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Current Drug Targets

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https://www.readbyqxmd.com/read/28078985/designing-isoform-selective-inhibitors-against-classical-hdacs-for-effective-anticancer-therapy-insight-and-perspectives-from-in-silico
#1
Shabir Ahmad Ganai
Histone deacetylase inhibitors, the small molecules modulating the biological activity of histone deacetylases are emerging as potent chemotherapeutic agents. Despite their considerable therapeutic benefits in disease models, the lack of isoform specificity culminates in debilitating off target effects, raising serious concerns regarding their applicability. This emphasizes the pressing and unmet medical need of designing isoform selective inhibitors for safe and effective anticancer therapy. Keeping these grim facts in view, the current article sheds light on structural basis of off-targeting...
12, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28068895/can-surgery-for-inflammatory-bowel-disease-be-personalized
#2
Antonino Spinelli, Alessandra Marano, Claudio Bacchelli, Nicolò Maria Mariani, Marco Montorsi, Paulo Gustavo Kotze
In the treatment of Inflammatory Bowel Diseases (IBD) despite advances in medical therapies, surgery has maintained a leading role in the management of complications of the disease, as well as in cases of failure of medical therapy. Surgery has become more and more minimally invasive, struggling for a difficult balance between guidelines and personalized treatment tailored on the single patient's need. In the present paper, the authors discuss the possible role for a personalization in debated fields of surgical treatment of Crohn&s disease and ulcerative colitis...
January 5, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28056748/pro-inflammation-cytokines-new-potential-therapeutic-targets-for-obesity-related-bone-disorders
#3
Tian Tian Wang, Chenglin Qi He, Xi Jie Yu
Obesity was traditionally thought as a positive regulator on the strength of bone. With the in-depth study, obesity is considered as a major risk factor for osteoporosis. Some pro-inflammation cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) are the factors that fat uses to negatively regulate bone metabolism. Obese people and animals show a higher level of serum TNF-α and IL-6, which are produced by macrophages derived from adipose tissue. These pro-inflammation cytokines regulate the proliferation and apoptosis of adipocyte, promote lipolysis, inhibit lipid synthesis and decrease blood lipids through autocrine and paracrine way...
January 4, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28034277/the-two-faces-of-interleukin-17a-in-atherosclerosis-interleukin-17a-and-atherosclerosis
#4
Mohammadreza Akhavanpoor, Hamidreza Akhavanpoor, Christian A Gleissner, Susanne Wangler, Andreas O Doesch, Hugo A Katus, Christian Erbel
A complex network of different cytokines and chemokines modulate atherosclerosis, a chronic inflammatory disease. Interleukin-17A (IL-17A) is expressed by different leukocyte subsets such as CD4+IL-17+ T cells (Th17), γδ T cells, natural killer cells, natural killer T cells, and neutrophils. IL-17A plays an important role in host defense and is involved in the pathology of different autoimmune and inflammatory diseases. Recent studies demonstrate an association of IL-17A with atherosclerosis. IL-17A seems to have primarily pro-inflammatory effects in atherogenesis, although there are partially controversial results in the literature...
December 29, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28031014/cebp-epigenetic-dysregulation-as-a-drug-target-for-the-treatment-of-hematologic-and-gynecologic-malignancies
#5
Chengming Sun, Ping Duan, Caifu Luan
The CCAAT/enhancer binding proteins (C/EBPs) form a family of transcription factors regulating many genes' expression in a variety of cells/tissues/organs at different developmental stages. With their capability of binding to a loosely defined consensus DNA sequence and through extensive protein-protein interactions, C/EBPs modulate diverse functions including cell differentiation, metabolism, and immune response, under both physiological and pathological conditions such as the establishment of hematological lineages, the maintenance of normal reproductive function, and the development of malignant disease...
December 28, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28025940/a-mini-review-on-the-chemistry-and-neuroprotective-effects-of-silymarin
#6
Kasi Pandima Devi, Dicson Sheeja Malar, Nady Braidy, Seyed Mohammad Nabavi, Seyed Fazel Nabavi
The plant milk thistle and silymarin has been traditionally used as a natural remedy for the treatment of various ailments including neurological disorders such Alzheimer's and Parkinson's Disease and cerebral ischemia for over 2000 years. The neuroprotective effects conferred by silymarin include modulation of various antioxidant mechanisms, and several kinases involved in cell signaling pathways, inhibition of the inflammatory response generated during neurodegeneration, neurotropic effects, regulation of neurotransmitters and inhibition of apoptosis...
December 27, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28025939/serotonin-selective-reuptake-inhibitors-ssris-and-female-sexual-dysfunction-fsd-hypothesis-on-its-association-and-options-of-treatment
#7
Nurul Azmi Mahamad Rappek, Hatta Sidi, Jaya Kumar, Sazlina Kamarazaman, Srijit Das, Ruziana Masiran, Najwa Baharudin, Muhammad Hatta
Sexual dysfunctions are commonly seen in women on selective serotonin reuptake inhibitors (SSRIs). The complexities of female sexual functioning are reflected through modulation of inter-playing factors like the neuropsychophysiological factors, inter-personal and relationship issue, psychiatric co-morbidities and physical disorder. The incidence of SSRIs-induced FSD is difficult to estimate because of the potentially confounding effects of SSRIs, presence of polypharmacy, marital effect, socio-cultural factors and due to the design and assessment problems in majority of the studies...
December 27, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28025941/bone-a-fertile-soil-for-cancer-metastasis
#8
Thomas Coughlin, Ricardo Romero Moreno, Devon Mason, Lukas Nystrom, Joel Boerckel, Glen Niebur, Laurie E Littlepage
Bone is one of the most common and most dangerous sites for metastatic growth across cancer types, and bone metastasis remains incurable. However, the processes by which cancers preferentially metastasize to bone are not well understood. In this review we summarize the morphological features, physical properties, and cell signaling events that make bone a unique site for metastasis and bone remodeling. The signaling crosstalk between the tumor cells and bone cells begins a vicious cycle, which describes the self-sustaining feedback loop between the tumor cells and the bone microenvironment composed of osteoclasts, osteoblasts, other bone marrow cells, bone matrix, and vasculature to support both tumor growth and bone destruction...
December 26, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28017129/kynurenine-system-and-multiple-sclerosis-pathomechanism-and-drug-targets-with-an-emphasis-on-laquinimod
#9
Zsófia Majláth, Ádám Annus, László Vécsei
Multiple sclerosis is a common chronic, disabling autoimmune neurological disease affecting mainly young adults. In its pathomechanism, neurodegenerative and acute inflammatory characteristics are both involved. Disease-modifying therapies aim to reduce relapse-rate and slow down the deterioration in neurological functions. The currently available therapies fail to exert neuroprotective effects and most of them are associated with potentially toxic side-effects, therefore, ongoing research aims to develop novel drug candidates to cover these therapeutic gaps...
December 23, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28017126/recent-advances-in-transcranial-focused-ultrasound-fus-triggered-brain-delivery
#10
Nidhi Nainwal
Successful delivery of therapeutic agents in the brain is very challenging, which makes treatment of various brain disorders very difficult. One of the major causes of this difficulty is the presence of physiological barriers in the brain like blood brain barrier (BBB) and blood cerebro-spinal fluid (CSF) barrier. These barriers are very specific and restrict the entry of water soluble agents and ionized molecule. Only lipid soluble and small molecular size agents are allowed to enter into the brain. But there are several serious brain diseases in which the use of only conventional small molecular mass lipophilic drug is not effective...
December 22, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28017125/review-of-theoretical-models-to-study-natural-products-with-antiprotozoal-activity
#11
Miguel A Herrera-Rueda, Gabriel Navarrete-Vázquez, Francisco Aguirre-Crespo, María Guadalupe Maldonado-Velazquez, Jorge Vergara-Galicia, Hilario Chi Canul, Xerardo García-Mera, Francisco J Prado-Prado
There exists many pathogen parasite species with different susceptibility profiles of antiparasitic drugs. Unfortunately, almost QSAR models predict the biological activity of drugs against only one parasite species. Consequently, predicting the probability with which a drug is active against different species with a single unified model is a goal of major importance. In doing so, we use Markov Chains theory to calculate new multi-target spectral moments to fit a QSAR model that for the first time, can predicta meet-QSAR model for more than 40,000 cases obtained from databases CHEMBL against more than 35 proteins of 4 parasite species obtained from the Protein Data Bases (PDB)...
December 22, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28003005/targeting-cysteine-proteases-from-plasmodium-falciparum-a-general-overview-rational-drug-design-and-computational-approaches-for-drug-discovery
#12
Boris D Bekono, Fidele Ntie-Kang, Luc C Owono Owono, Eugene Megnassan
The Plasmodium falciparum cysteine proteases, also known as falcipains, are involved in different erythrocytic cycle processes of the malaria parasite, e.g. hydrolysis of host haemoglobin, erythrocyte invasion, and erythrocyte rupture. With the biochemical characterization of four falcipains so far, FP-2 (falcipain-2) and FP-3 (falcipain-3), members of the papain-like CAC1 family, are essential haemoglobinases. They could therefore be referred to as potential anti-malarial drug targets in the search for novel therapies, which could ease the burden caused by the increasing resistance to current anti-malarial drugs...
December 21, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28000547/pharmacology-and-toxicology-of-polyphenols-with-potential-as-neurotropic-agents-in-non-communicable-diseases
#13
Agustín Ramiro Miranda, Claudia Albrecht, Mariela Valentina Cortez, Elio Andrés Soria
BACKGROUND: The central nervous system (CNS) is involved in organic integration. Nervous modulation via bioactive compounds can modify metabolism in order to prevent systemic non-communicable diseases (NCDs). Concerning this, plant polyphenols are proposed as neurotropic chemopreventive/therapeutic agents, given their redox and regulating properties. OBJECTIVE: To review polyphenolic pharmacology and potential neurological impact on NCDs. METHOD: First, polyphenolic chemistry was presented, as well as pharmacology, i...
December 20, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27993111/targeting-legumain-as-a-novel-therapeutic-strategy-in-cancers
#14
Chun Wai Mai, Felicia Fei-Lei Chung, Chee Onn Leong
Recent reports indicate that the tumor microenvironment plays a pivotal role in cancer development and progression, leading to a paradigm shift in the way cancer is studied and targeted. In contrast to traditional approaches, where only tumor cells are targeted for treatment, an emerging approach is to develop therapeutics which target the tumor microenvironment while complementing or enhancing current treatments. Legumain (LGMN) is a newly identified target which is highly expressed in the tumor microenvironment and in tumor cells, and holds potential both as a biomarker and as a therapeutic target...
December 16, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27993112/understanding-the-pathophysiology-of-premature-ejaculation-bridging-the-link-between-pharmacological-and-psychological-interventions
#15
Hatta Sidi, Farid Yusof, Srijit Das, Marhani Midin, Jaya Kumar, Muhammd Hizri Hatta
Premature ejaculation (PE) is one of the commonest male sexual dysfunctions. It is characterized by ejaculation which occurs before or soon after vaginal penetration, which causes significant psychological distress to the individual, and his partner. The exact cause of PE is still unknown but several mechanisms are proposed, and these involve complex interactions of neurophysiological, psychosocial, and cognitive factors. We discuss the role of serotonin, nitric oxide, phosphodiesterase enzymes and other neurotransmitters...
December 15, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27924725/anticancer-drug-targets-of-salvia-phytometabolites-chemistry-biology-and-omics
#16
Da-Cheng Hao, Guang-Bo Ge, Pei-Gen Xiao
Salvia displays diverse anticancer properties, which are attributable to their diterpene and phenolic contents. There is no comprehensive review on the anticancer diversity and molecular targets of Salvia components. We investigate the diversity and molecular targets of Salvia phytometabolites responsible for the prevention and treatment of cancer and sarcoma. Traditional therapeutic knowledge suggests that Salvia species can be used to develop anticancer drugs. Lots of concerns have been raised for tanshinone (Tan) IIA and cryptotanshinone...
December 7, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27919208/is-metformin-a-therapeutic-paradigm-for-colorectal-cancer-insight-into-the-molecular-pathway
#17
Zar Chii Thent, Nurul Hannim Zaidun, Fairuz Azmi, Mu Izuddin Senin, Haszianaliza Haslan, Ahmad Ruzain Salehuddin
Colorectal cancer (CRC) remains one of the major leading causes of cancer related morbidity and mortality. Apart from the conventional anti-neoplastic agents, metformin, a biguanide anti-diabetic agent, has recently found to have anti-cancer property. Several studies observed the effect of metformin towards its anti-cancer effect on colon or colorectal cancer in diabetic patients. However, only a few studies showed its effect on colorectal cancer in relation to the non-diabetic status. The present review aimed to highlight the insight into the molecular pathway of metformin towards colorectal cancer in the absence of diabetes mellitus...
December 5, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27894236/virulence-factor-targeting-of-the-bacterial-pathogen-staphylococcus-aureus-for-vaccine-and-therapeutics
#18
Trevor Kane, Katelyn Carothers, Shaun Lee
Staphylococcus aureus is a major bacterial pathogen capable of causing a range of infections in humans from gastrointestinal disease, skin and soft tissue infections, to severe outcomes such as sepsis. Staphylococcal infections in humans can be frequent and recurring, with treatments becoming less effective due to the growing persistence of antibiotic resistant S. aureus strains. Significant research into virulence factors produced by S. aureus have yielded many important findings regarding specific mechanisms that contribute to its overall pathogenesis...
November 28, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27894237/new-insight-in-improving-therapeutic-efficacy-of-antipsychotic-agents-an-overview-of-improved-in-vitro-and-in-vivo-performance-efficacy-upgradation-and-future-prospects
#19
Zahid Hussain, Hnin Ei Thu, Ahmad Nazrun Shuid
Psychotic disorders are severe mental disorders that rigorously affect patient personality, critical thinking, and perceptional ability. High prevalence, global dissemination and limitations of conventional pharmacological approaches compel a significant burden to the patient, medical professionals and the healthcare system. To date, numerous orally administered therapies are available for the management of depressive disorders, schizophrenia, anxiety, bipolar disorders and autism spectrum problems. However, poor water solubility, erratic oral absorption, extensive first-pass metabolism, low oral bioavailability and short half-lives are major factors which limit the pharmaceutical significance and therapeutic feasibility of these agents...
November 25, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27890000/reproductive-toxicity-of-t-cells-in-early-life-abnormal-immune-development-and-postnatal-diseases
#20
Han-Xiao Liu, Aifang Jiang, Ting Chen, Wen Qu, Hui-Yi Yan, Jie Ping
Immunity is a balanced status with adequate biological defenses to recognize and fight "non-self", as well as adequate tolerance to recognize "self". To maintain this immune homeostasis, a well-organized T cell immune network is required, which in part depends on the well-controlled development of alternative effector T cells, with different cytokine repertoires. Recent research has pointed that developing fetal T cells network is a remarkably sensitive toxicological target for adverse factors in early life...
November 24, 2016: Current Drug Targets
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