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Medicinal Research Reviews

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https://www.readbyqxmd.com/read/30004586/protein-protein-interactions-as-antibiotic-targets-a-medicinal-chemistry-perspective
#1
REVIEW
Peter J Cossar, Peter J Lewis, Adam McCluskey
There are 27 small molecule protein-protein interaction (PPI) modulators in Phase I, II, and III clinical trials targeting cancer, viruses, autoimmune disorders, and as immune suppression agents. Targeting PPIs as an antibiotic drug discovery strategy remains in relative infancy by comparison. However, a number of molecules are in development which target PPI within the replisome, divisome, transcriptome, and translatome are showing significant promise at the medicinal chemistry stage of drug development. Hence, the success of future PPI agents as antibiotics will build upon the techniques and design strategies of these molecules...
July 13, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29949198/death-associated-protein-kinase-dapk-family-modulators-current-and-future-therapeutic-outcomes
#2
REVIEW
Ahmed Karam Farag, Eun Joo Roh
Serine/threonine kinases (STKs) represent the majority of discovered kinases to date even though a few Food and Drug Administration approved STKs inhibitors are reported. The third millennium came with the discovery of an important group of STKs that reshaped our understanding of several biological signaling pathways. This family was named death-associated protein kinase family (DAPK family). DAPKs comprise five members (DAPK1, DAPK2, DAPK3, DRAK1, and DRAK2) and belong to the calcium/calmodulin-dependent kinases domain...
June 27, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29878411/new-strategies-in-achieving-antiangiogenic-effect-multiplex-inhibitors-suppressing-compensatory-activations-of-rtks
#3
REVIEW
Yuanyuan Shan, Binghe Wang, Jie Zhang
Pathological angiogenesis plays a crucial role in malignant neoplasia. Vascular normalization has been confirmed as a promising strategy to promote chemotherapy efficacy. However, compensatory activation of alternative angiogenic receptor tyrosine kinases (RTKs) reduces vascular normalization and induces resistance. Moreover, complexity and heterogeneity of angiogenesis make it difficult to treat with single-target agents. Accordingly, it has been proposed that multiplex inhibition of RTKs could enhance treatment efficacy and overcome resistance on the basis of the vascular normalization concept...
June 7, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29855050/complex-roles-of-the-old-drug-aspirin-in-cancer-chemoprevention-and-therapy
#4
REVIEW
Hui Hua, Hongying Zhang, Qingbin Kong, Jiao Wang, Yangfu Jiang
The nonsteroidal anti-inflammatory agent aspirin is widely used for preventing and treating cardiovascular and cerebrovascular diseases. In addition, epidemiologic evidences reveal that aspirin may prevent a variety of human cancers, while data on the association between aspirin and some kinds of cancer are conflicting. Preclinical studies and clinical trials also reveal the therapeutic effect of aspirin on cancer. Although cyclooxygenase is a well-known target of aspirin, recent studies uncover other targets of aspirin and its metabolites, such as AMP-activated protein kinase, cyclin-dependent kinase, heparanase, and histone...
June 1, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29846950/selective-targeting-of-antiapoptotic-bcl-2-proteins-in-cancer
#5
REVIEW
Ahmet Can Timucin, Huveyda Basaga, Ozgur Kutuk
Circumvention of apoptotic machinery is one of the distinctive properties of carcinogenesis. Extensively established key effectors of such apoptotic bypass mechanisms, the antiapoptotic BCL-2 (apoptosis regulator BCL-2) proteins, determine the response of cancer cells to chemotherapeutics. Within this background, research and development of antiapoptotic BCL-2 inhibitors were considered to have a tremendous amount of potential toward the discovery of novel pharmacological modulators in cancer. In this review, milestone achievements in the development of selective antiapoptotic BCL-2 proteins inhibitors for BCL-2, BCL-XL (BCL-2-like protein 1), and MCL-1 (induced myeloid leukemia cell differentiation protein MCL-1) were summarized and their future implications were discussed...
May 30, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29846948/chitosan-based-multifunctional-nanomedicines-and-theranostics-for-targeted-therapy-of-cancer
#6
REVIEW
Marziyeh Fathi, Sima Majidi, Parham Sahandi Zangabad, Jaleh Barar, Hamid Erfan-Niya, Yadollah Omidi
Nanotechnology as an emerging field has established inevitable impacts on nano-biomedicine and treatment of formidable diseases, inflammations, and malignancies. In this regard, substantial advances in the design of systems for delivery of therapeutic agents have emerged magnificent and innovative pathways in biomedical applications. Chitosan (CS) is derived via deacetylation of chitin as the second most abundant polysaccharide. Owing to the unique properties of CS (e.g., biocompatibility, biodegradability, bioactivity, mucoadhesion, cationic nature and functional groups), it is an excellent candidate for diverse biomedical and pharmaceutical applications such as drug/gene delivery, transplantation of encapsulated cells, tissue engineering, wound healing, antimicrobial purposes, etc...
May 30, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29846945/progress-and-challenges-in-the-prevention-and-control-of-nonalcoholic-fatty-liver-disease
#7
REVIEW
Jingjing Cai, Xiao-Jing Zhang, Hongliang Li
Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. Individuals with NAFLD have a high frequency of developing progressive liver disease and metabolism-related comorbidities, which result from of a lack of awareness and poor surveillance of the disease and a paucity of approved and effective therapies. Managing the complications of NAFLD has already begun to place a tremendous burden on health-care systems. Although efforts to identify effective therapies are underway, the lack of validated preclinical NAFLD models that represent the biology and outcomes of human disease remains a major barrier...
May 30, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29809286/small-molecule-inhibitors-of-multidrug-resistance-associated-protein-1-and-related-processes-a-historic-approach-and-recent-advances
#8
REVIEW
Sven Marcel Stefan, Michael Wiese
Multidrug resistance-associated protein 1 (MRP1, ABCC1) is an ATP-binding cassette (ABC) transport protein. This efflux pump uses the energy of ATP hydrolysis to export structurally diverse antineoplastic agents in human cancers. The upregulation of MRP1 (either inherent or acquired) is one major reason for the occurrence of the phenomenon called multidrug resistance (MDR). MDR is characterized by a reduced outcome of chemotherapy due to the active intracellular clearance of cytostatic drugs below the necessary effect concentration...
May 29, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29806214/mechanisms-and-pathways-of-anti-inflammatory-activity-of-dpp-4-inhibitors-in-cardiovascular-and-renal-protection
#9
REVIEW
Katarina Tomovic, Jelena Lazarevic, Gordana Kocic, Marina Deljanin-Ilic, Marko Anderluh, Andrija Smelcerovic
Dipeptidyl peptidase-4 (DPP-4) cleaves N-terminal dipeptides, with Pro, Ala or Ser at the penultimate position, and, in that way, modulates biological activity of certain polypeptides. Due to its ubiquitous distribution, many pathological processes are associated with altered DPP-4 expression and activity. Besides the regulation of glucose metabolism, DPP-4 also exhibits many other systemic effects, and the inhibition of its activity might lead to cardiovascular and renal protection. Mechanisms underlying these protective effects of DPP-4 inhibition are ascribed to elevated bioavailability of its substrates, to impacts on mediators and signaling pathways that ameliorate cardiovascular and renal function through the suppression of oxidative stress, inflammation, fibrosis and apoptosis, improved endothelial function and tissue reparation...
May 28, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29785841/effects-of-antipsychotic-drugs-on-neurites-relevant-to-schizophrenia-treatment
#10
REVIEW
Xu-Feng Huang, Xueqin Song
Although antipsychotic drugs are mainly used for treating schizophrenia, they are widely used for treating various psychiatric diseases in adults, the elderly, adolescents and even children. Today, about 1.2% of the worldwide population suffers from psychosis and related disorders, which translates to about 7.5 million subjects potentially targeted by antipsychotic drugs. Neurites project from the cell body of neurons and connect neurons to each other to form neural networks. Deficits in neurite outgrowth and integrity are implicated in psychiatric diseases including schizophrenia...
May 22, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29785785/metabolism-within-the-tumor-microenvironment-and-its-implication-on-cancer-progression-an-ongoing-therapeutic-target
#11
REVIEW
Ma Carmen Ocaña, Beatriz Martínez-Poveda, Ana R Quesada, Miguel Ángel Medina
Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment (TME)...
May 22, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29771460/targeting-prostate-cancer-prostate-specific-membrane-antigen-based-diagnosis-and-therapy
#12
REVIEW
Till Wüstemann, Uwe Haberkorn, John Babich, Walter Mier
The high incidence rates of prostate cancer (PCa) raise demand for improved therapeutic strategies. Prostate tumors specifically express the prostate-specific membrane antigen (PSMA), a membrane-bound protease. As PSMA is highly overexpressed on malignant prostate tumor cells and as its expression rate correlates with the aggressiveness of the disease, this tumor-associated biomarker provides the possibility to develop new strategies for diagnostics and therapy of PCa. Major advances have been made in PSMA targeting, ranging from immunotherapeutic approaches to therapeutic small molecules...
May 17, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29766541/gold-nanoparticles-in-ophthalmology
#13
REVIEW
Florence Masse, Mathieu Ouellette, Guillaume Lamoureux, Elodie Boisselier
Many research projects are underway to improve the diagnosis and therapy in ophthalmology. Indeed, visual acuity deficits affect 285 million people worldwide and different strategies are being developed to strengthen patient care. One of these strategies is the use of gold nanoparticles (GNP) for their multiple properties and their ability to be used as both diagnosis and therapy tools. This review exhaustively details research developing GNPs for use in ophthalmology. The toxicity of GNPs and their distribution in the eye are described through in vitro and in vivo studies...
May 16, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29733451/the-underlying-pathophysiology-and-therapeutic-approaches-for-osteoporosis
#14
REVIEW
Harshika Awasthi, Dayanandan Mani, Divya Singh, Atul Gupta
With an increase in the ageing population worldwide, the prevalence of osteoporosis increases at an alarming rate in both male and female irrespective of their ethnicity. At present, the currently available therapeutic options are mostly limited to either bone resorptive or bone forming efficacies and both approaches are associated with serious side effects. Despite these options, there is still need for newer therapeutics to treat osteoporosis, which can offer beneficial effects for maintaining balanced dynamics between bone formation and bone resorption, devoid of any side effect...
May 7, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29733427/chimeric-hdac-inhibitors-comprehensive-review-on-the-hdac-based-strategies-developed-to-combat-cancer
#15
REVIEW
Heba M Hesham, Deena S Lasheen, Khaled A M Abouzid
Recently, molecular hybridization paradigm became an interesting and smart way to defeat the multifaceted cancer disease by a single molecular entity that acts via several mechanisms just like a magic bullet. Also, HDAC is an important epigenetic target in drug discovery, and the HDAC inhibitors showed successful pattern as cytotoxic agents. Because of their flexible structure activity relationship, it was easy to link them to other anticancer scaffolds. So, many dual action HDAC inhibitors have been developed and most of these hybrids have higher potency than the constituting parents in fighting of the cancer cells...
May 7, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29727025/small-molecule-inhibitors-of-mammalian-thioredoxin-reductase-as-potential-anticancer-agents-an-update
#16
REVIEW
Junmin Zhang, Baoxin Zhang, Xinming Li, Xiao Han, Ruijuan Liu, Jianguo Fang
Mammalian thioredoxin reductase (TrxR) enzymes are homodimeric flavin proteins sharing a unique yet essential selenocysteine residue at their C-terminus. TrxRs, together with their endogenous substrate thioredoxins, play a crucial role in regulating diverse cellular redox events. A wealth of evidence from both clinic observations and bench studies supports that overactivation/dysfunction of TrxRs has a close link to the onset and development of various diseases, such as cancer and neurodegeneration. Thus, an increasing interest has been attracted to find small molecule modulators of TrxRs during the past years...
May 4, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29727017/recent-advances-in-the-discovery-and-development-of-factor-xi-xia-inhibitors
#17
REVIEW
Rami A Al-Horani, Daniel K Afosah
Factor XIa (FXIa) is a serine protease homodimer that belongs to the intrinsic coagulation pathway. FXIa primarily catalyzes factor IX activation to factor IXa, which subsequently activates factor X to factor Xa in the common coagulation pathway. Growing evidence suggests that FXIa plays an important role in thrombosis with a relatively limited contribution to hemostasis. Therefore, inhibitors targeting factor XI (FXI)/FXIa system have emerged as a paradigm-shifting strategy so as to develop a new generation of anticoagulants to effectively prevent and/or treat thromboembolic diseases without the life-threatening risk of internal bleeding...
May 4, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29719055/proteasome-mediated-proteostasis-novel-medicinal-and-pharmacological-strategies-for-diseases
#18
REVIEW
Ribhav Mishra, Arun Upadhyay, Vijay Kumar Prajapati, Amit Mishra
Proteins actively participate in a wide range of cellular physiological functions. But aggregation of proteins results in cytotoxicity, and unwanted aggregation of misfolded proteins often causes many diseases. During abnormal protein aggregation events, cells try to cope against such deleterious consequences because of the remarkable functional attempts of two distinct proteolytic mechanisms. These tightly regulative and signaling mechanisms are autophagy pathway and ubiquitin proteasome system. Proteasome complex system holds the elimination capacity of intracellular aberrant protein aggregation...
May 2, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29659056/in-honor-of-professor-li-he-zhang-on-the-occasion-of-his-80th-birthday
#19
EDITORIAL
Xinjing Tang, Shaoru Wang
No abstract text is available yet for this article.
May 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29512174/carbohydrate-based-vaccines-for-oncotherapy
#20
REVIEW
Meng-Man Wei, Yong-Shi Wang, Xin-Shan Ye
Cancer is still one of the most serious threats to human worldwide. Aberrant patterns of glycosylation on the surface of cancer cells, which are correlated with various cancer development stages, can differentiate the abnormal tissues from the healthy ones. Therefore, tumor-associated carbohydrate antigens (TACAs) represent the desired targets for cancer immunotherapy. However, these carbohydrate antigens may not able to evoke powerful immune response to combat with cancer for their poor immunogenicity and immunotolerance...
May 2018: Medicinal Research Reviews
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