Abstract:
:Reverse transcriptase (RT) is one of the most important targets for HIV drug discovery. However, the emergence of resistant mutants has become one of the biggest challenges in HIV-1 RT drug discovery/development and attracted great research interests worldwide. It is particularly important to develop novel anti-HIV-1 RT agents that have improved potency and efficacy against the wild-type (WT) RT, but also target resistant RT forms. Previous crystal complex structures of HIV-1 RT revealed the interaction mechanism between the enzyme and inhibitors, which promoted the exploitation of inhibitor that had sufficient conformational flexibility to combat resistance. Hence, the potential flexibility of a drug should be part of the strategy considered in the early stages of designing drugs that are intended to be broadly effective against mutated targets associated with drug resistance. This review provides an overview of the state of the art in this field, including design strategies and challenges for medicinal chemists.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Hao GF,Yang SG,Yang GFdoi
10.2174/138161282005140214163439subject
Has Abstractpub_date
2014-01-01 00:00:00pages
725-39issue
5eissn
1381-6128issn
1873-4286pii
CPD-EPUB-20130513-4journal_volume
20pub_type
杂志文章,评审abstract::Providing novel treatments to help cancer patients live longer and have better lives remains one of the biggest challenges of the pharmaceutical industry. Today much is known about the molecular and genetic causes of cancers thus facilitating the development of novel targeted cancer drugs with improved risk-benefit ra...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784246234
更新日期:2008-01-01 00:00:00
abstract::Carboxylic acids are an important natural component as a final product or intermediates for syntheses. They are produced in plants, animals and also as products from biotechnological processes. This review presents the use of single hydroxide particles and layered double hydroxides as alternative adsorbents to remove ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666191226103623
更新日期:2020-01-01 00:00:00
abstract::Growth and metastasis of lung cancer requires a sequence of events, which alter the ability of neoplastic cells to adhere to themselves, to normal surrounding cells, or to the extracellular matrix. Interactions between cells are primarily mediated by four types of structures in the plasma membrane: gap junctions, tigh...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208785740162
更新日期:2008-01-01 00:00:00
abstract::The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cAMP-regulated Cl- channel whose major function is to facilitate epithelial fluid secretion. Loss-of-function mutations in CFTR cause the genetic disease cystic fibrosis. CFTR is required for transepithelial fluid transport in certain secretor...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990321
更新日期:2013-01-01 00:00:00
abstract::The activation of Corticotrophin Releasing-Factor (CRF) receptors in the brain is well established to coordinate the endocrine, behavioral, autonomic and visceral responses to stress. In addition, CRF receptors are also expressed within the gut where they exert biological actions and play a role in modulating stress-r...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170228142428
更新日期:2017-01-01 00:00:00
abstract::Cell therapy has been proposed to treat patients with end-stage heart failure. However, it has been suggested that the significant mechanical forces in an often ischaemic, inflamed, biochemically hostile environment may cause poor cell survival and retention. It is hypothesised that tissue engineering techniques could...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990442
更新日期:2014-01-01 00:00:00
abstract::It is generally accepted that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are related to insulin resistance and type 2 diabetes. Mitochondria use substrates from lipid and glucose metabolism in order to generate ATP, and when mitochondrial O2 consumption is decreased due to an altered metabolism th...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160209152033
更新日期:2016-01-01 00:00:00
abstract::Cancer and tumor have been major reasons for numerous deaths in this century across the world. Many strategies have been designed to treat, diagnose, or prevent cancer. The success of chemotherapy largely depends on drug targeting. The advent of nanotechnology has vastly improved drug delivery for targeting and diagno...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200720235752
更新日期:2020-01-01 00:00:00
abstract::The mechanisms and factors causing or influencing degenerative diseases require tailor-made solutions. Natural polysaccharides are among the most versatile building units of the novel drug delivery systems. Their properties can be easily tailored to specific needs because they depend not only on the first-order struct...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212800492831
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Attempts to reduce the burden may be proactive using biochemical or biophysical prediction and preventative measures. If these efforts fail, then the approach may have to be reactive using tocolytics to inhibit spontaneous prete...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190329124214
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Heat shock proteins are powerful endogenous cytoprotective proteins which help cells to survive recurrent cellular stress events. Identifying the underlying molecular mechanisms and molecular targets is especially interesting since it may help to develop new therapeutic strategies for the treatment of diseas...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160519113339
更新日期:2016-01-01 00:00:00
abstract::Management of hypertension has evolved steadily through 25 years of major clinical trials results modifying both the definition of hypertension and clinical management strategies. Trials experience in heart failure is much less extensive given the far smaller therapeutic market and traditionally often followed on the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454504
更新日期:2003-01-01 00:00:00
abstract::Lipid markers are well established predictors of vascular disease. The most frequently measured lipid variables are total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides. In this review we consider the predictive value of these variables and other more specialis...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054367409
更新日期:2005-01-01 00:00:00
abstract::Marine fungi with their successful pharmacological effects were considered to be the treasure of ocean medicines concerning the striking ability of their secondary metabolites. Literature over literature has been published on fungi derived bioactive molecules to probe its therapeutic potential. Marine fungi have an im...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200728142244
更新日期:2020-07-28 00:00:00
abstract::The present review discusses the mechanism of late stent thrombosis and its distinction from restenosis and summarizes the advisory note issued by FDA on the proper usage of different treatments available for atherosclerosis. In light of the latest developments, a plethora of new stents have been and continue to be de...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208785294573
更新日期:2008-01-01 00:00:00
abstract::Alcohol dependence is a major disease burden of adults in modern society worldwide. There is no cure for alcohol dependence. In this study, we have examined the molecular targets of ethanol-induced toxicity in humans based on a systematic review of literature data and then discussed current and potential therapeutic t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210791034030
更新日期:2010-01-01 00:00:00
abstract::The understanding of cytokine networks and the exploitation of these networks for the treatment of immune and inflammatory diseases as well as cancer depend on in vivo delivery of cytokines. Due to instability of recombinant cytokine proteins, investigators have employed cytokine-encoding gene therapy vectors to induc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003400551
更新日期:2000-04-01 00:00:00
abstract::There is growing evidence for the involvement of glutamatergic abnormalities in schizophrenia. Uncompetitive NMDA receptor (NMDAR) antagonists induce effects closely resembling both the positive and negative symptoms of schizophrenia; candidate risk genes for schizophrenia converge on the NMDAR expressing synapse; and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788957438
更新日期:2009-01-01 00:00:00
abstract::Reactive oxygen species (ROS), as well as reactive nitrogen species (RNS) play either harmful or beneficial role in biological systems. Beneficial effects of ROS include physiological roles in cellular responses against infectious agents and in several cellular signalling pathways. Harmful effects are due to high conc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789058084
更新日期:2009-01-01 00:00:00
abstract::Separating emotions from cognition seems impossible in everyday experiences of a human being. Emotional processes have an impact on the ability of planning and solving problems, or decision-making skills. They are a valuable source of information about ourselves, our partners in interactions and the surrounding world....
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151230110738
更新日期:2016-01-01 00:00:00
abstract::Rapid increase in the emergence and spread of microbes resistant to conventionally used antibiotics has become a major threat to global health care. Antimicrobial peptides (AMPs) are considered as a potential source of novel antibiotics because of their numerous advantages such as broad-spectrum activity, lower tenden...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990003
更新日期:2013-01-01 00:00:00
abstract::Active pharmaceutical ingredients (APIs) can exist in different polymorphic forms as well as in amorphous state. Polymorphic and amorphous forms of APIs can differ in physicochemical properties which in turn can significantly influence their therapeutic safety and effectiveness of the treatment. This review focuses on...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160804100036
更新日期:2016-01-01 00:00:00
abstract::Prion diseases are fatal neurodegenerative disorders associated with conformational conversion of the cellular prion protein (PrP(C)) into an isoform designated PrP(Sc). The pathogenic mechanism that links this conformational distortion with the development of prion diseases is unknown. PrP(C) is a GPI-anchored cell s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777698873
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:The last few decades have witnessed enormous advancements in the field of Pharmaceutical drug, design and delivery. One of the recent developments is the advent of 3DP technology. It has earlier been successfully employed in fields like aerospace, architecture, tissue engineering, biomedical research, medica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666181130163027
更新日期:2018-01-01 00:00:00
abstract::The purpose of this study is to answer the following question: What are the typical features of abnormal bodily experiences (ABEs) in persons affected by acute first-episode schizophrenia? Our overall objective is to contribute to enhance early diagnosis of schizophrenia, and providing supplementary diagnostic criteri...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212799316181
更新日期:2012-01-01 00:00:00
abstract::Oncology remains an increasingly important focus of therapeutic development yet there remain many scientific and operational bottlenecks to deliver optimum treatments efficiently. Radiopharmaceuticals constitute a group of methodologies able to support the many stages of drug development. Methods such as [(18)F]-FDG-P...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787581977
更新日期:2009-01-01 00:00:00
abstract::Catheter ablation for rhythm control in atrial fibrillation has been recognized as an established treatment. Patients with atrial fibrillation suffer from an increased risk of thromboembolic events. Long-term stroke risk and mortality have been shown to be reduced after catheter ablation, still the procedure per se is...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161205115101
更新日期:2017-01-01 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:BACKGROUND:Nuts have been an indispensable component of the human diet for hundreds because of their unique nutrient composition and are thought to play a beneficial part in the prevention of cardiovascular diseases. OBJECTIVE:To evaluate the extent, validity and presence of evidence for studies investigating the impa...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,meta分析,评审
doi:10.2174/1381612822666161010121356
更新日期:2017-01-01 00:00:00
abstract::Free energy simulations are a powerful tool to study molecular recognition. The most rigorous variants can provide in depth understanding for a particular system, but are not suited for high throughput application to large libraries of compounds. Related, but less expensive methods are increasingly popular, including ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319230008
更新日期:2013-01-01 00:00:00