Abstract:
:Protein Kinase Inhibitors (PKIs) and Histone Deacetylase Inhibitors (HDACIs) are two important classes of anticancer agents and have provided a variety of small molecule drugs for the treatment of various types of human cancers. However, malignant tumors are of a multifactorial nature that can hardly be "cured" by targeting a single target, and treatment of cancers hence requires modulation of multiple biological targets to restore the physiological balance and generate sufficient therapeutic efficacy. Multi-target drugs have attracted great interest because of their advantages in the treatment of complex cancers by simultaneously targeting multiple signaling pathways and possibly leading to synergistic effects. Synergistic effects have been observed in the combination of kinase inhibitors, such as imatinib, dasatinib, or sorafenib, with an array of HDACIs including vorinostat, romidepsin, or panobinostat. A considerable number of multi-target agents based on PKIs and HDACIs have been developed. In this review, we summarize the recent literature on the development of multi-target kinase-HDAC inhibitors and provide our view on the challenges and future directions on this topic.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Ling Y,Liu J,Qian J,Meng C,Guo J,Gao W,Xiong B,Ling C,Zhang Ydoi
10.2174/0929867327666200102115720subject
Has Abstractpub_date
2020-01-01 00:00:00pages
7264-7288issue
42eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-103411journal_volume
27pub_type
杂志文章abstract::Currently, the long-term usage of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in HIVAIDS patients eventually leads to the development of drug resistance and severe side effect. Therefore, it is imperative to look for the novel NNRTIs with potent and broad spectrum anti-mutant activity that are also safe a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709788803231
更新日期:2009-01-01 00:00:00
abstract::Poly(aminoester) dendrimers are expected to hold great promise as biodegradable nanocarriers for drug delivery due to their advantageous properties allowing their biodegradability, potentially lower toxicity and possibility of diverse chemical conjugations. The synthetic strategies for constructing such dendrimers inc...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867311209025011
更新日期:2012-01-01 00:00:00
abstract::Photodynamic therapy (PDT) is a novel medical technique involving three key components: light, a photosensitizer molecule and molecular oxygen, which are essential to achieve the therapeutic effect. There has been great interest in the use of PDT in the treatment of many cancers and skin disorders. Upon irradiation wi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867321666140826120300
更新日期:2014-01-01 00:00:00
abstract::Nanomedicine is certainly one of the scientific and technological challenges of the coming years. In particular, biodegradable nanoparticles formulated from poly (D,L-lactide-co-glycolide) (PLGA) have been extensively investigated for sustained and targeted delivery of different agents, including recombinant proteins,...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867311320170006
更新日期:2013-01-01 00:00:00
abstract::Agents modulating apoptosis are of extraordinary promise for the treatment of several states of disease including cancer, AIDS, neurodegenerative and ischemic diseases. In this review a brief summary of cellular pathways relevant to programmed cell death first is given and potential therapeutic targets therein are emp...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1999-05-01 00:00:00
abstract::ATP-sensitive K(+) channels (K(ATP)channels) regulate insulin secretion by coupling intracellular metabolic changes to excitability of the plasma membrane in pancreatic beta-cells. The channels are closed when extracellular glucose levels are elevated due to enhanced feature. By contrast, cardiac-type K(ATP) channels,...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033368475
更新日期:2003-02-01 00:00:00
abstract::Gene expression profiles are unveiling a wealth of new potential drug targets for a wide range of diseases, offering new opportunities for drug discoveries. The emerging challenge, however, is the effective selection of the myriad of targets to identify those with the most therapeutic utility. Numerical clustering has...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867053764626
更新日期:2005-01-01 00:00:00
abstract::Mitochondria are organelles which play an important role not only in cellular metabolism but also in controlling pathways related with cell death, ionic and redox regulation. Alterations in mitochondrial metabolism are implicated in a variety of diseases, including cancer. Cellular and mitochondrial metabolism are bot...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867322666150209155957
更新日期:2015-01-01 00:00:00
abstract::About 2.3% of the world's population is infected with hepatitis C virus (HCV) and patients have a high risk of developing liver cirrhosis and its complications. Current therapeutic strategies are based on a combination of pegylatedinterferon, ribavirin and (only for patients with genotype 1 infection) a protease inhib...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867321666140706125950
更新日期:2014-01-01 00:00:00
abstract::The stilbene scaffold is a basic element for a number of biologically active natural and synthetic compounds, and it is considered as a privileged structure. Stilbenes exemplified by resveratrol, combretastatin A-4 and pterostilbene are of significant interest for drug research and development because of their potenti...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666160517121629
更新日期:2016-01-01 00:00:00
abstract::Resistance to quinolones and fluoroquinolones has been increasingly reported among human and veterinary isolates during the last three decades related to their wide clinical use. Until recently, the mechanisms of resistance to quinolones in Enterobacteriaceae were believed to be only chromosome-encoded, i.e. related t...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709787581879
更新日期:2009-01-01 00:00:00
abstract::The development of new drugs with potential therapeutic applications is one of the most complex and difficult process in the pharmaceutical industry. Millions of dollars and man-hours are devoted to the discovery of new therapeutical agents. As, the activity of a drug is the result of a multitude of factors such as bi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867003375317
更新日期:2000-02-01 00:00:00
abstract::Reprogramming technologies have been developed to revert somatic differentiated cells into pluripotent stem cells that can be differentiated into different lineages potentially useful in stem cell therapy. Reprogramming methods have been progressively refined to increase their efficiency, to obtain a cell population s...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867321666131129125624
更新日期:2014-01-01 00:00:00
abstract::Epigenetics is a field of biological sciences focused on the study of reversible, heritable changes in gene function not due to modifications of the genomic sequence. These changes are the result of a complex cross-talk between several molecular mechanisms, that is in turn orchestrated by genetic and environmental fac...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867327666201117142006
更新日期:2020-11-17 00:00:00
abstract::Evidence indicates that nerve gas toxins operate in ways in addition to inhibition of acetylcholine esterase. Alternative bioactivities are discussed with focus on electron transfer. The main class, including pralidoxime (2-PAM), incorporates conjugated iminium and oxime moieties that are electron affinic. Various phy...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033456314
更新日期:2003-12-01 00:00:00
abstract::The cellular response to DNA damage is critical for determining whether carcinogenesis, cell death or other deleterious biological effects will ensue. Numerous cellular enzymatic mechanisms can directly repair damaged DNA, or allow tolerance of DNA lesions, and thus reduce potential harmful effects. These processes in...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708783497328
更新日期:2008-01-01 00:00:00
abstract::5-Aminoisoquinolin-1-one (5-AIQ) is a water-soluble inhibitor of the poly(ADPribose) polymerases (PARPs), lacking isoform-selectivity. Although of only moderate potency in vitro against PARP-1, it is highly active in many assays in cells and in models in vivo, indicating excellent uptake. Optimisation of the several s...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867322666151002110602
更新日期:2015-01-01 00:00:00
abstract::Coumarins are of many different structures. They constitute an important class of pharmacological agents possessing a range of different physiological activities including anti-cancer, anti-oxidant, anti- inflammation, anti-HIV, anti-coagulant, anti-bacterial, analgesic and comparative immune-modulation. Recently, cou...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709789578187
更新日期:2009-01-01 00:00:00
abstract::The use of dopaminergic agonists is key in the treatment of Parkinson's disease and related central nervous system (CNS) neurodegenerative disorders. Despite there are a number of commercialized dopaminergic agonists that are currently being used successfully in the first stages of the disease, they often fail to prov...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867323666160504103621
更新日期:2016-01-01 00:00:00
abstract::Acyclic nucleoside analogues bearing phosphonomethoxy residues in the side chain (ANP) attract much attention due to a very beneficial combination of biological properties. Intensive work of organic chemists during the last two decades resulted in a large panel of new compounds that were evaluated as potential antivir...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706778521896
更新日期:2006-01-01 00:00:00
abstract::Both zinc and copper are essential minerals that are required for various cellular functions. Although these metals are essential, they can be toxic at excess amounts, especially in certain genetic disorders. Zinc and copper homeostasis results from a coordinated regulation by different proteins involved in uptake, ex...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986705774462950
更新日期:2005-01-01 00:00:00
abstract::The fibrinolytic system includes a broad spectrum of proteolytic enzymes with physiological and pathophysiological functions in several processes, such as haemostatic balance, tissue remodeling, tumor invasion, angiogenesis and reproduction. The main enzyme of the plasminogen activator system is plasmin, which is resp...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708783955455
更新日期:2008-01-01 00:00:00
abstract::The calcium ion is quite possibly the single most pervasive signaling molecule used by living organisms for the purpose of communicating internal and external states. It differs from other messengers in that it is neither created nor destroyed, but just moved around inside and outside the cell via transporters, pumps ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712804143286
更新日期:2012-01-01 00:00:00
abstract::Matrix metalloproteinase-9 (MMP-9) plays an important role in the onset and prognosis of myocardial infarction. Targets of angiotensin converting enzyme (ACE) inhibitors might include not only ACE but also MMP-9, and ACE seems to be closely associated with complications of hypertension such as cardiovascular remodelin...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/092986709787846514
更新日期:2009-01-01 00:00:00
abstract::Chemoprevention is based on the use of non-toxic, pharmacologically active agents to prevent tumor progression. In this regard, natural dietary agents have been described by the most recent literature as promising tools for controlling onset and progression of malignancies. Extensive research has been so far performed...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867325666180629153141
更新日期:2020-01-01 00:00:00
abstract::Stress or heat shock proteins (Hsps) Hsp90, Hsp70 and Hsp27 are chaperones that assist the proteins in their folding, stability, assembly into multi-protein complexes and transport across cellular membranes. The expression of some of them is highly induced in response to a wide variety of physiological and environment...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707782360079
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Since Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor which plays an important role in multiple aspects of cancer, including progression and migration, and it is constitutively activated in various human tumors, STAT3 inhibition has emerged as a validated strategy for the...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180719122729
更新日期:2019-01-01 00:00:00
abstract::Anthocyanins are generally considered to be the largest and the most important group of water-soluble pigments in plants. They are widely consumed by humans as natural compounds of vegetables, fruits, and red wine. Anthocyanins as well as other flavonoids show protective qualities against variety of pathologies, inclu...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/09298673113209990153
更新日期:2013-01-01 00:00:00
abstract::Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It can occur at any age, however, it becomes extremely common in the elderly, with a prevalence approaching more than 20% in patients older than 85 years. AF is associated with a wide range of cardiac and extra-cardiac complications and there...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711796642373
更新日期:2011-01-01 00:00:00
abstract::In situ hybridization (ISH) is a type of hybridization that uses a labeled complementary DNA or RNA strand to localize a specific DNA or RNA sequence on a chromosome or section of tissue (in-situ) fixed on a slide. Flourescence in-situ hybridization (FISH) technique facilitates the localization of genes to different c...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712801661031
更新日期:2012-01-01 00:00:00