Abstract:
:Despite the significant progresses made in antiretroviral therapy, current drugs still cannot cure or prevent HIV infection. And all drugs continue to select for drug-resistant HIV strains. Consequently, new antiretroviral drugs are constantly being developed. To ensure safety, these drugs are usually designed to inhibit viral proteins. But cellular proteins are also emerging as potential targets for new antiretroviral drugs. Two drugs that target cellular proteins inhibit HIV replication in vitro, hydroxyurea (HU) and pharmacological cyclin-dependent kinase inhibitors (PCIs). HU has been tested in clinical trials, commonly in combination therapies. PCIs, which are newer drugs, have just started to be tested in animal models of HIV-induced disease. Herein, we will review the HIV replication cycle and discuss the biological causes why strains resistant to antiviral drugs are so easily selected for. We will then discuss current antiretroviral drugs and HU before focusing on PCIs. PCIs have demonstrated to be effective against wild-type and drug-resistant strains of HIV in vitro, while selecting for no drug resistance. PCIs are additive with conventional antiviral drugs against herpes simplex virus, which suggests that they could also be additive with antiretroviral drugs. Since PCIs are proving surprisingly safe in human clinical trials (against cancer), they may be developed as clinical antiretroviral drugs in the near future. Recent and exciting studies indicate that PCIs ameliorate the pathogenesis of an animal model of HIV-induced nephropathy. We can expect that the full potential of PCIs as antiretroviral drugs will be explored in the coming years.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Provencher VM,Coccaro E,Lacasse JJ,Schang LMdoi
10.2174/1381612043382422subject
Has Abstractpub_date
2004-01-01 00:00:00pages
4081-101issue
32eissn
1381-6128issn
1873-4286journal_volume
10pub_type
杂志文章,评审abstract::Reduction strategies of blood pressure, as a modifiable cardiovascular risk, are currently based on office assessment of brachial artery blood pressure. However, antihypertensive treatment based on brachial BP values reduces cardiovascular risk but cannot completely reverse the hypertension-induced risk of morbidity e...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666141023164530
更新日期:2015-01-01 00:00:00
abstract::CHD is one of the most common serious chronic conditions in postmenopausal women and leads to extremely high risk for recurrent myocardial infarction and death. On the basis of the currently available randomized clinical-trial results the role of conventional HRT for treatment and prevention of CHD is rapidly evolving...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161205774913237
更新日期:2005-01-01 00:00:00
abstract::Guanine-rich sequences found in telomeres and oncogene promoters have the ability to form G-quadruplex structures. In this paper we describe the use of a virtual screening assay to search a database of FDA-approved compounds for compounds with the potential to bind G-quadruplex DNA. More than 750 telomerase inhibitors...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612811319120004
更新日期:2013-01-01 00:00:00
abstract::Periodontal disease is chronic inflammation of periodontal tissues resulting in formation of periodontal pockets, periodontal attachment loss and progressive destruction of the ligament and alveolar bone. This review gives an update on periodontal disease pathogenesis, which is important for the development of novel m...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150531171829
更新日期:2015-01-01 00:00:00
abstract::Stimulant use disorders are an unrelenting public health concern worldwide. Agonist replacement therapy is among the most effective strategies for managing substance use disorders including nicotine and opioid dependence. The present paper reviewed clinical data from human laboratory self-administration studies and cl...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161281940131209142843
更新日期:2013-01-01 00:00:00
abstract::Neuroinflammation is a common characteristic of several mental health conditions such as major depression, bipolar disorder, post-traumatic stress disorder (PTSD) and schizophrenia (SCHZ). Inflammatory processes trigger and/or further deteriorate mental functions and are regarded as targets for therapeutic drug develo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161282210160304112511
更新日期:2016-01-01 00:00:00
abstract::Regulatory T lymphocytes (Tregs) are specialized for immune suppression and are important regulators of the immune response in various settings. Tregs actively suppress enteroantigen-reactive cells and contribute to the maintenance of intestinal immune homeostasis. Distinct Treg subsets coexist in the intestinal mucos...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787846784
更新日期:2009-01-01 00:00:00
abstract::Fusion proteins have been well-studied and widely applied in biopharmaceutics. Albumin fusion proteins are simple to construct, easy to purify, and stable to formulate. One main application of fusion protein is to extend the plasma half-life of therapeutic proteins and peptides. Albiglutide for diabetes treatment is t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150302120047
更新日期:2015-01-01 00:00:00
abstract::Diet has a high relevance in health. Hypertension is a major risk factor for cardiovascular diseases and has an important impact on public health, and consequently on countries economy. Scientific research gathered strong evidence about the role of several dietary factors either in etiology or in treatment/prevention ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802651670
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Inhibition of hepatic fibrosis is an attainable objective in managing the chronic liver disease. The present study aimed to investigate possible defensive effects of metformin on the activities of antioxidant enzymes, hydroxyproline content, and biochemical factors in bile duct ligation (BDL)-induced cholest...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612824666181003114108
更新日期:2018-01-01 00:00:00
abstract::The disappointing results in long-term survival of patients affected by non-small cell lung cancer (NSCLC) may be attributed, at least in part, to the lack of knowledge on the way by which genetic characteristics in normal and neoplastic cells affect responsiveness as well as metabolism of chemotherapy and new targete...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113196660756
更新日期:2014-01-01 00:00:00
abstract::Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with premature mortality, severe morbidity, and functional impairment leading to considerable financial burden for both patients and society. Since disease progression and complications can differ from one patient to another, genetic markers are of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140825123407
更新日期:2015-01-01 00:00:00
abstract::Crohn's disease and ulcerative colitis are the two principal forms of inflammatory bowel disease (IBD). The root causes of these chronic and acute immunological disorders are unclear, but intestinal microorganisms are known to play a key role in the initiation and maintenance of disease. However, at present, there is ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788168146
更新日期:2009-01-01 00:00:00
abstract::Early life stress is considered a risk factor for the development of many diseases in both adolescence and adulthood. It has been reported that chronic stress (for instance, due to maternal separation during breast feeding), causes damage to the central nervous system at the level of neurons and glial cells, which are...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170224111641
更新日期:2018-02-12 00:00:00
abstract:AIM:The effect of endovascular aneurysm repair in patients treated for abdominal aortic aneurysm has not been clearly defined. The objective of the present article was to provide a contemporary literature review and perform an analysis to determine the effect of EVAR on renal function in the early post-operative period...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666191129094923
更新日期:2019-01-01 00:00:00
abstract::Pulmonary surfactant, a complex of lipids and proteins, functions to keep alveoli from collapsing at expiration. Surfactant proteins A (SP-A) and D (SP-D) belong to the collectin family and play pivotal roles in the innate immunity of the lung. Pulmonary collectins directly bind with broad specificities to a variety o...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206775474387
更新日期:2006-01-01 00:00:00
abstract::P2Y12 adenosine di-phosphate (ADP) receptor antagonists are critical to reduce thrombotic recurrences in acute coronary syndromes patients and for those undergoing percutaneous coronary revascularization. Multiple lines of evidence suggest that the level of on-treatment platelet reactivity inhibition with P2Y12 ADP re...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803251934
更新日期:2012-01-01 00:00:00
abstract::Parkinson's disease (PD) is a movement disorder caused by degeneration of the nigrostriatal dopamine (DA) neurons in the substantia nigra pars compacta and the resultant deficiency in the neurotransmitter DA at the nerve terminals in the striatum. We and other investigators found increased levels of pro-inflammatory c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053381620
更新日期:2005-01-01 00:00:00
abstract::Guidelines for the treatment of hypertension allow a wide range of choices to the physicians; however some differences are present about the preferred drugs to start treatment. The most important aim remains an adequate decrease of blood pressure, something not perfectly obtained in the general population, but some cl...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799436575
更新日期:2012-01-01 00:00:00
abstract::Phase-change contrast agents (PCCAs) for ultrasound-based applications have resulted in novel ways of approaching diagnostic and therapeutic techniques beyond what is possible with microbubble contrast agents and liquid emulsions. When subjected to sufficient pressures delivered by an ultrasound transducer, stabilized...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212800099883
更新日期:2012-01-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) includes liver diseases ranging from simple steatosis to progressive forms characterized by high rates of complications and mortality, namely fibrosis, cirrhosis and hepatocellular carcinoma. Identification of patients with simple steatosis who will evolve to a more severe liv...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191122101021
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Protective effect of pretreatment with ghrelin against different forms of acute pancreatitis (AP) has been recently reported. Moreover, the healing properties of this peptide have been proved in AP evoked by cerulein. However, no studies have investigated whether the administration of ghrelin affects the cou...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612821666150105152553
更新日期:2015-01-01 00:00:00
abstract::The serotonergic system is involved in pathomechanisms of both epilepsy and neuropathic pain. So far, participation in the epileptogenesis and maintenance of epilepsy was proved for 5-HT1A, 5-HT2C, 5-HT3, 5-HT4 and 5-HT7 receptors as well as 5-HTT serotonin transporter. Depending on the receptor type or its localizati...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666141121114917
更新日期:2015-01-01 00:00:00
abstract::Protein palmitoylation is a fundamental and reversible post-translational lipid modification that involves a series of biological processes. Although a large number of experimental studies have explored the molecular mechanism behind the palmitoylation process, the computational methods has attracted much attention fo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201112142826
更新日期:2020-11-12 00:00:00
abstract::In recent years, combination of different types of therapies using nanoparticles has emerged as an advanced strategy for cancer treatment. Most of all, combination of chemotherapeutic drug and siRNA in nanoformulation has shown a great potential, because siRNA-mediated specific gene silencing can compensate for the in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150531165059
更新日期:2015-01-01 00:00:00
abstract::Ischaemic stroke of the brain accounts for about one third of all deaths in industrialized countries. Many of the patients who survive are severily impaired. Thus, there is an enormous need for pharmacotherapy for the treatment of ischaemic stroke. Why is such a treatment not available yet? Are the pathophysiological ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612024607135
更新日期:2002-01-01 00:00:00
abstract::Over the past decade, Lymphocyte Function-Associated Antigen-1 (LFA-1, alphaLbeta2, CD11a/CD18) has emerged as an attractive therapeutic target for the treatment of multiple inflammatory diseases. Its established role in the trafficking and activation of leukocytes coupled with the recent elucidation of the global con...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777947731
更新日期:2006-01-01 00:00:00
abstract::Abnormal regulation of the ubiquitin-proteasome system (UPS) has been known to be involved in the pathogenesis of a variety of human diseases. A number of studies have focused on the identification of small modifiers for the UPS. Even though the proteasome inhibitor Bortezomib (Velcade®) has been approved for the ther...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319220013
更新日期:2013-01-01 00:00:00
abstract::The last decades have witnessed an explosion in studies of the role of amyloid-β (Aβ) in the progress of the neurodegenerative disorder Alzheimer's disease (AD) and it is now widely accepted that Aβ is related to the pathogenesis of AD. For example, studies have shown that Aβ is neurotoxic and that the neurotoxicity o...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797416039
更新日期:2011-01-01 00:00:00
abstract:Background:Capsinoids (CSN), the novel non-pungent capsaicin analogs have been reported to promote metabolic health and exercise tolerance. However, the effect of CSN on fat oxidation and changes in skeletal muscle glycogen levels during post-exercise recovery has not been investigated in humans. Purpose:We examined t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200824104856
更新日期:2020-08-23 00:00:00