoma...
January 5, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29315692/comprehensive-review-of-cardiovascular-toxicity-of-drugs-and-related-agents
#3
REVIEW
Přemysl Mladěnka, Lenka Applová, Jiří Patočka, Vera Marisa Costa, Fernando Remiao, Jana Pourová, Aleš Mladěnka, Jana Karlíčková, Luděk Jahodář, Marie Vopršalová, Kurt J Varner, Martin Štěrba
Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. The compounds are classified into agents that have significant effects on the heart, blood vessels, or both. The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases...
January 5, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29315675/chemical-modifications-of-nucleic-acid-drugs-and-their-delivery-systems-for-gene-based-therapy
#4
REVIEW
Changmai Chen, Zhenjun Yang, Xinjing Tang
Gene-based therapy is one of essential therapeutic strategies for precision medicine through targeting specific genes in specific cells of target tissues. However, there still exist many problems that need to be solved, such as safety, stability, selectivity, delivery, as well as immunity. Currently, the key challenges of gene-based therapy for clinical potential applications are the safe and effective nucleic acid drugs as well as their safe and efficient gene delivery systems. In this review, we first focus on current nucleic acid drugs and their formulation in clinical trials and on the market, including antisense oligonucleotide, siRNA, aptamer, and plasmid nucleic acid drugs...
January 5, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29283446/potential-cardiac-risk-of-immune-checkpoint-blockade-as-anticancer-treatment-what-we-know-what-we-do-not-know-and-what-we-can-do-to-prevent-adverse-effects
#5
REVIEW
Paolo Spallarossa, Giovanni Meliota, Claudio Brunelli, Eleonora Arboscello, Pietro Ameri, Christian Cadeddu Dessalvi, Francesco Grossi, Martino Deidda, Donato Mele, Matteo Sarocchi, Andrea Bellodi, Rosalinda Madonna, Giuseppe Mercuro
Cancer immunotherapy has become a well-established treatment option for some cancers after the development of a family of drugs targeting the so-called immune checkpoints, such as CTLA4 and PD-1 with PD-L1. These co-receptors/ligands inhibit the activation of T-cell, thus preventing an excessive inflammatory response. Tumors exploit these pathways to induce immune tolerance to themselves. Thus, the main effect of checkpoint-blocking drugs is to awake an immune response primarily directed against cancer cells...
December 28, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29283184/basic-understanding-and-therapeutic-approaches-to-target-toll-like-receptors-in-cancerous-microenvironment-and-metastasis
#6
REVIEW
Mojtaba Khajeh Alizadeh Attar, Muhammad Ayaz Anwar, Mahsa Eskian, Mahsa Keshavarz-Fathi, Sangdun Choi, Nima Rezaei
Toll-like receptors (TLRs) are transmembrane components that sense danger signals, like damage- and pathogen-associated molecular pattern molecules, as receptors, and maintain homeostasis in tissues. They are mainly involved in immune system activation through a variety of mediators, which either carry out (1) elimination of pathogenic threats and redressing homeostatic imbalances or (2) contribution to the initiation and worsening of pathological conditions, including cancers. Under physiological conditions, TLRs coordinate the innate and adaptive immunity, and inhibit autoimmune disorders...
December 28, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29278273/hypoxia-inducible-factor-1-hif-1-inhibitors-from-the-last-decade-2007-to-2016-a-structure-activity-relationship-perspective
#7
REVIEW
Deepak Bhattarai, Xuezhen Xu, Kyeong Lee
Tumor hypoxia is a common feature in most solid tumors and is associated with overexpression of the hypoxia response pathway. Overexpression of the hypoxia-inducible factor (HIF-1) protein leads to angiogenesis, metastasis, apoptosis resistance, and many other pro-tumorigenic responses in cancer development. HIF-1 is a promising target in cancer drug development to increase the patient's response to chemotherapy and radiotherapy as well as the survival rate of cancer patients. Since up to 1% of genes are hypoxia-sensitive, a target-specific HIF-1 inhibitor may be a better clinical candidate in cancer drug discovery...
December 26, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29149530/proteases-and-protease-inhibitors-in-infectious-diseases
#8
REVIEW
Ayodeji A Agbowuro, Wilhelmina M Huston, Allan B Gamble, Joel D A Tyndall
There are numerous proteases of pathogenic organisms that are currently targeted for therapeutic intervention along with many that are seen as potential drug targets. This review discusses the chemical and biological makeup of some key druggable proteases expressed by the five major classes of disease causing agents, namely bacteria, viruses, fungi, eukaryotes, and prions. While a few of these enzymes including HIV protease and HCV NS3-4A protease have been targeted to a clinically useful level, a number are yet to yield any clinical outcomes in terms of antimicrobial therapy...
November 17, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29095519/no-and-hno-donors-nitrones-and-nitroxides-past-present-and-future
#9
REVIEW
Catarina Oliveira, Sofia Benfeito, Carlos Fernandes, Fernando Cagide, Tiago Silva, Fernanda Borges
The biological effects attributed to nitric oxide ((•) NO) and nitroxyl (HNO) have been extensively studied, propelling their array of putative clinical applications beyond cardiovascular disorders toward other age-related diseases, like cancer and neurodegenerative diseases. In this context, the unique properties and reactivity of the N-O bond enabled the development of several classes of compounds with potential clinical interest, among which (•) NO and HNO donors, nitrones, and nitroxides are of particular importance...
November 2, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29064108/strategies-to-diversify-natural-products-for-drug-discovery
#10
REVIEW
Gang Li, Hong-Xiang Lou
Natural product libraries contain specialized metabolites derived from plants, animals, and microorganisms that play a pivotal role in drug discovery due to their immense structural diversity and wide variety of biological activities. The strategies to greatly extend natural product scaffolds through available biological and chemical approaches offer unique opportunities to access a new series of natural product analogues, enabling the construction of diverse natural product-like libraries. The affordability of these structurally diverse molecules has been a crucial step in accelerating drug discovery...
October 24, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28834581/pyrrolo-2-3-d-pyrimidine-7-deazapurine-as-a-privileged-scaffold-in-design-of-antitumor-and-antiviral-nucleosides
#11
REVIEW
Pavla Perlíková, Michal Hocek
7-Deazapurine (pyrrolo[2,3-d]pyrimidine) nucleosides are important analogues of biogenic purine nucleosides with diverse biological activities. Replacement of the N7 atom with a carbon atom makes the five-membered ring more electron rich and brings a possibility of attaching additional substituents at the C7 position. This often leads to derivatives with increased base-pairing in DNA or RNA or better binding to enzymes. Several types of 7-deazapurine nucleosides with potent cytostatic or cytotoxic effects have been identified...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28759124/recent-advances-in-uveal-melanoma-treatment
#12
REVIEW
Beatriz Álvarez-Rodríguez, Alfonso Latorre, Christian Posch, Álvaro Somoza
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Recent advances in the understanding of molecular characteristics helped to determine which tumors are most likely to progress. About 50% of patients carrying genetic alterations such as chromosomal aberrations and mutations are at significant risk for metastatic disease of which the majority will succumb to UM within few months. Currently, there is no effective treatment for metastatic uveal melanoma, and we hope this review will encourage researchers and clinicians to work to find a better standard of care...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28759115/anti-muc1-aptamer-a-potential-opportunity-for-cancer-treatment
#13
REVIEW
Maryam Sadat Nabavinia, Aida Gholoobi, Fahimeh Charbgoo, Mahboobeh Nabavinia, Mohammad Ramezani, Khalil Abnous
Mucin 1 (MUC1) is a protein usually found on the apical surface of most normal secretory epithelial cells. However, in most adenocarcinomas, MUC1 is overexpressed, so that it not only appears over the entire cell surface, but is also shed as MUC1 fragments into the blood stream. These phenomena pinpoint MUC1 as a potential target for the diagnosis and treatment of cancer; consequently, interest has increased in MUC1 as a molecular target for overcoming cancer therapy challenges. MUC1 currently ranks second among 75 antigen candidates for cancer vaccines, and different antibodies or aptamers against MUC1 protein are proving useful for tracing cancer cells in the emerging field of targeted delivery...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28682452/mitochondrial-dysfunction-and-potential-anticancer-therapy
#14
REVIEW
Matilde E Lleonart, Robert Grodzicki, Dmitri M Graifer, Alex Lyakhovich
Mitochondrial dysfunction (MDF) has been identified as an important factor in various diseases ranging from neurological disorders, to diseases of the cardiovascular system and metabolic syndromes. MDF was also found in cancer as well as in cancer predisposition syndromes with defective DNA damage response (DDR) machinery. Moreover, a recent highlight arises from the detection of MDF in eukaryotic cells upon treatment with antibiotics. In this review, we focus on recent studies of MDF in pathological conditions with a particular emphasis on the effects of various classes of antibiotics on mitochondria...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28643862/tumor-angiogenesis-revisited-regulators-and-clinical-implications
#15
REVIEW
Roberto Ronca, Mohammed Benkheil, Stefania Mitola, Sofie Struyf, Sandra Liekens
Since Judah Folkman hypothesized in 1971 that angiogenesis is required for solid tumor growth, numerous studies have been conducted to unravel the angiogenesis process, analyze its role in primary tumor growth, metastasis and angiogenic diseases, and to develop inhibitors of proangiogenic factors. These studies have led in 2004 to the approval of the first antiangiogenic agent (bevacizumab, a humanized antibody targeting vascular endothelial growth factor) for the treatment of patients with metastatic colorectal cancer...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28643446/artemisinin-as-an-anticancer-drug-recent-advances-in-target-profiling-and-mechanisms-of-action
#16
REVIEW
Yin Kwan Wong, Chengchao Xu, Karunakaran A Kalesh, Yingke He, Qingsong Lin, W S Fred Wong, Han-Ming Shen, Jigang Wang
Artemisinin and its derivatives (collectively termed as artemisinins) are among the most important and effective antimalarial drugs, with proven safety and efficacy in clinical use. Beyond their antimalarial effects, artemisinins have also been shown to possess selective anticancer properties, demonstrating cytotoxic effects against a wide range of cancer types both in vitro and in vivo. These effects appear to be mediated by artemisinin-induced changes in multiple signaling pathways, interfering simultaneously with multiple hallmarks of cancer...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28586525/novel-therapeutic-clues-in-thyroid-carcinomas-the-role-of-targeting-cancer-stem-cells
#17
REVIEW
Alessandro Antonelli, Concettina La Motta
Thyroid carcinomas (TCs), the most common endocrine tumors, represent the eighth most common cancer diagnosed worldwide in both women and men. To treat these malignancies, several drugs are now available and a number of novel ones have been enrolling in clinical trials, addressing both oncogenic pathways in cancer cells and angiogenic pathways in tumor endothelial cells. However, their use is not devoid of serious toxicities and their efficacy is limited, being dependent on carcinoma typology and the occurrence of acquired resistance...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28586517/extracellular-vesicles-in-the-tumor-microenvironment-therapeutic-resistance-clinical-biomarkers-and-targeting-strategies
#18
REVIEW
L Han, J Xu, Q Xu, B Zhang, E W-F Lam, Y Sun
Numerous studies have proved that cell-nonautonomous regulation of neoplastic cells is a distinctive and essential characteristic of tumorigenesis. Two way communications between the tumor and the stroma, or within the tumor significantly influence disease progression and modify treatment responses. In the tumor microenvironment (TME), malignant cells utilize paracrine signaling initiated by adjacent stromal cells to acquire resistance against multiple types of anticancer therapies, wherein extracellular vesicles (EVs) substantially promote such events...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28510338/therapeutic-targeting-of-poly-adp-ribose-polymerase-1-parp1-in-cancer-current-developments-therapeutic-strategies-and-future-opportunities
#19
REVIEW
Jyotika Rajawat, Nidhi Shukla, Durga Prasad Mishra
Poly(ADP-ribose) polymerase-1 (PARP-1) plays a central role in numerous cellular processes including DNA repair, replication, and transcription. PARP interacts directly, indirectly or via PARylation with various oncogenic proteins and regulates several transcription factors thereby modulating carcinogenesis. Therapeutic inhibition of PARP is therefore perceived as a promising anticancer strategy and a number of PARP inhibitors (PARPi) are currently under development and clinical evaluation. PARPi inhibit the DNA repair pathway and thus form the concept of synthetic lethality in cancer therapeutics...
November 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28181261/the-search-for-potent-small-molecule-hdacis-in-cancer-treatment-a-decade-after-vorinostat
#20
REVIEW
Chiara Zagni, Giuseppe Floresta, Giulia Monciino, Antonio Rescifina
Histone deacetylases (HDACs) play a crucial role in the remodeling of chromatin, and are involved in the epigenetic regulation of gene expression. In the last decade, inhibition of HDACs came out as a target for specific epigenetic changes associated with cancer and other diseases. Until now, more than 20 HDAC inhibitors (HDACIs) have entered clinical studies, and some of them (e.g., vorinostat, romidepsin) have been approved for the treatment of cutaneous T-cell lymphoma. This review provides an overview of current knowledge, progress, and molecular mechanisms of HDACIs, covering a period from 2011 until 2015...
November 2017: Medicinal Research Reviews
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