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Current Drug Targets

Carlos G Ferreira, Andrea Nicolini, Liliana Dalurzo, Stephen Stefani, Vanessa Teiche, Natasha Leighl
The development of therapies that restore or activate the host immune response - the so called "immuno-oncologic" therapy - has improved the survival of some cancer patients harboring specific tumor types. These drugs, however, are very expensive which has greatly limited their use and consequently reduced the number of patients who could likely benefit. Not to mention, that the proportion of patients who display a clinical benefit from therapy is limited. Thus, from a clinical e health economics perspective there is a pressing need to identify and treat those patients for whom a given immuno-oncologic therapy is most likely to be beneficial...
September 10, 2018: Current Drug Targets
Rakesh Sharma
Stem Cell Research and Tissue Engineering, in present time, have emerged as a legalized and regulated stem cell treatment option globally, but scientifically, their success is unestablished. Novel stem cell-based therapies have evolved as innovative and routine clinical solutions by commercial companies and hospitals across the world. Such rampant spread of stem cell clinics throughout UK, US, Europe and Asia reflect the public encouragement of benefits to incurable diseases. However, ever growing stem cell therapy developments need constant dogwatch and careful policy making by government regulatory bodies for prompt action in case of any untoward public concern...
August 30, 2018: Current Drug Targets
Shiqi Luo, George Binh Lenon, Harsharn Gill, Heidi Yuen, Angela Wei Hong Yang, Andrew Hung, Linh Toan Nguyen
BACKGROUND: Overweight or obesity has become a world-wide health concern. Pharmacotherapies are introduced because lifestyle modifications alone are insufficient for weight management. The treatment outcomes of current approved anti-obesity agents are not satisfying due to drug-related intolerances. Therefore natural therapies including herbal medicines are popular alternatives for weight reduction; however there are limited studies about their mechanism of actions Methods: Five databases include PubMed, Scopus, Google Scholar, Science direct, Proquest were searched in order to investigate the targets and safety profiles of the current and past anti-obesity drugs that have been approved by Food and drug administration (FDA) or European Medicines Agency (EMA)...
August 30, 2018: Current Drug Targets
Yanzhou Yang, Hoi-Hung Cheung, Cheng Zhang, Ji Wu, Wai-Yee Chan
In previous studies, oxidative stress damage was solely considered to be the mechanism of ovarian aging, and several antioxidants were used to delay ovarian aging. But recently, more reports have found that endoplasmic reticulum stress, autophagy, sirtuins, mitochondrial dysfunction, telomeres, gene mutation, premature ovarian failure, and polycystic ovary syndrome are all closely related to ovarian aging, and these factors all interact with oxidative stress. These novel insights on ovarian aging are summarized in this review...
August 28, 2018: Current Drug Targets
Qinyuan Li, Qian Yi, Lin Tang, Siying Luo, Yuan Tang, Guangli Zhang, Zhengxiu Luo
BACKGROUND: Air pollution is a major cause of asthma exacerbation. Most studies have proven that exposure to coarse and fine particulate matter is associated with asthma exacerbation. Ultrafine particles (UFP, aerodynamic diameter ≤ 0.1 μm) are the smallest airborne particles, which are capable of penetrating deep into the lungs because of their small size. Toxicological studies have suggested that exposure to UFPs may have serious effects on respiratory health. However, epidemiological evidence on the effects of UFP exposure on asthma exacerbation remains unclear...
August 28, 2018: Current Drug Targets
Amanda Almeida de Oliveira, R Clinton Webb, Kenia Pedrosa Nunes
Diabetes is one of the most concerning diseases in modern times. Despite considerable advances in therapeutic management, the prevalence of diabetes and its contribution to death and disability continue to be a major health problem. Diabetic vasculopathies are the leading cause of mortality and morbidity in diabetic patients. Its pathophysiology includes oxidative stress, advanced glycation end products, and a low-grade inflammatory state. Lately, actions of the innate immune system via Toll-like receptors (TLRs) have been suggested as a new insight in this field...
August 20, 2018: Current Drug Targets
Jahangir Alam, Lalit Sharma
Alzheimer's, a degenerative cause of the brain cells, is called as a progressive neurodegenerative disease and appears to have a heterogeneous etiology with main emphasis on amyloid-cascade and hyperphosphorylated tau-cascade hypotheses, that are directly linked with macromolecules called enzymes such as β- & γ-secretases, colinesterases, transglutaminases, and glycogen synthase kinase (GSK-3), cyclin-dependent kinase (cdk-5), microtubule affinity-regulating kinase (MARK). The catalytic activity of the above enzymes is the result of cognitive deficits, memory impairment and synaptic dysfunction and loss, and ultimately neuronal death...
August 19, 2018: Current Drug Targets
Armando Rojas, Miguel Morales, Ileana Gonzalez, Paulina Araya
The receptor for advanced glycation end products (RAGE) is an important cell surface receptor, which belongs to the IgG superfamily and now considered as a pattern recognition receptor. Because its relevance in many human clinical settings, it is now pursued as a very attractive therapeutic target. However, particular features of this receptor such as a wide repertoire of ligands with different binding domains, the existence of many RAGE variants as well as the presence of cytoplasmatic adaptors leading a diverse signaling, have represented important handicaps in the searching of successful pharmacological approaches to inhibit RAGE signaling...
August 19, 2018: Current Drug Targets
Anurag Singh Chauhan, Ganesh Chandra Sahoo, Manas Ranjan Dikhit, Pradeep Das
The H+-gated (proton) currents are widely present in brain sensory neuronal system and various studies identified the structural units and deciphered the physiological and pathological function of ion channels. The normal neuron requires an optimal pH to carry out its functions. In acidosis the ASICs (Acid-sensing Ion Channels) are activated in both the CNS (central nervous system) and PNS (peripheral nervous system). ASICs are related to degenerin channels (DEGs), epithelial sodium cation channels (ENaCs), and FMRF-amide (Phe-Met-Arg-Phe-NH2)-gated channels (FaNaC)...
August 19, 2018: Current Drug Targets
Rakesh Kumar Singh, Abul Kalam Najmi
OBJECTIVE: The primary focus of this review is to highlight the current and emerging pro-inflammatory role of MK2 kinase signaling in p38MAPK pathway and to provide a detailed evaluation on the prospects of MK2 inhibition with special emphasis on the etiology of chronic inflammatory airway diseases, such as asthma, idiopathic pulmonary fibrosis, lung cancer, acute lung injury and acute respiratory distress syndrome. BACKGROUND: Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is a serine-threonine kinase downstream to p38MAPK and is activated directly by stress and inflammatory signal through p38 phosphorylation...
August 16, 2018: Current Drug Targets
Gustavo H Oliveira-Paula, Jose E Tanus-Santos
Hypertension is usually associated with deficient nitric oxide (NO) bioavailability, and therefore stimulating NO activity is an important antihypertensive strategy. Recently, many studies have shown that both nitrite and nitrate anions are not simple products of NO metabolism and indeed may be reduced back to NO. While enzymes with nitrite-reductase activity capable of generating NO from nitrite may contribute to antihypertensive effects of nitrite, another mechanism involving the generation of NO-related species in the stomach from nitrite has been validated...
August 16, 2018: Current Drug Targets
Dorina Lauritano
BACKGROUND: This review aims to address procedures and indications for the application of the adipose-derived stem cells (ADSCs) for regenerative dentistry. ADSCs have rarely been used in this particular field; conversely, experience from other clinical fields and basic research seems to recommend the suitability of this application. AIMS AND METHODS: We reviewed 32 out of 193 articles on Medline sorted by the relevance option. The main purpose of this paper is to perform a short review of the application of stem cells in regenerative dentistry, describing a multilineage differentiation as a safe and useful alternative way of harvesting and selection of ADSCs...
August 16, 2018: Current Drug Targets
Duraiswamy Basavan, Nehru Sai Suresh Chalichem, Suresh K Mohan Kumar
As the global aged population is increasing tremendously, time has come to concentrate on tail end life stage diseases. Alzheimer's disease (AD) is one such disease whose origin is an enigmatic, impacts later stage of life drastically due to irreparable damage of cognition. The characteristic feature of the disease is the accumulation of neurotoxic amyloid-beta (Aβ) and hyper phosphorylated Tau protein as fibrillary tangles. Several research reports obtained from in vitro and in vivo studies proved the efficacy of herbals in culminating neurodegenerative changes of AD by acting through various molecular pathways at various stages...
August 12, 2018: Current Drug Targets
Yan Hu, Yi Lu, Shuo Wang, Mengying Zhang, Xiaosheng Qu, Bing Niu
BACKGROUND: Globally the number of cancer patients and deaths are continuing to increase yearly, and cancer has, therefore, become one of the world's highest causes of morbidity and mortality. In recent years, the study of anticancer drugs has become one of the most popular medical topics. OBJECTIVE: In this review, in order to study the application of machine learning in predicting anticancer drugs activity, some machine learning approaches such as Linear Discriminant Analysis (LDA), Principal components analysis (PCA), Support Vector Machine (SVM), Random forest (RF), k-Nearest Neighbor (kNN), and Naïve Bayes (NB) were selected, and the examples of their applications in anticancer drugs design are listed...
August 9, 2018: Current Drug Targets
Agnieszka Jankowska, Artur Swierczek, Elzbieta Wyska, Alicja Gawalska, Adam Bucki, Maciej Pawlowski, Grazyna Chlon-Rzepa
Phosphodiesterase 10A (PDE10A) is a double substrate enzyme that hydrolyzes second messenger molecules such as cyclic-3',5'-adenosine monophosphate (cAMP) and cyclic-3',5'-guanosine monophosphate (cGMP). Through this process, PDE10A controls intracellular signaling pathways in the mammalian brain and peripheral tissues. Pharmacological, biochemical, and anatomical data suggest that disorders in the second messenger system mediated by PDE10A may contribute to impairments in central nervous system (CNS) function, including cognitive deficits as well as disturbances of behavior, emotion processing, and movement...
August 7, 2018: Current Drug Targets
Lavi Rani, Naveen Kumar Gautam
Diabetic nephropathy is the pathological alterations in kidney and is one of the major causes of kidney failure accounting for ~44% of all cases. In spite of the large mortality rate of diabetic nephropathy, accurate cures are not available for the disease at present. Identification of genetic determinants and understanding their role in the progression of disease will be an imperative step for developing diagnostic tool and therapy for the disease. Drosophila melanogaster is a genetically tractable model organism and is being used for understanding the genetic basis of several human diseases...
August 7, 2018: Current Drug Targets
Marisa Cabeza, Lucero Bautista, Marisol Guadalupe Bravo, Yvonne Heuze
Considerable progress has been made in learning about the physiology and biochemistry of the sebaceous glands and several of the diseases that affect this component of the skin. Of these diseases, acne has particular importance. Although it is associated with adolescence, because of the hormonal changes that take place in this stage, when it is severe it can cause depression. Moreover, in a considerable proportion of acne sufferers both adolescent and adult, it can produce tumors and deformation of the sebaceous glands...
August 7, 2018: Current Drug Targets
Marcin Wlodarczyk, Jakub Wlodarczyk, Pawel Siwinski, Jakub Fichna, Aleksandra Sobolewska-Wlodarczyk
Colorectal cancer (CRC) is a heterogeneous disease entity in terms of both molecular carcinogenesis and morphologic carcinogenesis multistep pathways. A better understanding of pathophysiology of tumors is necessary to develop modern and successful means of treatment in metastatic CRC. Over the last 5 years there has been a surge in interest in the molecular classification of colorectal cancer, as its clinical importance both for predicting prognosis and in guiding personalized treatment had been acknowledged...
August 3, 2018: Current Drug Targets
Gangliang Huang, Hao Cheng
Epothilone is a newly developed anti-tumor drug whose anti-tumor principle is to stop the cell cycle by binding to tubulin in tumor cells, promoting the polymerization of tubulin and inhibiting the depolymerization of microtubules. There are many analogs of epothilone and its derivatives: ixabepilone, epothilone B, sagopirone, epothilone D, 21-aminoepothilone B, and KOS-1584. This article will review the synthesis of epothilone B. The total synthesis includes double decomposition methods, macroscopic internalization methods and some other total synthesis methods and some other semi-synthetic methods, and reviews the advantages of its synthetic scheme...
August 3, 2018: Current Drug Targets
Natalia Tolloczko-Iwaniuk, Dorota Dziemianczyk-Pakiela, Beata Klaudia Nowaszewska, Katarzyna Celinska-Janowicz, Wojciech Miltyk
BACKGROUND AND OBJECTIVES: It is generally accepted that inflammatory cells found in the tumor microenvironment are involved in the neoplastic process, promoting cell proliferation, survival, and migration. Therefore, administering anti-inflammatory medication in cancer therapy seems to be justified. A potential pathway associated with the aforementioned issue is cyclooxygenase-2 inhibition, particularly as the overexpression of this enzyme has been proven to occur in cancer tissues and is also associated with a poor prognosis in several types of human malignancies...
August 3, 2018: Current Drug Targets
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